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Zolezzi DM, Kold S, Brock C, Jensen ABH, Jensen ST, Larsen IM, Olesen SS, Mørch CD, Drewes AM, Graven-Nielsen T. Transcranial Direct Current Stimulation Reduces Pressure Pain Sensitivity in Patients With Noncancer Chronic Pain. Clin J Pain 2024; 40:625-634. [PMID: 39310962 DOI: 10.1097/ajp.0000000000001246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 09/09/2024] [Indexed: 11/10/2024]
Abstract
OBJECTIVES Noncancer chronic pain is a clinical challenge because pharmacological treatment often fails to relieve pain. Transcranial direct current stimulation (tDCS) is a treatment that could have the potential for pain relief and improvement in quality of life. However, there is a lack of clinical trials evaluating the effects of tDCS on the pain system. The aim of the present study was to evaluate the effect of 5 days of anodal tDCS treatment on the pain system in patients with chronic noncancer pain using quantitative sensory testing and quality of life questionnaires: (1) Brief Pain Inventory-short form, (2) European Organization for Research and Treatment of Life Questionnaire-C30, and (3) Hospital Anxiety Depression Scale. METHODS Eleven patients with noncancer chronic pain (51 ± 13.6 y old, 5M) participated in the study. Anodal tDCS was applied for 5 consecutive days, followed by sham stimulation after a washout period of at least 2 weeks. Pressure pain thresholds and pain tolerance thresholds (PTT) were assessed in different body regions on days 1 and 5. RESULTS Anodal tDCS appeared to maintain PTT at C5 (clavicle) on day 5, but sham stimulation decreased PTT ( P = 0.007). In addition, anodal tDCS increased PTT compared with sham at day 5 at Th10 ventral dermatomes ( P = 0.014). Both anodal and sham tDCS decreased the Brief Pain Inventory-short form total and interference scores, and the European Organization for Research and Treatment of Life Questionnaire-C30 fatigue score, but no interaction effect was observed. CONCLUSION This study adds to the evidence in the literature that tDCS may be a potential therapeutic tool for the management of noncancer chronic pain.
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Affiliation(s)
- Daniela M Zolezzi
- Department of Health Science and Technology, Center for Neuroplasticity and Pain (CNAP), Aalborg University, Aalborg, Denmark, Gistrup
| | - Sebastian Kold
- Department of Health Science and Technology, Center for Neuroplasticity and Pain (CNAP), Aalborg University, Aalborg, Denmark, Gistrup
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Anne Birthe Helweg Jensen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Sarah Thorius Jensen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | | | - Søren Schou Olesen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Carsten Dahl Mørch
- Department of Health Science and Technology, Center for Neuroplasticity and Pain (CNAP), Aalborg University, Aalborg, Denmark, Gistrup
| | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Thomas Graven-Nielsen
- Department of Health Science and Technology, Center for Neuroplasticity and Pain (CNAP), Aalborg University, Aalborg, Denmark, Gistrup
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Chen KY, Chan HC, Wei LY, Chan CM. Efficacy of gabapentin and pregabalin for treatment of post refractive surgery pain: a systematic review and meta-analysis. Int Ophthalmol 2024; 44:409. [PMID: 39448432 DOI: 10.1007/s10792-024-03300-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 08/28/2024] [Indexed: 10/26/2024]
Abstract
INTRODUCTION For ophthalmic patients, eye discomfort is a major problem that requires efficient pain treatment techniques. Pregabalin and gabapentin have surfaced as viable treatments for post-refractive surgery pain. To manage pain after refractive surgery, gabapentin and pregabalin were evaluated in this systematic review and meta-analysis. METHODOLOGY A thorough search of databases including PubMed, Embase, Cochrane Library, and CINAHL was performed until March 2024. Inclusion criteria were randomized controlled trials assessing pregabalin and/or gabapentin's effectiveness in treating pain post-PRK, LASIK, and LASEK surgeries. RESULTS Six studies met inclusion criteria, comprising a total of 391 patients undergoing various corneal surgeries. The meta-analysis revealed that pregabalin was significantly more effective than placebo in reducing pain on the first and second postoperative days (SMD day 1: -0.32, 95% CI -0.54, -0.09; SMD day 2: -0.55, 95% CI -0.85, -0.25), while gabapentin showed significant pain reduction on the second day only (SMD day 2: -0.42, 95% CI -0.71, -0.13). Combined analysis for both medications showed significant pain reduction on the first- and second-days post-surgery. No significant increase in adverse events was associated with either medication. Publication bias was minimal except for a slight asymmetry noted on day 1 effectiveness. CONCLUSION Pregabalin and gabapentin are effective in reducing postoperative pain following refractive surgeries, with pregabalin showing a greater effect. Both medications are safe, with no significant increase in adverse events. Further research with standardized methodologies and long-term follow-up is recommended to optimize postoperative pain management in ocular surgeries.
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Affiliation(s)
- Kai-Yang Chen
- School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Hoi-Chun Chan
- School of Pharmacy, China Medical University, Taichung, Taiwan
| | - Li-Yun Wei
- Department of Pharmacy, Cardinal Tien Hospital, New Taipei City, Taiwan.
| | - Chi-Ming Chan
- Department of Ophthalmology, Cardinal Tien Hospital, New Taipei City, Taiwan.
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
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Wilcox CM, Bang JY, Buxbaum J, Gardner TB, Hawes R, Kedia P, Mardini SH, Muniraj T, Navaneethan U, Oza VM, Tarnasky P, Thakkar S, Waxman I, Varadarajulu S. Effect of endoscopic ultrasound guided celiac plexus block on the palliation of pain in chronic pancreatitis (EPOCH Trial): study protocol for a randomized multicenter sham-controlled trial {1}. Trials 2024; 25:676. [PMID: 39396987 PMCID: PMC11472533 DOI: 10.1186/s13063-024-08478-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Accepted: 09/17/2024] [Indexed: 10/15/2024] Open
Abstract
BACKGROUND Celiac plexus block has been commonly utilized for the treatment of chronic pancreatitis-associated abdominal pain. Prospective studies suggest efficacy in 30 to 50% of patients, although no randomized sham-controlled trials have been performed. The objective of this study is to assess the effect of endoscopic ultrasound (EUS)-guided celiac plexus block on abdominal pain in patients with documented chronic pancreatitis. METHODS This is a two-arm randomized sham-controlled trial with blinded evaluators. The study will be conducted at multiple academic sites in the United States who are members of the United States Pancreatic Disease Study Group (USPG). Patients referred for EUS to exclude chronic pancreatitis as a cause of abdominal pain as well as those with established painful chronic pancreatitis undergoing EUS for another indication will be eligible. At the time of EUS with confirmation of chronic pancreatitis by standard EUS diagnostic criteria, patients will be randomized to either celiac plexus block or sham whereby an anesthetic and steroid combination will be injected into the celiac plexus or saline will be injected into the gastric lumen with the same type of needle as used for celiac plexus block, respectively. The main outcome measure will be a 50% reduction in abdominal pain using the Brief Pain Inventory Short Form (BPI-SF) at 1 month post-intervention. A number of secondary outcomes will be measured including visual analog scale (VAS), Comprehensive Pain Assessment Tool Short Form (COMPAT-SF) pain scores, and quality of life using a pancreas-specific validated measure (PANQOLI). DISCUSSION In this study, the effect of celiac plexus block on abdominal pain in patients with chronic pancreatitis will be compared to a sham intervention. This randomized trial will offer a definitive assessment of the role of celiac plexus block for the treatment of abdominal pain in this setting. TRIAL REGISTRATION {2}: ClinicalTrials.gov NCT06178315. Registered on December 21, 2023.
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Affiliation(s)
- C Mel Wilcox
- Digestive Health Institute, Orlando Health, 1720 Orange Ave., Suite 200, Orlando, FL, 32806, USA.
| | - Ji Young Bang
- Digestive Health Institute, Orlando Health, 1720 Orange Ave., Suite 200, Orlando, FL, 32806, USA
| | | | | | - Robert Hawes
- Digestive Health Institute, Orlando Health, 1720 Orange Ave., Suite 200, Orlando, FL, 32806, USA
| | | | | | | | - Udayakumar Navaneethan
- Digestive Health Institute, Orlando Health, 1720 Orange Ave., Suite 200, Orlando, FL, 32806, USA
| | | | | | | | | | - Shyam Varadarajulu
- Digestive Health Institute, Orlando Health, 1720 Orange Ave., Suite 200, Orlando, FL, 32806, USA
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Jiang LY, Han C, Hu LH. Progress in treatment of chronic pancreatitis: A review based on the ClinicalTrials.gov database. Shijie Huaren Xiaohua Zazhi 2024; 32:635-644. [DOI: 10.11569/wcjd.v32.i9.635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 08/23/2024] [Accepted: 09/03/2024] [Indexed: 09/28/2024] Open
Abstract
Chronic pancreatitis (CP) is a chronic progressive fibro-inflammatory disease of the pancreas caused by various etiologies, characterized by recurrent upper abdominal pain and pancreatic exocrine dysfunction. ClinicalTrials.gov is the most commonly used clinical trial database, including information of clinical trials which have been completed or are ongoing, or upcoming. Based on the ClinicalTrials.gov database, we retrieved all clinical studies registered before June 30, 2024, screened out recent clinical studies related to CP, and summarized and integrated highlights and directions of these studies from the perspectives of nutritional support, medication, endoscopy, etc., aiming to provide new ideas for the design of CP clinical studies in the future.
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Affiliation(s)
- Ling-Ying Jiang
- School of Basic Medicine, Naval Medical University, Shanghai 200433, China
| | - Chao Han
- Hospital of 91876 Troops of Chinese People's Liberation Army, Qinhuangdao 066203, Hebei Province, China
- Department of Gastroenterology, Naval Medical Center, Naval Medical University, Shanghai 200052, China
| | - Liang-Hao Hu
- Department of Gastroenterology, First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
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5
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Starkweather AR, Xu W, Gnall KE, Emrich M, Garnsey CL, Magin ZE, Wu W, Fetta J, Groessl EJ, Park C. Testing Biological and Psychological Pathways of Emotion Regulation as a Primary Mechanism of Action in Yoga Interventions for Chronic Low Back Pain: Protocol for a Randomized Controlled Trial. JMIR Res Protoc 2024; 13:e56016. [PMID: 38483469 PMCID: PMC10979342 DOI: 10.2196/56016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 02/02/2024] [Accepted: 02/05/2024] [Indexed: 03/27/2024] Open
Abstract
BACKGROUND Interventions that promote adaptive emotion regulation (ER) skills reduce pain in patients with chronic pain; however, whether the effects of yoga practice on chronic low back pain (CLBP) are due to improvements in ER remains to be examined. OBJECTIVE This study will test whether the effects of yoga on CLBP (improved pain severity and interference) are mediated by improved ER, the extent to which effects are related to specific aspects of ER, and the role of pain sensitization as a mediator or moderator of effects. In this study, pain sensitization will be assessed by quantitative sensory testing and gene expression profiles to examine whether pain sensitization moderates yoga's effects on pain or whether yoga and ER abilities reduce pain sensitization, leading to decreased pain severity and interference. METHODS For this 2-arm parallel group blinded randomized controlled trial, we will enroll 204 adults with CLBP who will be randomized to receive the yoga (n=102) or a control stretching and strengthening (n=102) intervention, which are delivered via web-based synchronous biweekly 75-minute sessions over 12 weeks. Participants are encouraged to practice postures or exercises for 25 minutes on other days using accessible prerecorded practice videos that are sent to participants digitally. Participants will be assessed at 5 time points: baseline, midintervention (6 weeks), postintervention (12 weeks), and 3- and 6-month follow-ups. Assessments of ER, pain severity and interference, pain sensitivity including somatosensory and gene expression profiles, and physical strength and flexibility will be conducted at each visit. The fidelity of the interventions is assessed using a manualized checklist to evaluate recorded group sessions to ensure consistent instructor delivery. RESULTS The primary outcome will be the mean change in pain severity as measured by the Brief Pain Inventory-Short Form at 12 weeks. The primary mechanism of action is ER measured by change in the Difficulties in Emotion Regulation Scale total score. Secondary outcomes include pain sensitivity, physical strength and flexibility, pain interference, and quality of life. A mediation path analysis and series of moderated mediation path analyses will be conducted to test the study hypotheses. As of January 2024, we have enrolled 138 participants. We expect the study to be completed by May 2025. CONCLUSIONS The study will provide important data for evaluating whether improvements in ER are responsible for reduced pain perception and pain sensitivity as well as increased quality of life in the context of chronic pain. The study findings have important implications for determining the mechanism of action for yoga and possibly other mind-body interventions as nonpharmacological therapies for pain management. The results of the study will inform the content, delivery, and measures for intervention trials involving yoga as a modality for relieving pain and improving function. TRIAL REGISTRATION ClinicalTrials.gov NCT04678297; https://clinicaltrials.gov/study/NCT04678297. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/56016.
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Affiliation(s)
- Angela R Starkweather
- Department of Biobehavioral Nursing Science, College of Nursing, University of Florida, Gainesville, FL, United States
| | - Wanli Xu
- School of Nursing, University of Connecticut, Storrs, CT, United States
| | - Katherine E Gnall
- Department of Psychological Sciences, University of Connecticut, Storrs, CT, United States
| | - Mariel Emrich
- Department of Psychological Sciences, University of Connecticut, Storrs, CT, United States
| | - Camille L Garnsey
- Department of Psychological Sciences, University of Connecticut, Storrs, CT, United States
| | - Zachary E Magin
- Department of Psychological Sciences, University of Connecticut, Storrs, CT, United States
| | - Weizi Wu
- School of Nursing, University of Connecticut, Storrs, CT, United States
| | - Joseph Fetta
- Department of Biobehavioral Nursing Science, College of Nursing, University of Florida, Gainesville, FL, United States
| | - Erik J Groessl
- Herbert Wertheim School of Public Health & Human Longevity Science, University of California San Diego, San Diego, CA, United States
- Veteran's Affairs San Diego Health System, San Diego, CA, United States
| | - Crystal Park
- Department of Psychological Sciences, University of Connecticut, Storrs, CT, United States
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6
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Walker J, Babyok OL, Saloman JL, Phillips AE. Recent advances in the understanding and management of chronic pancreatitis pain. JOURNAL OF PANCREATOLOGY 2024; 7:35-44. [PMID: 38524856 PMCID: PMC10959534 DOI: 10.1097/jp9.0000000000000163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 12/09/2023] [Indexed: 03/26/2024] Open
Abstract
Abdominal pain is the most common symptom of chronic pancreatitis (CP) and is often debilitating for patients and very difficult to treat. To date, there exists no cure for the disease. Treatment strategies focus on symptom management and on mitigation of disease progression by reducing toxin exposure and avoiding recurrent inflammatory events. Traditional treatment protocols start with medical management followed by consideration of procedural or surgical intervention on selected patients with severe and persistent pain. The incorporation of adjuvant therapies to treat comorbidities including psychiatric disorders, exocrine pancreatic insufficiency, mineral bone disease, frailty, and malnutrition, are in its early stages. Recent clinical studies and animal models have been designed to improve investigation into the pathophysiology of CP pain, as well as to improve pain management. Despite the array of tools available, many therapeutic options for the management of CP pain provide incomplete relief. There still remains much to discover about the neural regulation of pancreas-related pain. In this review, we will discuss research from the last 5 years that has provided new insights into novel methods of pain phenotyping and the pathophysiology of CP pain. These discoveries have led to improvements in patient selection for optimization of outcomes for both medical and procedural management, and identification of potential future therapies.
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Affiliation(s)
- Jessica Walker
- Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Olivia L. Babyok
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
| | - Jami L. Saloman
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
- Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
| | - Anna Evans Phillips
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
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Han C, Lv YW, Hu LH. Management of chronic pancreatitis: recent advances and future prospects. Therap Adv Gastroenterol 2024; 17:17562848241234480. [PMID: 38406795 PMCID: PMC10894541 DOI: 10.1177/17562848241234480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 01/30/2024] [Indexed: 02/27/2024] Open
Abstract
As a progressive fibroinflammatory disease, chronic pancreatitis (CP) often manifests as recurrent bouts of abdominal pain with or without complications, causing a heavy burden of health care. In recent years, some meaningful insights into the management of CP have been obtained from randomized controlled trials, systematic reviews, and meta-analyses, which were of great importance. Based on this research, it is shown that there are various treatments for CP. Therefore, it is of great importance to choose a suitable strategy for patients with CP individually. Relevant evidence on the management of CP was summarized in this review, including nutrition supplements, medication, endoscopy, surgery, exploration of novel therapies as well as evaluation and prediction of treatment response.
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Affiliation(s)
- Chao Han
- Department of Gastroenterology, The Hospital of 91876 Troops of Chinese People’s Liberation Army, Qinhuangdao, China
| | - Yan-Wei Lv
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
- Shanghai Institute of Pancreatic Diseases, Shanghai, China
| | - Liang-Hao Hu
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, 168 Changhai Road, Shanghai 200433, China
- National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China
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8
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Edwards RR, Schreiber KL, Dworkin RH, Turk DC, Baron R, Freeman R, Jensen TS, Latremoliere A, Markman JD, Rice ASC, Rowbotham M, Staud R, Tate S, Woolf CJ, Andrews NA, Carr DB, Colloca L, Cosma-Roman D, Cowan P, Diatchenko L, Farrar J, Gewandter JS, Gilron I, Kerns RD, Marchand S, Niebler G, Patel KV, Simon LS, Tockarshewsky T, Vanhove GF, Vardeh D, Walco GA, Wasan AD, Wesselmann U. Optimizing and Accelerating the Development of Precision Pain Treatments for Chronic Pain: IMMPACT Review and Recommendations. THE JOURNAL OF PAIN 2023; 24:204-225. [PMID: 36198371 PMCID: PMC10868532 DOI: 10.1016/j.jpain.2022.08.010] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 08/01/2022] [Accepted: 08/17/2022] [Indexed: 11/06/2022]
Abstract
Large variability in the individual response to even the most-efficacious pain treatments is observed clinically, which has led to calls for a more personalized, tailored approach to treating patients with pain (ie, "precision pain medicine"). Precision pain medicine, currently an aspirational goal, would consist of empirically based algorithms that determine the optimal treatments, or treatment combinations, for specific patients (ie, targeting the right treatment, in the right dose, to the right patient, at the right time). Answering this question of "what works for whom" will certainly improve the clinical care of patients with pain. It may also support the success of novel drug development in pain, making it easier to identify novel treatments that work for certain patients and more accurately identify the magnitude of the treatment effect for those subgroups. Significant preliminary work has been done in this area, and analgesic trials are beginning to utilize precision pain medicine approaches such as stratified allocation on the basis of prespecified patient phenotypes using assessment methodologies such as quantitative sensory testing. Current major challenges within the field include: 1) identifying optimal measurement approaches to assessing patient characteristics that are most robustly and consistently predictive of inter-patient variation in specific analgesic treatment outcomes, 2) designing clinical trials that can identify treatment-by-phenotype interactions, and 3) selecting the most promising therapeutics to be tested in this way. This review surveys the current state of precision pain medicine, with a focus on drug treatments (which have been most-studied in a precision pain medicine context). It further presents a set of evidence-based recommendations for accelerating the application of precision pain methods in chronic pain research. PERSPECTIVE: Given the considerable variability in treatment outcomes for chronic pain, progress in precision pain treatment is critical for the field. An array of phenotypes and mechanisms contribute to chronic pain; this review summarizes current knowledge regarding which treatments are most effective for patients with specific biopsychosocial characteristics.
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Affiliation(s)
| | | | | | - Dennis C Turk
- Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington
| | - Ralf Baron
- Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital Schleswig-Holstein, Arnold-Heller-Straße 3, House D, 24105 Kiel, Germany
| | - Roy Freeman
- Harvard Medical School, Boston, Massachusetts
| | | | | | | | | | | | | | | | | | - Nick A Andrews
- Salk Institute for Biological Studies, San Diego, California
| | | | | | | | - Penney Cowan
- American Chronic Pain Association, Rocklin, California
| | - Luda Diatchenko
- Department of Anesthesia and Faculty of Dentistry, McGill University, Montreal, California
| | - John Farrar
- University of Pennsylvania, Philadelphia, Pennsylvania
| | | | | | - Robert D Kerns
- Yale University, Departments of Psychiatry, Neurology, and Psychology, New Haven, Connecticut
| | | | | | - Kushang V Patel
- Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington
| | | | | | | | | | - Gary A Walco
- Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington
| | - Ajay D Wasan
- University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Ursula Wesselmann
- Department of Anesthesiology/Division of Pain Medicine, Neurology and Psychology, The University of Alabama at Birmingham, Birmingham, Alabama
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Muthulingam JA, Olesen SS, Hansen TM, Drewes AM, Frøkjær JB. White matter brain changes in chronic pancreatitis: A 7-year longitudinal follow-up study. Pancreatology 2022; 22:871-879. [PMID: 36031507 DOI: 10.1016/j.pan.2022.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 08/09/2022] [Accepted: 08/12/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES The progression of cerebral white matter changes over time has not been explored in chronic pancreatitis (CP). We aimed to characterize such alterations in individuals with CP at baseline and after 7-years as compared with controls and to explore associations to risk factors and clinical parameters. METHODS Diffusion tensor imaging was used to evaluate 20 individuals with CP and 13 healthy controls at baseline and after 7-years (CP: n = 9, controls: n = 11). Tract-based spatial statistics were used to assess whole-brain white matter structure, extract significant fractional anisotropy (FA) clusters between groups, mean FA skeleton, mean FA and mean diffusivity (MD). FA of the extracted significant clusters between groups were used for regression analyses with risk factors and clinical parameters, including duration of CP, smoking, and diabetes. RESULTS At baseline, widespread reductions in FA were found in CP compared to controls involving corpus callosum, the anterior, posterior thalamic radiation, and superior and posterior corona radiata (cluster volume: 49,431 mm3, all P < 0.05). At baseline, also the mean FA (P = 0.004) and FA skeleton (P = 0.002) were reduced in CP compared to controls. FA of the extracted significant cluster was associated with the daily tobacco use (P = 0.001) and duration of CP (P = 0.010). At follow-up, the whole-brain FA skeleton was reduced by 1.7% for both CP individuals and controls (P = 0.878). CONCLUSION Individuals with CP had widespread cerebral white matter alterations at baseline that can likely be explained by the CP disease and exposure to toxic substances. Otherwise, further progression resembles that in healthy controls.
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Affiliation(s)
- Janusiya Anajan Muthulingam
- Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Søren Schou Olesen
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Centre for Pancreatic Diseases, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark; Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Tine Maria Hansen
- Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Asbjørn Mohr Drewes
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Centre for Pancreatic Diseases, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Jens Brøndum Frøkjær
- Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
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10
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Sarkar S, Sarkar P, M R, Hazarika D, Prasanna A, Pandol SJ, Unnisa M, Jakkampudi A, Bedarkar AP, Dhagudu N, Reddy DN, Talukdar R. Pain, depression, and poor quality of life in chronic pancreatitis: Relationship with altered brain metabolites. Pancreatology 2022; 22:688-697. [PMID: 35710761 DOI: 10.1016/j.pan.2022.06.007] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 05/22/2022] [Accepted: 06/03/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND To evaluate if altered brain metabolites are connected to pain, depression and affective responses in CP. METHODS In this prospective study we evaluated pain characteristics, QOL (EORTC QLQc30+PAN28), depression (Beck depression inventory [BDI] II) in 558 patients with CP and 67 healthy controls. Brain metabolites were evaluated using magnetic resonance spectroscopy (MRS) in 49 patients and 5 healthy controls. We measured plasma metabolites using gas chromatography-mass spectrometry (GC-MS/MS). Relationship between metabolomic alterations, pain, depression and QOL components were assessed using statistical/bioinformatics methods. Benjamini-Hochberg FDR correction was applied for multiple testing. RESULTS 261 (46.8%) patients had depression compared to 5 (7.5%) among healthy controls [n = 67](p < 0.0001). Risk [OR (95% CI) of developing depression in the presence of pain was 1.9 (1.33-1.68); p = 0.0004. The depression scores correlated negatively with functional components and positively with symptom components of EORTC QLQ30. Significant negative correlation, though based on a small sample size, was observed between N-acetyl aspartate in the left hippocampus and choline in the left prefrontal cortex with emotional and cognitive functions. PLS-DA modelling revealed significant alteration in the plasma metabolomic profile among patients with CP who had depression. Six metabolites were significantly different between CP with depression and healthy controls, of which glycine contributed most significantly to the PLS-DA model (VIP score of 3.5). CONCLUSIONS A significant proportion of patients with CP develops depression that correlate with poor QOL functions. Pain, depression, and emotional components of QOL in patients with CP correlated with N-acetyl aspartate and choline in the left hippocampus and left prefrontal cortex of the brain.
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Affiliation(s)
- Subhaleena Sarkar
- Wellcome-DBT India Alliance Labs., Institute of Basic and Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology, Hyderabad, India
| | - Priyanka Sarkar
- Wellcome-DBT India Alliance Labs., Institute of Basic and Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology, Hyderabad, India
| | - Revanth M
- Department of Radiodiagnosis, Asian Institute of Gastroenterology, Hyderabad, India
| | - Dibyamohan Hazarika
- Department of Radiodiagnosis, Asian Institute of Gastroenterology, Hyderabad, India
| | - Ambika Prasanna
- Wellcome-DBT India Alliance Labs., Institute of Basic and Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology, Hyderabad, India
| | | | - Misbah Unnisa
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Aparna Jakkampudi
- Wellcome-DBT India Alliance Labs., Institute of Basic and Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology, Hyderabad, India
| | | | - Naveen Dhagudu
- Division of Psychiatry, Asian Institute of Gastroenterology, Hyderabad, India
| | - D Nageshwar Reddy
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Rupjyoti Talukdar
- Wellcome-DBT India Alliance Labs., Institute of Basic and Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology, Hyderabad, India; Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India.
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11
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van den Beukel BAW, de Ree R, van Goor H, van der Wal SEI, Ten Broek RPG. Analgesia in patients with adhesion-related chronic abdominal and pelvic pain after surgery: a systematic review. Acta Chir Belg 2022; 122:303-311. [PMID: 33899669 DOI: 10.1080/00015458.2021.1881336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
BACKGROUND AND OBJECTIVE Adhesions are the most common cause of chronic abdominal pain after surgery. Surgical adhesiolysis can relieve symptoms in selected patients, but many require other treatments. The aim of this study is to evaluate analgesic treatments other than abdominal surgery in chronic pain related to adhesions. DATABASE AND DATA TREATMENT A search was conducted in PubMed, Embase, and Central. Studies with patients suffering from chronic postoperative pain related to adhesions and undergoing all types' analgesic treatment were included. The primary outcome was the number of patients who improved in pain at long-term follow-up (at least 1 year). Secondary outcomes included improvement in pain at 3 months follow-up, quality of life, and physical functioning. RESULTS Searches identified 3022 citations. Four studies were included, one trial, one cohort study, and two case reports. The primary outcome was not reported. In a small trial (n = 18) pregabalin tended to have a benefit over placebo improving pain at 3 months. In the cohort study, 17 patients with chronic pelvic pain underwent a trial of sacral nerve stimulation. Eight patients who responded positively received an implanted device for continuous modulation, reporting sustainable improvement during follow-up (range: 6-36 months). One case report described improved pain at 6 months with trans-abdominis plane stimulation. The second report described improvement of physical function with manual therapy at long-term follow-up. CONCLUSIONS Low level of evidence is available regarding analgesic treatments of chronic abdominal and pelvic pain related to adhesions. The benefit of pregabalin is doubtful; nerve modulation is promising in a selected group.HighlightsAdhesions are a frequent cause of chronic abdominal and pelvic pain after surgery.Many patients are not good candidates for surgery (Adhesiolysis) or have relapses of pain.There is an important knowledge gap regarding non-surgical analgesic treatment.Analgesia in adhesion-related chronic abdominal pain after surgery.
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Affiliation(s)
- B A W van den Beukel
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - R de Ree
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - H van Goor
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - S E I van der Wal
- Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - R P G Ten Broek
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
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12
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Witkoś J, Fusińska-Korpik A, Hartman-Petrycka M, Nowak A. An assessment of sensory sensitivity in women suffering from depression using transcutaneous electrical nerve stimulation. PeerJ 2022; 10:e13373. [PMID: 35573182 PMCID: PMC9097666 DOI: 10.7717/peerj.13373] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 04/13/2022] [Indexed: 01/13/2023] Open
Abstract
Background Perception is the process or result of the process arising from the mental interpretation of the phenomena occurring, therefore it depends not only on physiology, but is also psychologically and socially conditioned. The aim of this study was to assess if there is a difference in the sensory sensitivity to an electrical stimulus in women suffering from depression and what the hedonic rating is of the lived experience of transcutaneous electrical nerve stimulation. Methods The depression group: 44 women, who were inpatients treated for depression at the Psychiatric Ward in the Clinical Hospital, and the control group: 41 women, matched by the age, height and weight, with no mental illness. Measures: threshold for sensing current, type of sensation evoked, hedonic rating. Results Median sensing threshold of electric current (depression vs. control: 7.75 mA vs. 8.35 mA; no significant), type of sensation evoked (depression vs. control: tingling 90.9% vs. 92.7%, no significant), hedonic rating (depression vs. control: unpleasant 11.4% vs. 2.4%; p = 0.003), hedonic rating (mildly ill vs. moderately ill vs. markedly ill: unpleasant 5.3% vs. 6.3% vs. 33.3%; p = 0.066). Conclusions Women suffering from depression exhibit a similar threshold of sensitivity to an electrical stimulus as mentally healthy women, however the hedonic rating of the stimulus acting on the skin in the group of clinically depressed women was more negative than in the mentally healthy subjects. The stimulus was described as 'unpleasant' for many of the mentally unhealthy women. The most negative sensations related to the electrical stimulus were experienced by women with the highest severity of mental illness according to The Clinical Global Impression - Severity Scale.
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Affiliation(s)
- Joanna Witkoś
- Medicine and Health Science, Andrzej Frycz Modrzewski Krakow University, Kraków, Poland
| | - Agnieszka Fusińska-Korpik
- Medicine and Health Science, Andrzej Frycz Modrzewski Krakow University, Kraków, Poland,Józef Babiński Clinical Hospital in Krakow, Psychiatric Ward, Kraków, Poland
| | - Magdalena Hartman-Petrycka
- Department of Basic Biomedical Science, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland
| | - Agnieszka Nowak
- Józef Babiński Clinical Hospital in Krakow, Psychiatric Ward, Kraków, Poland
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13
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Zafereo J, Uhlenbrock B, Watson S, Wang-Price S, Noe C, Jarrett RB, Meltzer KJ, Huang M. Using quantitative sensory testing to predict attrition in an interdisciplinary pain management program: a pilot study. Pain Manag 2022; 12:623-633. [PMID: 35345888 DOI: 10.2217/pmt-2021-0053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: To determine the extent to which quantitative sensory testing (QST) predicted attrition in an interdisciplinary pain program (IPP). Patients & methods: Participants (n = 53) enrolled in an IPP completed pretreatment assessments of QST and the PROMIS-29 quality of life survey. Results & conclusion: Compared with completers, non-completers (24.5%) reported significantly higher pain intensity (7.1, 95% CI [5.8, 8.4] versus 5.4, 95% CI [4.8, 6.1]) and cold hyperalgesia (14.6°C, 95% CI [8.8, 20.4] versus 7.5°C, 95% CI [4.8, 6.1]), with both variables also predicting attrition. This finding highlights a potentially novel and clinically significant use of QST. Higher overall pain intensity and the presence of remote cold hyperalgesia may identify patients at risk for dropping out of an IPP.
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Affiliation(s)
- Jason Zafereo
- Department of Physical Therapy, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Brittany Uhlenbrock
- Department of Physical Therapy, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Seth Watson
- School of Physical Therapy, Texas Woman's University, Dallas, TX 75235, USA
| | - Sharon Wang-Price
- School of Physical Therapy, Texas Woman's University, Dallas, TX 75235, USA
| | - Carl Noe
- Department of Anesthesiology & Pain Management, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Robin B Jarrett
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Karen J Meltzer
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Mu Huang
- Department of Applied Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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14
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Abstract
Managing chronic pain remains a major unmet clinical challenge. Patients can be treated with a range of interventions, but pharmacotherapy is the most common. These include opioids, antidepressants, calcium channel modulators, sodium channel blockers, and nonsteroidal anti-inflammatory drugs. Many of these drugs target a particular mechanism; however, chronic pain in many diseases is multifactorial and induces plasticity throughout the sensory neuroaxis. Furthermore, comorbidities such as depression, anxiety, and sleep disturbances worsen quality of life. Given the complexity of mechanisms and symptoms in patients, it is unsurprising that many fail to achieve adequate pain relief from a single agent. The efforts to develop novel drug classes with better efficacy have not always proved successful; a multimodal or combination approach to analgesia is an important strategy in pain control. Many patients frequently take more than one medication, but high-quality evidence to support various combinations is often sparse. Ideally, combining drugs would produce synergistic action to maximize analgesia and reduce side effects, although sub-additive and additive analgesia is still advantageous if additive side-effects can be avoided. In this review, we discuss pain mechanisms, drug actions, and the rationale for mechanism-led treatment selection.Abbreviations: COX - cyclooxygenase, CGRP - calcitonin gene-related peptide, CPM - conditioned pain modulation, NGF - nerve growth factor, NNT - number needed to treat, NMDA - N-methyl-d-aspartate, NSAID - nonsteroidal anti-inflammatory drugs, TCA - tricyclic antidepressant, SNRI - serotonin-noradrenaline reuptake inhibitor, QST - quantitative sensory testing.
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Affiliation(s)
- Ryan Patel
- Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, UK
| | - Anthony H Dickenson
- Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, UK
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15
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Assessment of pain associated with chronic pancreatitis: An international consensus guideline. Pancreatology 2021; 21:1256-1284. [PMID: 34391675 DOI: 10.1016/j.pan.2021.07.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 07/16/2021] [Accepted: 07/16/2021] [Indexed: 12/11/2022]
Abstract
Pain is the most common symptom in chronic pancreatitis (CP) with a major impact on quality of life. Few validated questionnaires to assess pain in CP exist, and the lack of consensus negatively impacts clinical management, research and meta-analysis. This guideline aims to review generic pain questionnaires for their usability in CP, to outline how pain assessment can be modified by confounding factors and pain types, to assess the value of additional measures such as quality of life, mental health and quantitative sensory testing, and finally to review pain assessment questionnaires used specifically in CP. A systematic review was done to answer 27 questions that followed the PICO (Population; Intervention; Comparator; Outcome) template. Quality of evidence of the statements was judged by Grades of Recommendation, Assessment, Development and Evaluation (GRADE) criteria. The manuscript was sent for review to 36 experts from various disciplines and continents in a multi-stage Delphi process, and finally reviewed by patient representatives. Main findings were that generic pain instruments are valid in most settings, but aspects of pain are specific for CP (including in children), and instruments have to account for the wide phenotypic variability and development of sensitization of the central nervous system. Side effects to treatment and placebo effects shall also be considered. Some multidimensional questionnaires are validated for CP and are recommended together with assessment of quality of life and psychiatric co-morbidities. This guideline will result in more homogeneous and comprehensive pain assessment to potentially improve management of painful CP.
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16
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Yang Z, Wang T, Hu LH. Progress in pharmacotherapy for alleviating pain of chronic pancreatitis. Shijie Huaren Xiaohua Zazhi 2021; 29:217-222. [DOI: 10.11569/wcjd.v29.i5.217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Pain is the main clinical symptom of chronic pancreatitis (CP), as well as the most common cause of patients' recurrent hospitalizations. The management regimen for CP pain needs to be formulated according to the patient's conditions. Lifestyle changes and drug treatment can usually be used as first-line therapy. Conventional analgesics, pancreatic enzymes, and antioxidants are commonly used in treating pain of CP. In recent years, the application of conventional analgesics has been further standardized. Besides, there have been more clinical studies on the treatment of CP pain with pancreatic enzymes or antioxidants. Traditional Chinese medicine has played an increasingly important role in the treatment of CP pain. New drugs such as camostat mesylate are expected to be used in CP pain, though more high-quality studies are still needed to confirm their safety and effectiveness.
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Affiliation(s)
- Zhen Yang
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Teng Wang
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Liang-Hao Hu
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
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17
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Schneider A, Hirth M. Pain Management in Chronic Pancreatitis: Summary of Clinical Practice, Current Challenges and Potential Contribution of the M-ANNHEIM Classification. Drugs 2021; 81:533-546. [PMID: 33587287 DOI: 10.1007/s40265-021-01472-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/23/2021] [Indexed: 01/06/2023]
Abstract
Abdominal pain, diarrhea with weight loss, and endocrine insufficiency represent the dominant symptoms of chronic pancreatitis (CP). High intensity of pain and constant pain have been shown to reduce quality of life in CP and may result in disability and increased health resource utilization. Various basic challenges and unanswered questions still exist regarding the treatment of pain in CP. Recently, limited evidence has been gained that early surgery for painful disease might be associated with better treatment results. Thus, timing of pancreatic surgery in painful disease represents a major issue that needs to be clarified in future studies. In this context, surveillance of patients is necessary in clinical practice. It appears that a generally accepted classification of the disease represents a major requirement for inter-institutional comparison of data with future progress in clinical research. Among recently proposed classification systems, the M-ANNHEIM classification system of CP with its recently presented M-ANNHEIM Surgery Score might be a useful tool to picture the course of the disease and to monitor treatment results. Future research is required to clarify the possible role of this system in the management of pain in CP. In the present article, we provide an overview of current status, challenges, and unanswered questions in the treatment of pain in CP, and we demonstrate the potential benefits of the M-ANNHEIM classification system in the management of painful CP.
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Affiliation(s)
- Alexander Schneider
- Department of Gastroenterology and Hepatology, Medical Center Bad Hersfeld-Rotenburg, Bad Hersfeld, Germany. .,Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
| | - Michael Hirth
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
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18
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Abstract
There is tremendous interpatient variability in the response to analgesic therapy
(even for efficacious treatments), which can be the source of great frustration
in clinical practice. This has led to calls for “precision
medicine” or personalized pain therapeutics (ie, empirically based
algorithms that determine the optimal treatments, or treatment combinations, for
individual patients) that would presumably improve both the clinical care of
patients with pain and the success rates for putative analgesic drugs in phase 2
and 3 clinical trials. However, before implementing this approach, the
characteristics of individual patients or subgroups of patients that increase or
decrease the response to a specific treatment need to be identified. The
challenge is to identify the measurable phenotypic characteristics of patients
that are most predictive of individual variation in analgesic treatment
outcomes, and the measurement tools that are best suited to evaluate these
characteristics. In this article, we present evidence on the most promising of
these phenotypic characteristics for use in future research, including
psychosocial factors, symptom characteristics, sleep patterns, responses to
noxious stimulation, endogenous pain-modulatory processes, and response to
pharmacologic challenge. We provide evidence-based recommendations for core
phenotyping domains and recommend measures of each domain.
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19
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Ramaswamy S, Wodehouse T. Conditioned pain modulation-A comprehensive review. Neurophysiol Clin 2020; 51:197-208. [PMID: 33334645 DOI: 10.1016/j.neucli.2020.11.002] [Citation(s) in RCA: 95] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 11/25/2020] [Accepted: 11/28/2020] [Indexed: 01/05/2023] Open
Abstract
Conditioned pain modulation (CPM) is a centrally processed measure of the net effect of the descending pain pathway. This comprises both the facilitatory as well as the inhibitory effect. In the past, CPM or similar effects have been previously described using different terminologies such as diffuse noxious inhibitory control (DNIC), heterotopic noxious conditioning stimulation (HNCS) or endogenous analgesia (EA). A variety of patient-related factors such as age, gender, hormones, race, genetic and psychological factors have been thought to influence the CPM paradigms. CPM paradigms have also been associated with a wide range of methodological variables including the mode of application of the 'test' as well as the 'conditioning' stimuli. Despite all these variabilities, CPM seems to reliably lend itself to the pain modulation profile concept and could in future become one of the phenotypic biomarkers for pain and also a guide for mechanism-based treatment in chronic pain. Future research should focus on establishing consistent methodologies for measuring CPM and thereby enhancing the robustness of this emerging biomarker for pain.
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Affiliation(s)
- Shankar Ramaswamy
- 1St Bartholomew's Hospital, Bart's Health NHS Trust, London, EC1A 4AS, UK.
| | - Theresa Wodehouse
- 1St Bartholomew's Hospital, Bart's Health NHS Trust, London, EC1A 4AS, UK
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20
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Patient and Disease Characteristics Associate With Sensory Testing Results in Chronic Pancreatitis. Clin J Pain 2020; 35:786-793. [PMID: 31268890 PMCID: PMC6693925 DOI: 10.1097/ajp.0000000000000740] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Abdominal pain is the most common symptom in chronic pancreatitis (CP) and has an extensive impact on patients' lives. Quantitative sensory testing (QST) provides information on sensitivity to pain and mechanisms that can help quantify pain and guide treatment. The aims of this study were (1) to explore sensitivity to pain in patients with CP using QST and (2) to associate patient and disease characteristics with QST results. METHODS Ninety-one patients with painful CP and 28 healthy control participants completed a QST paradigm using static tests (muscle pressure stimulation and electrical skin stimulations) to unravel segmental and widespread hyperalgesia as a consequence of visceral pain. A dynamic conditioned pain modulation (CPM) paradigm was used as a proxy of pain modulation from the brainstem to inhibit incoming nociceptive barrage, and questionnaires were used to gather information on pain experience and quality of life. RESULTS Patients had impaired CPM compared with controls (18.0±29.3% vs. 30.9±29.3%, P=0.04) and were hypersensitive to pressure stimulation, specifically in the pancreatic (Th10) dermatome (P<0.001). The capacity of CPM was associated with clinical pain intensity (P=0.01) and (in the univariate analysis only) the use of opioids was associated with hyperalgesia to pressure stimulation (P<0.05). CONCLUSIONS Sensitivity to pain in CP patients can be characterized by a simple bedside QST. Severe clinical pain in CP was associated with reduced CPM function and should be targeted in management.
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21
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Yoneda S, Kasai E, Matsuo M, Tamano R, Sakurai Y, Asaki T, Fujita M. Duloxetine ameliorates the impairment of diffuse noxious inhibitory control in rat models of peripheral neuropathic pain and knee osteoarthritis pain. Neurosci Lett 2020; 729:134990. [PMID: 32315711 DOI: 10.1016/j.neulet.2020.134990] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 04/09/2020] [Accepted: 04/14/2020] [Indexed: 12/14/2022]
Abstract
Diffuse noxious inhibitory control (DNIC) is a phenomenon to reflect descending pain modulation in animals. Conditioned pain modulation (CPM) is the human counterpart of DNIC and is reduced in patients with several chronic pain conditions. Duloxetine is a serotonin and noradrenaline reuptake inhibitor that ameliorates CPM impairment in patients with diabetic neuropathy. Although some studies have reported the effects of different pharmacological agents on CPM, few studies have compared the effects of some analgesics in both humans and rodents. Therefore, we established a stable evaluation method for DNIC in rats and determined whether duloxetine and other specific analgesics affect DNIC impairment in rat models of peripheral neuropathic pain and osteoarthritis pain, two types of chronic pain. As a conditioning stimulus, capsaicin was injected into the forepaw of rats. The paw withdrawal threshold (PWT) in response to mechanical pressure was measured for the hindpaw. Peripheral neuropathic pain and osteoarthritis pain models were developed by partial sciatic nerve ligation (PSNL) and the intra-articular injection of 2 mg monoiodoacetate (MIA), respectively. Capsaicin (30-100 μg/site) increased the PWT, in a dose-dependent manner, in naive rats. The threshold significantly increased at 30 μg and reached its maximal level at 100 μg. The change in PWT following capsaicin injection was significantly reduced in PSNL-treated rats, but the threshold was increased by the subcutaneous administration of duloxetine (10 mg/kg). The oral administrations of pregabalin (10 mg/kg) and celecoxib (3 mg/kg) did not affect the PWT in PSNL-treated rats. Similarly, MIA-injected rats also showed a reduced change in PWT following capsaicin injection. Duloxetine, but not pregabalin and celecoxib, significantly increased the PWT in MIA-injected rats. These results suggested that duloxetine can directly ameliorate DNIC impairment in rat models of chronic pain. Duloxetine may be useful for modulating chronic pain by restoring function to the endogenous, descending, inhibitory pathway.
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Affiliation(s)
- Sosuke Yoneda
- Neuroscience, Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., 1-1 3chome, Futaba-cho, Toyonaka, Osaka, 561-0825, Japan
| | - Erika Kasai
- Neuroscience, Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., 1-1 3chome, Futaba-cho, Toyonaka, Osaka, 561-0825, Japan
| | - Midori Matsuo
- Neuroscience, Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., 1-1 3chome, Futaba-cho, Toyonaka, Osaka, 561-0825, Japan
| | - Ryuta Tamano
- Neuroscience, Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., 1-1 3chome, Futaba-cho, Toyonaka, Osaka, 561-0825, Japan
| | - Yusuke Sakurai
- Neuroscience, Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., 1-1 3chome, Futaba-cho, Toyonaka, Osaka, 561-0825, Japan
| | - Toshiyuki Asaki
- Neuroscience, Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., 1-1 3chome, Futaba-cho, Toyonaka, Osaka, 561-0825, Japan
| | - Masahide Fujita
- Neuroscience, Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., 1-1 3chome, Futaba-cho, Toyonaka, Osaka, 561-0825, Japan.
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22
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Dickenson AH, Patel R. Translational issues in precision medicine in neuropathic pain. CANADIAN JOURNAL OF PAIN-REVUE CANADIENNE DE LA DOULEUR 2020; 4:30-38. [PMID: 32258972 PMCID: PMC7077367 DOI: 10.1080/24740527.2020.1720502] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 01/14/2020] [Accepted: 01/21/2020] [Indexed: 02/08/2023]
Abstract
Neuropathic pain remains poorly treated, with most new drugs falling through the translational gap. The traditional model of bench-to-bedside research has relied on identifying new mechanisms/targets in animal models and then developing clinical applications. Several have advocated bridging the translational gap by beginning with clinical observations and back-translating to animal models for further investigation of mechanisms. There is good evidence that phenotyping of patients through quantitative sensory testing can lead to improved treatment selection and hence improved patient outcomes. This practice has been widely adopted in clinical investigations, but its application in preclinical research is not mainstream. In this review, we retrospectively examine our historical rodent data sets with the aim of reconsidering drug effects on sensory neuronal endpoints, their alignment with clinical observations, and how these might guide future clinical studies.
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Affiliation(s)
- Anthony H Dickenson
- Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK
| | - Ryan Patel
- Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK
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23
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A clinically feasible method for the assessment and characterization of pain in patients with chronic pancreatitis. Pancreatology 2020; 20:25-34. [PMID: 31787527 DOI: 10.1016/j.pan.2019.11.007] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 11/14/2019] [Accepted: 11/18/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Pain is the primary symptom of chronic pancreatitis (CP), but methods for sensory testing and pain characterization have not previously been validated for clinical use. We present a clinically feasible method for the assessment and characterization of pain mechanisms in patients with CP based on quantitative sensory testing (QST). METHODS This was a cross-sectional, multicenter study of 122 control subjects without pancreatic disease and another 60 patients with painful CP. All subjects underwent standardized QST assessments including a cold pressor test, a conditioned pain modulation paradigm, repetitive pin-prick stimuli (temporal summation) and pressure stimulation of the upper abdominal (pancreatic) and control dermatomes. The effects of age and gender on QST assessment parameters were investigated and normative reference values based on quartile regression were derived and implemented in algorithms to categorize patients according to their patterns of central pain processing (normal vs. segmental sensitization vs. widespread sensitization). RESULTS Absolute pressure thresholds were subject to clinically relevant gender effects (all p < 0.001), while the remainder of QST parameters were unaffected by age and gender. The algorithm with the best discriminatory capacity showed good separation between patients and controls (p < 0.001); 50% of patients had normal central pain processing, 23% had evidence of segmental sensitization and 27% had evidence of widespread sensitization. CONCLUSION We show normative reference values for a clinically feasible method for assessment and characterization of pain mechanisms in patients with CP. Application of this method streamlines the evaluation of pancreatic pain and may be used to inform treatment. CLINICALTRIALS. GOV ID NCT03434392.
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Ozasa K, Nishihara C, Watanabe K, Young A, Khan J, Sim C, Yamamoto A, Imamura Y, Noma N. Somatosensory profile of a patient with mixed connective tissue disease and Sjögren syndrome. J Am Dent Assoc 2019; 151:145-151. [PMID: 31879015 DOI: 10.1016/j.adaj.2019.09.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 08/06/2019] [Accepted: 09/07/2019] [Indexed: 11/30/2022]
Abstract
BACKGROUND AND OVERVIEW The authors report the case of a patient with mixed connective tissue disease (MCTD) and Sjögren syndrome, showing signs and symptoms of bilateral trigeminal neuropathy and aseptic meningitis. The patient was assessed by means of quantitative sensory testing (QST) according to the German Research Network on Neuropathic Pain standards, in both the gingiva and forearm, and the results were compared with those of healthy control participants. CASE DESCRIPTION A 27-year-old woman, who had received a diagnosis of MCTD and Sjögren syndrome from a rheumatologist, sought treatment at an orofacial pain clinic for bilateral electriclike pain in the maxillary anterior gingiva, eyelids, and cheeks. QST indicated allodynia and hyperalgesia in response to mechanical and thermal stimuli in both her gingiva and forearm, and cold hyperalgesia in her forearm only. She had been prescribed an oral corticosteroid (prednisone, 7 milligrams per day) by the rheumatologist, and was given lidocaine gel and systemic pregabalin (400 mg/d) at the clinic. CONCLUSIONS AND PRACTICAL IMPLICATIONS The cause of trigeminal neuropathy in MCTD and Sjögren syndrome (SS) is unknown. The QST data in this case showed that the somatosensory disturbance severity was higher in the gingiva than in the forearm, suggesting that the trigeminal nerve may be more susceptible than other parts of the nervous system in patients with MCTD. If reproducible in future studies, the finding of greater hypersensitivity in the gingiva than in the forearm may provide an opportunity for dentists to play a role in the detection, diagnosis, or both of MCTD and SS. Dentists must be sufficiently familiar with MCTD and SS to include them in their differential diagnoses and should consider performing simple neurosensory testing such as via intraoral cotton swab or pinprick test.
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Rising Prevalence of Opioid Use Disorder and Predictors for Opioid Use Disorder Among Hospitalized Patients With Chronic Pancreatitis. Pancreas 2019; 48:1386-1392. [PMID: 31688606 DOI: 10.1097/mpa.0000000000001430] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES We aimed to evaluate the prevalence, impact, and predictors of opioid use disorder (OUD) in hospitalized chronic pancreatitis (CP) patients. METHODS A retrospective cohort study was performed using the National Inpatient Sample database from 2005 to 2014. Patients with a primary diagnosis of CP and OUD were included. The primary outcome was evaluating the prevalence and trend of OUD in patients hospitalized with CP. Secondary outcomes were to (1) assess the impact of OUD on health care resource utilization and (2) identify predictors of OUD in hospitalized CP patients. RESULTS A total of 176,857 CP patients were included, and OUD was present in 3.8% of patients. The prevalence of OUD in CP doubled between 2005 and 2014. Patients with CP who had OUD were found to have higher mean length of stay (adjusted mean difference, 1.2 days; P < 0.001) and hospitalization costs (adjusted mean difference, US $1936; P < 0.001). Independent predictors of OUD in CP patients were obesity, presence of depression, and increased severity of illness. CONCLUSIONS Opioid use disorder-related diagnoses are increasing among CP patients and are associated with increased health care resource utilization. Our study identifies patients at high-risk for OUD whose pain should be carefully managed.
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Assessment of conditioned pain modulation in healthy participants and patients with chronic pain: manifestations and implications for pain progression. Curr Opin Support Palliat Care 2019; 13:99-106. [DOI: 10.1097/spc.0000000000000419] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Lockwood SM, Dickenson AH. A combination pharmacotherapy of tapentadol and pregabalin to tackle centrally driven osteoarthritis pain. Eur J Pain 2019; 23:1185-1195. [PMID: 30821870 PMCID: PMC6618140 DOI: 10.1002/ejp.1386] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 01/29/2019] [Accepted: 02/24/2019] [Indexed: 11/10/2022]
Abstract
BACKGROUND Many Osteoarthritis (OA) patients report with clinical features to their pain that cannot be explained by purely peripheral mechanisms. Yet, the analgesic agents available that tackle centrally driven chronic pain often provide only partial pain relief, or have dose-limiting side effects. We explored a combination therapy of the centrally acting analgesic agents tapentadol and pregabalin, to investigate if they could be used in combination to provide superior analgesia. METHODS Using electrophysiological single-unit recordings taken from spinal wide dynamic range neurons, Diffuse Noxious Inhibitory Controls (DNIC) were assessed as a marker of potential changes in descending controls in a monoiodoacetate (MIA) model of OA. We investigated if a subcutaneous injection of tapentadol or pregabalin, both alone and in combination, inhibited neuronal responses and restored the expression of DNIC, quantified as a reduction in neuronal firing in the presence of a conditioning noxious stimulus. RESULTS Tapentadol restored DNIC-induced neuronal inhibition in MIA animals, while pregabalin inhibited pre-conditioned mechanically evoked neuronal responses but did not restore DNIC. Given in combination, tapentadol and pregabalin restored DNIC expression and also inhibited spinal neuronal responses. CONCLUSIONS We propose that there is both central sensitization and an imbalance in inhibitory and facilitatory descending controls in MIA animals. The combination therapy of tapentadol and pregabalin restored descending noradrenergic inhibitory tone and also inhibited nociceptive transmission at the level of the spinal cord. SIGNIFICANCE This study shows that pregabalin and tapentadol target different mechanisms of centrally driven chronic pain associated with osteoarthritis, and that when administered together can restore descending inhibitory tone whilst also tackling spinal neuronal hyperexcitability and may therefore provide superior analgesia.
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Affiliation(s)
| | - Anthony H Dickenson
- Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK
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Kuhlmann L, Olesen SS, Olesen AE, Arendt-Nielsen L, Drewes AM. Mechanism-based pain management in chronic pancreatitis - is it time for a paradigm shift? Expert Rev Clin Pharmacol 2019; 12:249-258. [PMID: 30664364 DOI: 10.1080/17512433.2019.1571409] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Pain is the most common symptom in chronic pancreatitis and treatment remains a challenge. Management of visceral pain, in general, is only sparsely documented, and treatment in the clinic is typically based on empirical knowledge from somatic pain conditions. This may be problematic, as many aspects of the neurobiology differ significantly from somatic pain, and organs such as the gut and liver play a major role in tolerability to analgesics. On the other hand, clinical awareness and new methods for quantitative assessment of pain mechanisms, will likely increase our understanding of the visceral pain system and guide more individualized pain management. Areas covered: This review includes an overview of known pain mechanisms in chronic pancreatitis and how to characterize them using quantitative sensory testing. The aim is to provide a mechanism-oriented approach to analgesic treatment, including treatment of psychological factors affecting pain perception and consideration of side effects in the management plan. Expert opinion: A mechanism-based examination and profiling of pain in chronic pancreatitis will enable investigators to provide a well-substantiated approach to effective management. This mechanism-based, individualized regime will pave the road to better pain relief and spare the patient from unnecessary trial-and-error approaches and unwanted side effects.
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Affiliation(s)
- Louise Kuhlmann
- a Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology , Aalborg University Hospital , Aalborg , Denmark.,b Department of Internal Medicine , North Denmark Regional Hospital , Hjørring , Denmark.,c Department of Clinical Medicine , Aalborg University , Aalborg , Denmark
| | - Søren S Olesen
- a Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology , Aalborg University Hospital , Aalborg , Denmark.,c Department of Clinical Medicine , Aalborg University , Aalborg , Denmark
| | - Anne E Olesen
- a Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology , Aalborg University Hospital , Aalborg , Denmark.,c Department of Clinical Medicine , Aalborg University , Aalborg , Denmark
| | - Lars Arendt-Nielsen
- d Center for Sensory-Motor Interaction, School of Medicine , Aalborg University , Aalborg , Denmark
| | - Asbjørn M Drewes
- a Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology , Aalborg University Hospital , Aalborg , Denmark.,c Department of Clinical Medicine , Aalborg University , Aalborg , Denmark
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van Aken M, Oosterman J, van Rijn T, Woudsma K, Ferdek M, Ruigt G, Kozicz T, Braat D, Peeters A, Nap A. Experimental pain tolerance is decreased and independent of clinical pain intensity in patients with endometriosis. Fertil Steril 2018; 110:1118-1128. [DOI: 10.1016/j.fertnstert.2018.06.040] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 06/26/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023]
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Maev IV, Bideeva ТВ, Kucheryavyy YA, Andreev DN, Bueverov AO. Pharmacotherapy of chronic pancreatitis in terms of current clinical recommendations. TERAPEVT ARKH 2018; 90:81-85. [PMID: 30701942 DOI: 10.26442/terarkh201890881-85] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The article reflects the main positions of the latest Russian and pan-European clinical recommendations on the diagnosis and treatment of chronic pancreatitis (CP), devoted to the pharmacotherapy of this disease. The main objectives of pharmacotherapy for CP are to reduce or arrest pain abdominal syndrome and prevent or compensate for functional pancreatic insufficiency.
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Affiliation(s)
- I V Maev
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
| | - Т В Bideeva
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
| | - Yu A Kucheryavyy
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
| | - D N Andreev
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
| | - A O Bueverov
- I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia
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Wodehouse T, Poply K, Ramaswamy S, Snidvongs S, Bourke J, Tahir H, Ullrich K, Mehta V. A pilot study investigating whether quantitative sensory testing alters after treatment in patients with fibromyalgia. Br J Pain 2018; 12:250-256. [PMID: 30349699 DOI: 10.1177/2049463718776336] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background Fibromyalgia is a chronic musculoskeletal pain condition that is often associated with sleep disturbances and fatigue. The pathophysiology of fibromyalgia is not understood, but indirect evidence suggests a central dysfunction of the nociceptive modulating system. The aim of this study was to evaluate whether quantitative sensory testing detects a change in pain thresholds in fibromyalgia patient receiving pregabalin treatment. Methods A total of 25 patients were recruited for the study and received routine pregabalin, but only 14 patients completed the treatment. Assessment of pressure pain thresholds and changes in conditioned pain modulation using ischaemic pain as a conditioning stimulus were measured at baseline and every 4 weeks for 12 weeks. Fibromyalgia impact questionnaire, PainDETECT and SF-12 were also completed. Results Patients with fibromyalgia demonstrated a less-efficient conditioned pain modulation at baseline. An efficient conditioned pain modulation was observed at 1 month and this was maintained until the final visit. Pressure pain thresholds (PPTs) showed a significant improvement from baseline. Patients also reported a similar magnitude of improvements in PainDETECT, fibromyalgia impact questionnaire (FIQ) and its impact on daily life and change in outcome for SF-12. Conclusion This pilot study reports an increase in PPTs and improved conditioned pain modulation response after commencing pregabalin, which was maintained at 12 weeks, and this was supported by positive pain scores. Pregabalin is a licenced treatment for fibromyalgia in Europe, and its response to central sensitisation, particularly 'dynamic responses', has not been reported. We conclude that pregabalin has the potential to reduce peripheral and central sensitisation in patients with fibromyalgia, as measured using quantitative sensory testing.
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Affiliation(s)
- Theresa Wodehouse
- Pain and Anaesthesia Research Centre, Barts Health NHS Trust, London, UK
| | - Kavita Poply
- Pain and Anaesthesia Research Centre, Barts Health NHS Trust, London, UK
| | - Shankar Ramaswamy
- Pain and Anaesthesia Research Centre, Barts Health NHS Trust, London, UK
| | - Saowarat Snidvongs
- Pain and Anaesthesia Research Centre, Barts Health NHS Trust, London, UK
| | - Julius Bourke
- Centre for Psychiatry, Barts Health NHS Trust, London, UK
| | - Hasan Tahir
- Rheumatology, Whipps Cross University Hospital, Barts Health NHS Trust, London, UK
| | - Kristin Ullrich
- Anaesthetic and Pain Management Department, Barts Health NHS Trust, London, UK
| | - Vivek Mehta
- Pain and Anaesthesia Research Centre, Barts Health NHS Trust, London, UK
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Arendt‐Nielsen L, Morlion B, Perrot S, Dahan A, Dickenson A, Kress H, Wells C, Bouhassira D, Drewes AM. Assessment and manifestation of central sensitisation across different chronic pain conditions. Eur J Pain 2018; 22:216-241. [DOI: 10.1002/ejp.1140] [Citation(s) in RCA: 435] [Impact Index Per Article: 62.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
AbstractDifferent neuroplastic processes can occur along the nociceptive pathways and may be important in the transition from acute to chronic pain and for diagnosis and development of optimal management strategies. The neuroplastic processes may result in gain (sensitisation) or loss (desensitisation) of function in relation to the incoming nociceptive signals. Such processes play important roles in chronic pain, and although the clinical manifestations differ across condition processes, they share some common mechanistic features. The fundamental understanding and quantitative assessment of particularly some of the central sensitisation mechanisms can be translated from preclinical studies into the clinic. The clinical perspectives are implementation of such novel information into diagnostics, mechanistic phenotyping, prevention, personalised treatment, and drug development. The aims of this paper are to introduce and discuss (1) some common fundamental central pain mechanisms, (2) how they may translate into the clinical signs and symptoms across different chronic pain conditions, (3) how to evaluate gain and loss of function using quantitative pain assessment tools, and (4) the implications for optimising prevention and management of pain. The chronic pain conditions selected for the paper are neuropathic pain in general, musculoskeletal pain (chronic low back pain and osteoarthritic pain in particular), and visceral pain (irritable bowel syndrome in particular). The translational mechanisms addressed are local and widespread sensitisation, central summation, and descending pain modulation.SignificanceCentral sensitisation is an important manifestation involved in many different chronic pain conditions. Central sensitisation can be different to assess and evaluate as the manifestations vary from pain condition to pain condition. Understanding central sensitisation may promote better profiling and diagnosis of pain patients and development of new regimes for mechanism based therapy. Some of the mechanisms underlying central sensitisation can be translated from animals to humans providing new options in development of therapies and profiling drugs under development.
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Affiliation(s)
| | - B. Morlion
- The Leuven Centre for Algology University Hospitals Leuven University of Leuven Belgium
| | - S. Perrot
- INSERM U987 Pain Center Cochin Hospital Paris Descartes University Paris France
| | - A. Dahan
- Department of Anesthesiology Leiden University Medical Center Leiden The Netherlands
| | - A. Dickenson
- Neuroscience Physiology & Pharmacology University College London UK
| | - H.G. Kress
- Department of Special Anaesthesia and Pain Therapy Medizinische Universität/AKH Wien Vienna Austria
| | | | - D. Bouhassira
- INSERM U987 Centre d'Evaluation et de Traitement de la Douleur Hôpital Ambroise Paré Boulogne Billancourt France
| | - A. Mohr Drewes
- Mech‐Sense Department of Gastroenterology and Hepatology Clinical Institute Aalborg University Hospital Aalborg Denmark
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Abstract
PURPOSE OF REVIEW Summarize key clinical advances in chronic pancreatitis reported in 2016. RECENT FINDINGS Early diagnosis of chronic pancreatitis remains elusive. Recent studies suggest that endoscopic ultrasound may be less accurate than previously thought and new MRI techniques may be helpful. Genetic predisposition may independently affect the clinical course of chronic pancreatitis and the risk for pancreatic cancer. Cigarette smoking may have a greater negative impact on chronic pancreatitis than previously thought and moderate alcohol consumption may be protective. A multidisciplinary approach is necessary for the treatment of type 3 diabetes and nutritional deficiencies in chronic pancreatitis. Although endoscopic therapy remains a reasonable first-line option in treating chronic pancreatitis and its complications, early surgical intervention may be indicated for pain in select patients. SUMMARY Newer endoscopic ultrasound and MRI techniques are being evaluated to help with the early diagnosis of chronic pancreatitis. Both genetic predisposition and cigarette smoking are increasingly recognized as having a major impact in the course of the disease and the risk for pancreatic cancer. Endoscopic therapy is well tolerated and effective for the treatment of chronic pancreatitis and its complications although an early surgical approach for pain may be associated with improved clinical outcomes.
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Drewes AM, Bouwense SAW, Campbell CM, Ceyhan GO, Delhaye M, Demir IE, Garg PK, van Goor H, Halloran C, Isaji S, Neoptolemos JP, Olesen SS, Palermo T, Pasricha PJ, Sheel A, Shimosegawa T, Szigethy E, Whitcomb DC, Yadav D. Guidelines for the understanding and management of pain in chronic pancreatitis. Pancreatology 2017; 17:720-731. [PMID: 28734722 DOI: 10.1016/j.pan.2017.07.006] [Citation(s) in RCA: 187] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Revised: 06/26/2017] [Accepted: 07/11/2017] [Indexed: 12/11/2022]
Abstract
Abdominal pain is the foremost complication of chronic pancreatitis (CP). Pain can be related to recurrent or chronic inflammation, local complications or neurogenic mechanisms with corresponding changes in the nervous systems. Both pain intensity and the frequency of pain attacks have been shown to reduce quality of life in patients with CP. Assessment of pain follows the guidelines for other types of chronic pain, where the multidimensional nature of symptom presentation is taken into consideration. Quantitative sensory testing may be used to characterize pain, but is currently used in a research setting in advanced laboratories. For pain relief, current guidelines recommend a simple stepwise escalation of analgesic drugs with increasing potency until pain relief is obtained. Abstinence from alcohol and smoking should be strongly advised. Pancreatic enzyme therapy and antioxidants may be helpful as initial treatment. Endoscopic treatment can be used in patients with evidence of ductal obstruction and may be combined with extracorporeal shock wave lithothripsy. The best candidates are those with distal obstruction of the main pancreatic duct and in early stage of disease. Behavioral interventions should be part of the multidisciplinary approach to chronic pain management particularly when psychological impact is experienced. Surgery should be considered early and after a maximum of five endoscopic interventions. The type of surgery depends on morphological changes of the pancreas. Long-term effects are variable, but high success rates have been reported in open studies and when compared with endoscopic treatment. Finally, neurolytical interventions and neuromodulation can be considered in difficult patients.
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Affiliation(s)
- Asbjørn M Drewes
- Centre for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark.
| | - Stefan A W Bouwense
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Claudia M Campbell
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Güralp O Ceyhan
- Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - Myriam Delhaye
- Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium
| | - Ihsan Ekin Demir
- Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - Pramod K Garg
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Harry van Goor
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | | | - Shuiji Isaji
- Department of Surgery, Mie University Graduate School of Medicine, Japan
| | - John P Neoptolemos
- Institute of Translational Medicine, University of Liverpool, United Kingdom
| | - Søren S Olesen
- Centre for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark
| | - Tonya Palermo
- Seattle Children's Hospital Research Institute, Washington School of Medicine, USA
| | - Pankaj Jay Pasricha
- Center for Neurogastroenterology, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Andrea Sheel
- Institute of Translational Medicine, University of Liverpool, United Kingdom
| | - Tooru Shimosegawa
- Department of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Eva Szigethy
- Visceral Inflammation and Pain Center, Division of Gastroenterology, University of Pittsburgh and UPMC, Pittsburgh, PA, USA
| | - David C Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh and UPMC, Pittsburgh, PA, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh and UPMC, Pittsburgh, PA, USA
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Fan CJ, Hirose K, Walsh CM, Quartuccio M, Desai NM, Singh VK, Kalyani RR, Warren DS, Sun Z, Hanna MN, Makary MA. Laparoscopic Total Pancreatectomy With Islet Autotransplantation and Intraoperative Islet Separation as a Treatment for Patients With Chronic Pancreatitis. JAMA Surg 2017; 152:550-556. [PMID: 28241234 DOI: 10.1001/jamasurg.2016.5707] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Importance Pain management of patients with chronic pancreatitis (CP) can be challenging. Laparoscopy has been associated with markedly reduced postoperative pain but has not been widely applied to total pancreatectomy with islet autotransplantation (TPIAT). Objective To examine the feasibility of using laparoscopic TPIAT (L-TPIAT) in the treatment of CP. Design, Setting, and Participants Thirty-two patients with CP presented for TPIAT at a tertiary hospital from January 1, 2013, through December 31, 2015. Of the 22 patients who underwent L-TPIAT, 2 patients converted to an open procedure because of difficult anatomy and prior surgery. Pain and glycemic outcomes were recorded at follow-up visits every 3 to 6 months postoperatively. Main Outcomes and Measures Operative outcomes included operative time, islet isolation time, warm ischemia time, islet equivalent (IE) counts, estimated blood loss, fluid resuscitation, and blood transfusions. Postoperative outcomes included length of stay, all-cause 30-day readmission rate, postoperative complications, mortality rate, subjective pain measurements, opioid use, random C-peptide levels, insulin requirements, and glycated hemoglobin level. Results Of the 32 patients who presented for TPIAT, 20 underwent L-TPIAT (8 men and 12 women; mean [SD] age, 39 [13] years; age range, 21-58 years). Indication for surgery was CP attributable to genetic mutation (n = 9), idiopathic pancreatitis (n = 6), idiopathic pancreatitis with pancreas divisum (n = 3), and alcohol abuse (n = 2). Mean (SD) operative time was 493 (78) minutes, islet isolation time was 185 (37) minutes, and warm ischemia time was 51 (62) minutes. The mean (SD) IE count was 1325 (1093) IE/kg. The mean (SD) length of stay was 11 (5) days, and the all-cause 30-day readmission rate was 35% (7 of 20 patients). None of the patients experienced postoperative surgical site infection, hernia, or small-bowel obstruction, and none died. Eighteen patients (90%) had a decrease or complete resolution of pain, and 12 patients (60%) no longer required opioid therapy at a median follow-up period of 6 months. Postoperative random insulin C-peptide levels were detectable in 19 patients (95%) at a median follow-up of 10.4 months. At a median follow-up of 12.5 months, 5 patients (25%) were insulin independent, whereas 9 patients (45%) required 1 to 10 U/d, 5 patients (25%) required 11 to 20 U/d, and 1 patient (5%) required greater than 20 U/d of basal insulin. The mean (SD) glycated hemoglobin level was 7.4% (0.5%). Conclusions and Relevance This study represents the first series of L-TPIAT, demonstrating its safety and feasibility. Our approach enables patients to experience shorter operative times and the benefits of laparoscopy, including reduced length of stay and quicker opioid independence.
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Affiliation(s)
- Caleb J Fan
- School of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Kenzo Hirose
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland3Department of Surgery, University of California, San Francisco
| | - Christi M Walsh
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland
| | | | - Niraj M Desai
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland
| | - Vikesh K Singh
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Rita R Kalyani
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Daniel S Warren
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland
| | - Zhaoli Sun
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland
| | - Marie N Hanna
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Martin A Makary
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland
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Lew D, Afghani E, Pandol S. Chronic Pancreatitis: Current Status and Challenges for Prevention and Treatment. Dig Dis Sci 2017; 62:1702-1712. [PMID: 28501969 PMCID: PMC5507364 DOI: 10.1007/s10620-017-4602-2] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Accepted: 05/02/2017] [Indexed: 12/21/2022]
Abstract
This paper reviews the current status of our understanding of the epidemiology, diagnosis, and management of the continuum of pancreatic diseases from acute and recurrent acute pancreatitis to chronic pancreatitis and the diseases that are often linked with pancreatitis including diabetes mellitus and pancreatic cancer. In addition to reviewing the current state of the field, we identify gaps in knowledge that are necessary to address to improve patient outcomes in these conditions.
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Affiliation(s)
- Daniel Lew
- Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA, 90048, USA
| | - Elham Afghani
- Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA, 90048, USA
| | - Stephen Pandol
- Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA, 90048, USA.
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Smith SM, Dworkin RH, Turk DC, Baron R, Polydefkis M, Tracey I, Borsook D, Edwards RR, Harris RE, Wager TD, Arendt-Nielsen L, Burke LB, Carr DB, Chappell A, Farrar JT, Freeman R, Gilron I, Goli V, Haeussler J, Jensen T, Katz NP, Kent J, Kopecky EA, Lee DA, Maixner W, Markman JD, McArthur JC, McDermott MP, Parvathenani L, Raja SN, Rappaport BA, Rice ASC, Rowbotham MC, Tobias JK, Wasan AD, Witter J. The Potential Role of Sensory Testing, Skin Biopsy, and Functional Brain Imaging as Biomarkers in Chronic Pain Clinical Trials: IMMPACT Considerations. THE JOURNAL OF PAIN 2017; 18:757-777. [PMID: 28254585 PMCID: PMC5484729 DOI: 10.1016/j.jpain.2017.02.429] [Citation(s) in RCA: 97] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 01/19/2017] [Accepted: 02/16/2017] [Indexed: 02/08/2023]
Abstract
Valid and reliable biomarkers can play an important role in clinical trials as indicators of biological or pathogenic processes or as a signal of treatment response. Currently, there are no biomarkers for pain qualified by the U.S. Food and Drug Administration or the European Medicines Agency for use in clinical trials. This article summarizes an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials meeting in which 3 potential biomarkers were discussed for use in the development of analgesic treatments: 1) sensory testing, 2) skin punch biopsy, and 3) brain imaging. The empirical evidence supporting the use of these tests is described within the context of the 4 categories of biomarkers: 1) diagnostic, 2) prognostic, 3) predictive, and 4) pharmacodynamic. Although sensory testing, skin punch biopsy, and brain imaging are promising tools for pain in clinical trials, additional evidence is needed to further support and standardize these tests for use as biomarkers in pain clinical trials. PERSPECTIVE The applicability of sensory testing, skin biopsy, and brain imaging as diagnostic, prognostic, predictive, and pharmacodynamic biomarkers for use in analgesic treatment trials is considered. Evidence in support of their use and outlining problems is presented, as well as a call for further standardization and demonstrations of validity and reliability.
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Abstract
The medical management of pain in chronic pancreatitis continues to pose significant challenges for clinicians caring for these patients. There are increasing data, suggesting that pain in chronic pancreatitis is largely due to peripheral and central sensitization that evolves, over time, as a result of nociceptive afferent associated with chronic inflammation and fibrosis of the pancreas. In many instances, patients rapidly progress to requiring opioid analgesics for the adequate treatment of pain despite the unequivocal risks associated with the long-term use of these drugs. Centrally acting drugs, such as gabapentinoids, appear to be effective means of treating pain due to their inhibition of neurotransmitters involved in central sensitization, but side effects limit their use. The present review explores the evidence for various non-pharmacologic and pharmacologic treatments for pain in chronic pancreatitis.
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Juel J, Brock C, Olesen SS, Madzak A, Farmer AD, Aziz Q, Frøkjær JB, Drewes AM. Acute physiological and electrical accentuation of vagal tone has no effect on pain or gastrointestinal motility in chronic pancreatitis. J Pain Res 2017; 10:1347-1355. [PMID: 28615966 PMCID: PMC5459955 DOI: 10.2147/jpr.s133438] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Background The effective management of pain in chronic pancreatitis (CP) remains a therapeutic challenge. Analgesic drugs, such as opioids, and the underlying pathology can impair gut function. The autonomic nervous system influences hormone secretion and gut motility. In healthy volunteers, electrical (using noninvasive transcutaneous vagal nerve stimulation [t-VNS]) and physiological (using deep slow breathing [DSB]) modulation of parasympathetic tone results in pain attenuation and enhanced gut motility. Thus, the aims were to investigate whether t-VNS and DSB could enhance the parasympathetic tone, decrease pain sensitivity and improve gut motility in CP. Patients and methods A total of 20 patients (12 males, mean age=61 years, range: 50–78 years) with CP were randomized to short-term (60 minutes) t-VNS and DSB, or their placebo equivalent, in a crossover design. Cardiometrically derived parameters of autonomic tone, quantitative sensory testing of bone and muscle pain pressure, conditioned pain modulation (CPM) and assessments of gastroduodenal motility with ultrasound were performed. Results In comparison to sham, t-VNS and DSB increased cardiac vagal tone (CVT) (P<0.001). However, no changes in pain pressure thresholds for bone (P=0.95) or muscle (P=0.45) were seen. There was diminished CPM (P=0.04), and no changes in gastroduodenal motility were observed (P=0.3). Conclusion This explorative study demonstrated that t-VNS and DSB increased CVT in patients with CP. However, this short-lasting increase did not affect pain sensitivity to musculoskeletal pain or gastroduodenal motility. The chronic pain in CP patients is complex, and future trials optimizing neuromodulation for pain relief and improved motility are needed.
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Affiliation(s)
- Jacob Juel
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital.,Department of Clinical Medicine, Aalborg University, Aalborg.,Department of Rheumatology, Aarhus University Hospital, Aarhus.,Drug Design and Pharmacology, University of Copenhagen, Copenhagen
| | - Søren S Olesen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital.,Department of Clinical Medicine, Aalborg University, Aalborg
| | - Adnan Madzak
- Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - Adam D Farmer
- Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark.,Department of Gastroenterology, University Hospitals of North Midlands, Stoke-on-Trent.,Centre for Neuroscience and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK
| | - Qasim Aziz
- Centre for Neuroscience and Trauma, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK
| | - Jens B Frøkjær
- Department of Clinical Medicine, Aalborg University, Aalborg.,Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital.,Department of Clinical Medicine, Aalborg University, Aalborg
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Abstract
There is tremendous interpatient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice. This has led to calls for "precision medicine" or personalized pain therapeutics (ie, empirically based algorithms that determine the optimal treatments, or treatment combinations, for individual patients) that would presumably improve both the clinical care of patients with pain and the success rates for putative analgesic drugs in phase 2 and 3 clinical trials. However, before implementing this approach, the characteristics of individual patients or subgroups of patients that increase or decrease the response to a specific treatment need to be identified. The challenge is to identify the measurable phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics. In this article, we present evidence on the most promising of these phenotypic characteristics for use in future research, including psychosocial factors, symptom characteristics, sleep patterns, responses to noxious stimulation, endogenous pain-modulatory processes, and response to pharmacologic challenge. We provide evidence-based recommendations for core phenotyping domains and recommend measures of each domain.
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Unimpaired endogenous pain inhibition in the early phase of complex regional pain syndrome. Eur J Pain 2017; 21:855-865. [DOI: 10.1002/ejp.988] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/05/2016] [Indexed: 12/26/2022]
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Hyperalgesia and Persistent Pain after Breast Cancer Surgery: A Prospective Randomized Controlled Trial with Perioperative COX-2 Inhibition. PLoS One 2016; 11:e0166601. [PMID: 27935990 PMCID: PMC5147830 DOI: 10.1371/journal.pone.0166601] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Accepted: 10/29/2016] [Indexed: 12/21/2022] Open
Abstract
Background Persistent pain is a challenging clinical problem after breast cancer treatment. After surgery, inflammatory pain and nociceptive input from nerve injury induce central sensitization which may play a role in the genesis of persistent pain. Using quantitative sensory testing, we tested the hypothesis that adding COX-2 inhibition to standard treatment reduces hyperalgesia after breast cancer surgery. A secondary hypothesis was that patients developing persistent pain would exhibit more postoperative hyperalgesia. Methods 138 women scheduled for lumpectomy/mastectomy under general anesthesia with paravertebral block were randomized to COX-2 inhibition (2x40mg parecoxib on day of surgery, thereafter 2x200mg celecoxib/day until day five) or placebo. Preoperatively and 1, 5, 15 days and 1, 3, 6, 12 months postoperatively, we determined electric and pressure pain tolerance thresholds in dermatomes C6/T4/L1 and a 100mm VAS score for pain. We calculated the sum of pain tolerance thresholds and analyzed change in these versus preoperatively using mixed models analysis with factor medication. To assess hyperalgesia in persistent pain patients we performed an additional analysis on patients reporting VAS>30 at 12 months. Results 48 COX-2 inhibition and 46 placebo patients were analyzed in a modified intention to treat analysis. Contrary to our primary hypothesis, change in the sum of tolerance thresholds in the COX-2 inhibition group was not different versus placebo. COX-2 inhibition had an effect on pain on movement at postoperative day 5 (p<0.01). Consistent with our secondary hypothesis, change in sum of pressure pain tolerance thresholds in 11 patients that developed persistent pain was negative versus patients without pain (p<0.01) from day 5 to 1 year postoperatively. Conclusions Perioperative COX-2 inhibition has limited value in preventing sensitization and persistent pain after breast cancer surgery. Central sensitization may play a role in the genesis of persistent postsurgical pain.
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Talukdar R, Lakhtakia S, Nageshwar Reddy D, Rao GV, Pradeep R, Banerjee R, Gupta R, Ramchandani M, Tandan M, Murthy HV. Ameliorating effect of antioxidants and pregabalin combination in pain recurrence after ductal clearance in chronic pancreatitis: Results of a randomized, double blind, placebo-controlled trial. J Gastroenterol Hepatol 2016; 31:1654-62. [PMID: 26945817 DOI: 10.1111/jgh.13332] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Revised: 02/14/2016] [Accepted: 02/20/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM The aim of this study was to evaluate the effect of antioxidant-pregabalin combination on pain recurrence in patients with chronic calcific pancreatitis. METHODS In this randomized, double-blind, placebo-controlled trial, chronic calcific pancreatitis patients with pain recurrence following pancreatic ductal clearance of stones received either antioxidant-pregabalin combination or matching placebo for 2 months followed by open-label antioxidants for the next 4 months in both groups. Compliance, daily pain, and adverse events were recorded weekly and at the end of study by a coordinator blinded to treatment status. Primary outcome was pain improvement (visual analog scale and Izbicki score); secondary outcomes were as follows: complete pain resolution, painful days, and adverse events. Number needed-to-treat was calculated. RESULTS We randomized 42 and 45 patients (mean age 29.3 years) to treatment and placebo arms, respectively. Baseline characteristics, including pain scores, were similar for both groups. No patients received high-potency narcotic. At 2 months, a significant improvement in the treatment arm was observed in percent reduction of visual analog scale (-50 [-80.0; -32.1] vs -29.5 [-64.5; 0]; P = 0.01), Izbicki score (14.5 [0; 21.3] vs 30.0 [11.8; 41.3]; P = 0.001), complete pain resolution (20 [47.6%] vs 12 [26.7%]; P = 0.04), and number of painful days (10.0 [2.0; 16.0] vs 18.0 [7.0; 34.0]; P = 0.01). Needed-to-treat was 4.8. Pain reduction persisted at 6 months in the original treatment group (20.0 [15.0; 28.0] vs 36.0 [20.0; 50.0]; P = 0.006). A total of 33 patients in the treatment arm experienced mild to moderate self-limiting nausea/vomiting and drowsiness, respectively and did not require any change in study protocol. CONCLUSION Antioxidant-pregabalin combination results in significant relief in pain recurrence after ductal clearance in narcotic naïve patients with chronic calcific pancreatitis.
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Affiliation(s)
- Rupjyoti Talukdar
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India. .,Wellcome-DBT Laboratory, Asian Healthcare Foundation, Hyderabad, India.
| | - Sundeep Lakhtakia
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - D Nageshwar Reddy
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - G Venkat Rao
- Surgical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Rebala Pradeep
- Surgical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Rupa Banerjee
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Rajesh Gupta
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Mohan Ramchandani
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Manu Tandan
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
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Nijs J, Leysen L, Adriaenssens N, Aguilar Ferrándiz ME, Devoogdt N, Tassenoy A, Ickmans K, Goubert D, van Wilgen CP, Wijma AJ, Kuppens K, Hoelen W, Hoelen A, Moloney N, Meeus M. Pain following cancer treatment: Guidelines for the clinical classification of predominant neuropathic, nociceptive and central sensitization pain. Acta Oncol 2016; 55:659-63. [PMID: 27142228 DOI: 10.3109/0284186x.2016.1167958] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND In addition to fatigue, pain is the most frequent persistent symptom in cancer survivors. Clear guidelines for both the diagnosis and treatment of pain in cancer survivors are lacking. Classification of pain is important as it may facilitate more specific targeting of treatment. In this paper we present an overview of nociceptive, neuropathic and central sensitization pain following cancer treatment, as well as the rationale, criteria and process for stratifying pain classification. MATERIAL AND METHODS Recently, a clinical method for classifying any pain as either predominant central sensitization pain, neuropathic or nociceptive pain was developed, based on a large body of research evidence and international expert opinion. We, a team of 15 authors from 13 different centers, four countries and two continents have applied this classification algorithm to the cancer survivor population. RESULTS The classification of pain following cancer treatment entails two steps: (1) examining the presence of neuropathic pain; and (2) using an algorithm for differentiating predominant nociceptive and central sensitization pain. Step 1 builds on the established criteria for neuropathic pain diagnosis, while Step 2 applies a recently developed clinical method for classifying any pain as either predominant central sensitization pain, neuropathic or nociceptive pain to the cancer survivor population. CONCLUSION The classification criteria allow identifying central sensitization pain following cancer treatment. The recognition of central sensitization pain in practice is an important development in the integration of pain neuroscience into the clinic, and one that is relevant for people undergoing and following cancer treatment.
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Affiliation(s)
- Jo Nijs
- Pain in Motion International Research Group,
- Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium
- Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Belgium
| | - Laurence Leysen
- Pain in Motion International Research Group,
- Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium
| | - Nele Adriaenssens
- Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium
- Department of Oncology, University Hospital Brussels, Belgium
| | | | - Nele Devoogdt
- Department of Physical Medicine and Rehabilitation, University Hospitals Leuven, Belgium & Department of Rehabilitation Sciences, KU Leuven – University of Leuven, Belgium
| | - An Tassenoy
- Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium
| | - Kelly Ickmans
- Pain in Motion International Research Group,
- Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium
- Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Belgium
| | - Dorien Goubert
- Pain in Motion International Research Group,
- Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium
- Department of Rehabilitation Sciences, Ghent University, Ghent, Belgium
| | - C. Paul van Wilgen
- Pain in Motion International Research Group,
- Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium
- Transcare, Transdisciplinairy Painmanagement Centre, Groningen, the Netherlands
| | - Amarins J. Wijma
- Pain in Motion International Research Group,
- Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium
- Transcare, Transdisciplinairy Painmanagement Centre, Groningen, the Netherlands
| | - Kevin Kuppens
- Pain in Motion International Research Group,
- Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium
- Rehabilitation Sciences and Physiotherapy, Faculty of Medicine, Antwerp University, Antwerp, Belgium
| | - Wouter Hoelen
- De Berekuyl, Private practice for physiotherapy in oncology & lymphology, the Netherlands
- European College of Decongestive Lymphatic Therapy, the Netherlands
| | - Astrid Hoelen
- De Berekuyl, Private practice for physiotherapy in oncology & lymphology, the Netherlands
- European College of Decongestive Lymphatic Therapy, the Netherlands
| | - Niamh Moloney
- Department of Health Sciences, Macquarie University, New South Wales, Australia
| | - Mira Meeus
- Pain in Motion International Research Group,
- Rehabilitation Sciences and Physiotherapy, Faculty of Medicine, Antwerp University, Antwerp, Belgium
- Department of Rehabilitation Sciences, Ghent University, Ghent, Belgium
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Brandow AM, Panepinto JA. Clinical Interpretation of Quantitative Sensory Testing as a Measure of Pain Sensitivity in Patients With Sickle Cell Disease. J Pediatr Hematol Oncol 2016; 38:288-93. [PMID: 26907660 PMCID: PMC4856159 DOI: 10.1097/mph.0000000000000532] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Patients with sickle cell disease (SCD) display significantly lower mean/median thermal and mechanical pain thresholds compared with controls. This suggests impaired pain sensitivity where stimuli produce exaggerated pain. Despite these mean/median differences, clinicians need to understand if patients meet criteria for impaired pain sensitivity. We defined thresholds for impaired cold, heat, and mechanical pain sensitivity in SCD patients. Using quantitative sensory testing (QST) we assessed cold, heat, and mechanical pain thresholds in SCD patients and African American controls aged 7 years and above. Impaired pain sensitivity was defined as: (1) cold pain threshold 1 SD above control median threshold; (2) heat pain threshold 1 SD below control median threshold; and (3) mechanical pain threshold 1 SD below control median threshold. Fifty-five SCD patients and 57 controls participated in this study. Impaired pain sensitivity thresholds were: (1) cold: 17.01°C, (2) heat: 43.91°C, and (3) mechanical: 4.42 g. Impaired cold pain sensitivity was the most common finding (63.6%), then heat (60%), and mechanical (38.2%). Impaired pain sensitivity to ≥1 testing modalities occurred in 81.8% of SCD patients. Determining impaired pain sensitivity thresholds increases clinical utility of QST. QST could be a screening tool to phenotype SCD pain, an outcome for pain interventional trials, or guide pain neurobiology investigations.
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Affiliation(s)
- Amanda M. Brandow
- Section of Pediatric Hematology/Oncology, Milwaukee, WI, United States
- Medical College of Wisconsin, Milwaukee, WI, United States
- Children's Research Institute of the Children's Hospital of Wisconsin, Milwaukee, WI, United States
| | - Julie A. Panepinto
- Section of Pediatric Hematology/Oncology, Milwaukee, WI, United States
- Medical College of Wisconsin, Milwaukee, WI, United States
- Children's Research Institute of the Children's Hospital of Wisconsin, Milwaukee, WI, United States
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Abstract
OBJECTIVES The authors investigated if timing of medical treatment is associated with the analgesic effect of pregabalin or placebo in patients with chronic pancreatitis (CP). METHODS Sixty-four patients received pregabalin (150-300 mg twice a day) or matching placebo for 3 consecutive weeks. Responders to treatment were defined as patients with a reduction in clinical pain scores of 30% or greater. Factors associated with timing of pain treatment (ie, duration of CP and opioid usage) were collected at baseline. In addition, other factors that potentially could influence outcome (eg, clinical pain scores prior to study medication, diabetes, and exocrine pancreatic insufficiency) were also included. Conventional groupwise logistic regression and analysis on the individual patient level with a machine learning technique were used to predict treatment response. RESULTS In the conventional statistical analysis duration of CP (odds ratio, 0.9; 95% confidence interval, 0.8-1.1; P = 0.3) and opioid treatment (odds ratio, 1.0; 95% confidence interval, 0.9-1.1; P = 0.6) were not associated with pain relief. In addition, none of the supplementary factors were associated with treatment response (all P > 0.1). Likewise, in the individual patient-level analysis, none of the included variables reached classification accuracies greater than chance level (all P > 0.1). CONCLUSIONS Pregabalin can be added as adjuvant analgesic at any time point during the disease course of CP.
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Marinova M, Rauch M, Mücke M, Rolke R, Gonzalez-Carmona MA, Henseler J, Cuhls H, Radbruch L, Strassburg CP, Zhang L, Schild HH, Strunk HM. High-intensity focused ultrasound (HIFU) for pancreatic carcinoma: evaluation of feasibility, reduction of tumour volume and pain intensity. Eur Radiol 2016; 26:4047-4056. [PMID: 26886904 DOI: 10.1007/s00330-016-4239-0] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2015] [Revised: 11/08/2015] [Accepted: 01/21/2016] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Prognosis of patients with locally advanced pancreatic adenocarcinoma is extremely poor. They often suffer from cancer-related pain reducing their quality of life. This prospective observational study aimed to evaluate feasibility, local tumour response, and changes in quality of life and symptoms in Caucasian patients with locally advanced pancreatic cancer treated by ultrasound-guided high-intensity focused ultrasound (HIFU). METHODS Thirteen patients underwent HIFU, five with stage III, eight with stage IV UICC disease. Ten patients received simultaneous palliative chemotherapy. Postinterventional clinical assessment included evaluation of quality of life and symptom changes using standardized questionnaires. CT and MRI follow-up evaluated the local tumour response. RESULTS HIFU was successfully performed in all patients. Average tumour reduction was 34.2 % at 6 weeks and 63.9 % at 3 months. Complete or partial relief of cancer-related pain was achieved in 10 patients (77 %), five of whom required less analgesics for pain control. Quality of life was improved revealing increased global health status and alleviated symptoms. HIFU treatment was well tolerated. Eight patients experienced transient abdominal pain directly after HIFU. CONCLUSIONS HIFU ablation of pancreatic carcinoma is a feasible, safe and effective treatment with a crucial benefit in terms of reduction of tumour volume and pain intensity. KEY POINTS • US-guided HIFU is feasible and safe for patients with unresectable pancreatic cancer. • HIFU can considerably reduce tumour volume and cancer-related pain. • Patients treated with HIFU experienced significant and lasting reduction of pain intensity. • HIFU has a crucial clinical benefit for patients with pancreatic cancer.
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Affiliation(s)
- Milka Marinova
- Department of Radiology, Medical School & Hospital, University of Bonn, Siegmund-Freud-Str. 25, D-53105, Bonn, Germany.
| | - Maximilian Rauch
- Department of Radiology, Medical School & Hospital, University of Bonn, Siegmund-Freud-Str. 25, D-53105, Bonn, Germany
| | - Martin Mücke
- Department of Palliative Medicine, Medical School & Hospital, University of Bonn, Bonn, Germany.,Department of General Practice and Family Medicine, Medical School & Hospital, University of Bonn, Bonn, Germany
| | - Roman Rolke
- Department of Palliative Medicine, Medical Faculty RWTH Aachen University, Aachen, Germany
| | | | - Jana Henseler
- Department of Radiology, Medical School & Hospital, University of Bonn, Siegmund-Freud-Str. 25, D-53105, Bonn, Germany
| | - Henning Cuhls
- Department of Palliative Medicine, Medical School & Hospital, University of Bonn, Bonn, Germany
| | - Lukas Radbruch
- Department of Palliative Medicine, Medical School & Hospital, University of Bonn, Bonn, Germany
| | - Christian P Strassburg
- Department of Internal Medicine I, Medical School & Hospital, University of Bonn, Bonn, Germany
| | - Lian Zhang
- Clinical Center of Tumor Therapy Chongqing, Chongqing, China
| | - Hans H Schild
- Department of Radiology, Medical School & Hospital, University of Bonn, Siegmund-Freud-Str. 25, D-53105, Bonn, Germany
| | - Holger M Strunk
- Department of Radiology, Medical School & Hospital, University of Bonn, Siegmund-Freud-Str. 25, D-53105, Bonn, Germany
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Gurusamy KS, Lusuku C, Davidson BR, Cochrane Upper GI and Pancreatic Diseases Group. Pregabalin for decreasing pancreatic pain in chronic pancreatitis. Cochrane Database Syst Rev 2016; 2:CD011522. [PMID: 26836292 PMCID: PMC8265874 DOI: 10.1002/14651858.cd011522.pub2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Chronic abdominal pain is one of the major symptoms in people with chronic pancreatitis. The role of pregabalin in people with chronic pancreatic pain due to chronic pancreatitis is uncertain. OBJECTIVES To assess the benefits and harms of pregabalin in people with chronic abdominal pain due to chronic pancreatitis. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2015, issue 6, and MEDLINE, EMBASE, Science Citation Index Expanded, trials registers until June 2015. We also searched the references of included trials to identify further trials. SELECTION CRITERIA We considered only randomised controlled trials (RCT) performed in people with chronic pancreatic pain due to chronic pancreatitis, irrespective of language, blinding, or publication status for inclusion in the review. DATA COLLECTION AND ANALYSIS Two review authors independently identified trials and independently extracted data. We calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) with RevMan 5, based on intention-to-treat analysis. MAIN RESULTS Only one study, funded by Pfizer, met the inclusion criteria for the review. A total of 64 participants (with chronic pain due to chronic pancreatitis) were randomly assigned to receive escalating doses of pregabalin (150 mg per day to 600 mg per day; 34 participants) or matching placebo (30 participants). Participants received pregabalin or placebo for three weeks on an outpatient basis; the outcomes were measured at the end of the treatment (i.e. three weeks from commencement of treatment). Potential participants taking concomitant analgesic medication and expected to stay on a stable regime during the trial were allowed to enter the study. This trial was at low risk of bias. The overall quality of evidence was low or moderate.Only the short-term outcomes were available in this trial. The medium and long-term outcomes, number of work days lost, and length of hospital stay due to admissions for pain control were not available. This trial found that the changes in opiate use (MD -26.00 mg; 95% CI -47.36 to -4.64; participants = 64; moderate-quality evidence), and pain score percentage changes from baseline (MD -12.00; 95% CI -21.82 to -2.18; participants = 64; moderate-quality evidence) were better in participants taking pregabalin compared to those taking placebo. This trial also found that there were more adverse events in participants taking pregabalin compared to those taking placebo (RR 1.71; 95% CI 1.20 to 2.43; participants = 64). The differences between pregabalin and placebo were imprecise for short-term health-related quality of life measured with the EORTC CLQ-30 questionnaire (MD 11.40; 95% CI -3.28 to 26.08; participants = 64; moderate-quality evidence), proportion of people with serious adverse events (RR 1.76; 95% CI 0.35 to 8.96; participants = 64; low-quality evidence), and proportion of people requiring hospital admissions (RR 0.44; 95% CI 0.04 to 4.62; participants = 64; low quality evidence). AUTHORS' CONCLUSIONS Based on low- to moderate-quality evidence, short-term use of pregabalin decreases short-term opiate use, and short-term pain scores, but increases the adverse events compared to placebo, in people with chronic pain due to chronic pancreatitis. The clinical implication of the decreases in short-term opiate use and short-term pain scores is not known.Future trials assessing the role of pregabalin in decreasing chronic pain in chronic pancreatitis should assess the medium- or long-term effects of pregabalin and should include outcomes such as, quality of life, treatment-related adverse events, number of work days lost, number of hospital admissions, and the length of hospital stay, in addition to pain scores, to assess the clinical and socioeconomic impact.
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Affiliation(s)
- Kurinchi Selvan Gurusamy
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryRoyal Free HospitalRowland Hill StreetLondonUKNW3 2PF
| | - Charnelle Lusuku
- The University of NottinghamSchool of MedicineNottinghamUKNG7 2UH
| | - Brian R Davidson
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryRoyal Free HospitalRowland Hill StreetLondonUKNW3 2PF
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Factors Predicting Outcomes After a Total Pancreatectomy and Islet Autotransplantation Lessons Learned From Over 500 Cases. Ann Surg 2015; 262:610-22. [PMID: 26366540 DOI: 10.1097/sla.0000000000001453] [Citation(s) in RCA: 121] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Our objective was to analyze factors predicting outcomes after a total pancreatectomy and islet autotransplantation (TP-IAT). BACKGROUND Chronic pancreatitis (CP) is increasingly treated by a TP-IAT. Postoperative outcomes are generally favorable, but a minority of patients fare poorly. METHODS In our single-centered study, we analyzed the records of 581 patients with CP who underwent a TP-IAT. Endpoints included persistent postoperative "pancreatic pain" similar to preoperative levels, narcotic use for any reason, and islet graft failure at 1 year. RESULTS In our patients, the duration (mean ± SD) of CP before their TP-IAT was 7.1 ± 0.3 years and narcotic usage of 3.3 ± 0.2 years. Pediatric patients had better postoperative outcomes. Among adult patients, the odds of narcotic use at 1 year were increased by previous endoscopic retrograde cholangiopancreatography (ERCP) and stent placement, and a high number of previous stents (>3). Independent risk factors for pancreatic pain at 1 year were pancreas divisum, previous body mass index >30, and a high number of previous stents (>3). The strongest independent risk factor for islet graft failure was a low islet yield-in islet equivalents (IEQ)-per kilogram of body weight. We noted a strong dose-response relationship between the lowest-yield category (<2000 IEQ) and the highest (≥5000 IEQ or more). Islet graft failure was 25-fold more likely in the lowest-yield category. CONCLUSIONS This article represents the largest study of factors predicting outcomes after a TP-IAT. Preoperatively, the patient subgroups we identified warrant further attention.
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