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Lenz FA, Dougherty PM, Meeker TJ, Saffer MI, Oishi K. Neuroscience of the human thalamus related to acute pain and chronic "thalamic" pain. J Neurophysiol 2024; 132:1756-1778. [PMID: 39412562 PMCID: PMC11687836 DOI: 10.1152/jn.00065.2024] [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: 02/16/2024] [Revised: 09/03/2024] [Accepted: 09/16/2024] [Indexed: 11/27/2024] Open
Abstract
The association of posterior thalamic strokes with the presence of chronic "thalamic" pain was described in the early 1900s and revisited in a recent review of these patients. Acute pain in corporal structures is associated with the spinothalamic tract (STT), which originates in the dorsal horn of the spinal cord, whereas that associated with cranial structures is associated with the spinal division of the trigeminal nucleus. These pathways terminate in the ventral posterior nucleus (VP), including its posterior and inferior subnuclei and its core, which is classically associated with tactile and haptic functions. In medial nuclei (medial dorsal and intralaminar) receptive fields are large and stimulation evokes diffuse unpleasant sensations and pain while neurons in these nuclei subserve cognitive processes of attention, alerting, and conditioning. In the lateral nuclei neurons have small receptive and projected fields and high resolution of responses to somatic stimuli. Neurons in the lateral nuclei respond to stimuli producing pain, temperature, and visceral sensations while stimulation evokes similar sensations. Small strokes in VP core versus structures located inferior and posterior are associated with thalamic pain and decreased tactile, painful, and cold sensations and with decreased evoked potentials for painful (laser) heat and median nerve stimulation (electrical). Lesions of VP, but not ventral medial posterior nucleus (VMpo), are associated with thalamic pain, contrary to the recent "disinhibition" model. We review the evidence that the lateral nuclei are associated with multiple processes including tactile, nociceptive, visceral, and thermal content of stimuli, whereas the medial nuclei are related to cognitions about those stimuli.
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Affiliation(s)
- Fred A Lenz
- Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland, United States
| | - Pat M Dougherty
- Department of Pain Medicine, MD Anderson Cancer Center, Houston, Texas, United States
| | - Timothy J Meeker
- Department of Biology, Morgan State University, Baltimore, Maryland, United States
| | - Mark I Saffer
- Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland, United States
| | - Kenichi Oishi
- Department of Radiology, Radiological Science, and Neurology, Johns Hopkins University, Baltimore, Maryland, United States
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Montelaro BM, Ibrahim R, Thames M, Mehta PK. Optimal Medical Therapy for Stable Ischemic Heart Disease: Focus on Anti-anginal Therapy. Med Clin North Am 2024; 108:455-468. [PMID: 38548457 DOI: 10.1016/j.mcna.2023.12.006] [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] [Indexed: 04/02/2024]
Abstract
Chronic coronary disease (CCD) is a major cause of morbidity and mortality worldwide. The most common symptom of CCD is exertional angina pectoris, a discomfort in the chest that commonly occurs during activities of daily life. Patients are dismayed by recurring episodes of angina and seek medical help in preventing or minimizing episodes. Angina occurs when the coronary arteries are unable to supply sufficient blood flow to the cardiac muscle to meet the metabolic needs of the left ventricular myocardium. While lifestyle changes and aggressive risk factor modification play a critical role in the management of CCD, management of angina usually requires pharmacologic therapy. Medications such as beta-blockers, calcium channel blockers, nitrates, ranolazine, and others ultimately work to improve the mismatch between myocardial blood flow and metabolic demand. This manuscript briefly describes the pathophysiologic basis for symptoms of angina, and how currently available anti-anginal therapies contribute to preventing or minimize the occurrence of angina.
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Affiliation(s)
- Brett M Montelaro
- Division of Cardiology, Department of Medicine, J. Willis Hurst Internal Medicine Residency Training Program, Emory University School of Medicine, Atlanta, GA, USA
| | - Rand Ibrahim
- Division of Cardiology, Department of Medicine, J. Willis Hurst Internal Medicine Residency Training Program, Emory University School of Medicine, Atlanta, GA, USA
| | - Marc Thames
- Division of Cardiology, Department of Medicine, Emory University Division of Cardiology, Atlanta, GA, USA
| | - Puja K Mehta
- Division of Cardiology, Department of Medicine, Emory University Division of Cardiology, Atlanta, GA, USA; Women's Translational Cardiovascular Research, Emory Women's Heart Center, Emory Clinical Cardiovascular Research Institute, 1750 Haygood Drive, 2nd Floor, Office #243, Atlanta, GA 30322, USA.
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Cattaneo M, Halasz G, Cattaneo MM, Younes A, Gallino C, Sudano I, Gallino A. The Central Nervous System and Psychosocial Factors in Primary Microvascular Angina. Front Cardiovasc Med 2022; 9:896042. [PMID: 35647077 PMCID: PMC9136057 DOI: 10.3389/fcvm.2022.896042] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 04/14/2022] [Indexed: 01/09/2023] Open
Abstract
Patients diagnosed with ischemia without obstructive coronary artery disease (INOCA) comprise the group of patients with primary microvascular angina (MVA). The pathophysiology underlying ischemia and angina is multifaceted. Differences in vascular tone, collateralization, environmental and psychosocial factors, pain thresholds, and cardiac innervation seem to contribute to clinical manifestations. There is evidence suggesting potential interactions between the clinical manifestations of MVA and non-cardiac conditions such as abnormal function of the central autonomic network (CAN) in the central nervous system (CNS), pain modulation pathways, and psychological, psychiatric, and social conditions. A few unconventional non-pharmacological and pharmacological techniques targeting these psychosocial conditions and modulating the CNS pathways have been proposed to improve symptoms and quality of life. Most of these unconventional approaches have shown encouraging results. However, these results are overall characterized by low levels of evidence both in observational studies and interventional trials. Awareness of the importance of microvascular dysfunction and MVA is gradually growing in the scientific community. Nonetheless, therapeutic success remains frustratingly low in clinical practice so far. This should promote basic and clinical research in this relevant cardiovascular field investigating, both pharmacological and non-pharmacological interventions. Standardization of definitions, clear pathophysiological-directed inclusion criteria, crossover design, adequate sample size, and mid-term follow-up through multicenter randomized trials are mandatory for future study in this field.
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Affiliation(s)
- Mattia Cattaneo
- Cardiology Department, Istituto Cardiocentro Ticino, Lugano, Switzerland
- Human Medicine Department, Università della Svizzera italiana, Lugano, Switzerland
- Cardiovascular Research Unit, Hospital of San Giovanni, Bellinzona, Switzerland
- *Correspondence: Mattia Cattaneo ;
| | - Geza Halasz
- Heart Failure Unit, Guglielmo da Saliceto Hospital, Azienda unità sanitaria locale (AUSL) Piacenza, University of Parma, Parma, Italy
| | - Magdalena Maria Cattaneo
- Human Medicine Department, Università della Svizzera italiana, Lugano, Switzerland
- Cardiovascular Research Unit, Hospital of San Giovanni, Bellinzona, Switzerland
| | - Adel Younes
- Cardiology Department, Istituto Cardiocentro Ticino, Lugano, Switzerland
| | - Camilla Gallino
- Human Medicine Department, Università della Svizzera italiana, Lugano, Switzerland
- Cardiovascular Research Unit, Hospital of San Giovanni, Bellinzona, Switzerland
| | - Isabella Sudano
- Human Medicine Department, University of Zurich, Zurich, Switzerland
- Cardiology Department, University Hospital, University Heart Center Zurich, Zurich, Switzerland
| | - Augusto Gallino
- Human Medicine Department, Università della Svizzera italiana, Lugano, Switzerland
- Cardiovascular Research Unit, Hospital of San Giovanni, Bellinzona, Switzerland
- Human Medicine Department, University of Zurich, Zurich, Switzerland
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Ischemia and no obstructive coronary arteries in patients with stable ischemic heart disease. Int J Cardiol 2022; 348:1-8. [PMID: 34902504 PMCID: PMC8779638 DOI: 10.1016/j.ijcard.2021.12.013] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 11/30/2021] [Accepted: 12/08/2021] [Indexed: 02/03/2023]
Abstract
A large proportion of patients with suspected obstructive coronary artery disease (CAD) is found to have ischemia with no obstructive coronary artery disease (INOCA). Based on current evidence, these patients are at increased risk of adverse cardiovascular events, even though they have no obstructive CAD. Importantly, INOCA is associated with recurrent clinical presentations with chest pain, impaired functional capacity, reduced health-related quality of life, and high healthcare costs. Underlying coronary microvascular dysfunction (CMD), through endothelium-dependent and independent mechanisms contribute to these adverse outcomes in INOCA. While non-invasive and invasive diagnostic testing has typically focused on identification of obstructive CAD in symptomatic patients, functional testing to detect coronary epicardial and microvascular dysfunction should be considered in those with INOCA who have persistent angina. Current diagnostic methods to clarify functional abnormalities and treatment strategies for epicardial and/or microvascular dysfunction in INOCA are reviewed.
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Mehta PK, Wei J, Shufelt C, Quesada O, Shaw L, Bairey Merz CN. Gender-Related Differences in Chest Pain Syndromes in the Frontiers in CV Medicine Special Issue: Sex & Gender in CV Medicine. Front Cardiovasc Med 2021; 8:744788. [PMID: 34869650 PMCID: PMC8635525 DOI: 10.3389/fcvm.2021.744788] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 10/13/2021] [Indexed: 12/30/2022] Open
Abstract
Coronary artery disease (CAD) is the leading cause of morbidity and mortality among both women and men, yet women continue to have delays in diagnosis and treatment. The lack of recognition of sex-specific biological and socio-cultural gender-related differences in chest pain presentation of CAD may, in part, explain these disparities. Sex and gender differences in pain mechanisms including psychological susceptibility, the autonomic nervous system (ANS) reactivity, and visceral innervation likely contribute to chest pain differences. CAD risk scores and typical/atypical angina characterization no longer appear relevant and should not be used in women and men. Women more often have ischemia with no obstructive CAD (INOCA) and myocardial infarction, contributing to diagnostic and therapeutic equipoise. Existing knowledge demonstrates that chest pain often does not relate to obstructive CAD, suggesting a more thoughtful approach to percutaneous coronary intervention (PCI) and medical therapy for chest pain in stable obstructive CAD. Emerging knowledge regarding the central and ANS and visceral pain processing in patients with and without angina offers explanatory mechanisms for chest pain and should be investigated with interdisciplinary teams of cardiologists, neuroscientists, bio-behavioral experts, and pain specialists. Improved understanding of sex and gender differences in chest pain, including biological pathways as well as sociocultural contributions, is needed to improve clinical care in both women and men.
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Affiliation(s)
- Puja K Mehta
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute and Emory Women's Heart Center, Emory University School of Medicine, Atlanta, GA, United States
| | - Janet Wei
- Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, CA, United States
| | - Chrisandra Shufelt
- Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, CA, United States
| | - Odayme Quesada
- Women's Heart Center, The Christ Hospital Heart Institute, Cincinnati, OH, United States
| | - Leslee Shaw
- Department of Radiology, Weill Cornell Medicine, New York, NY, United States
| | - C Noel Bairey Merz
- Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, CA, United States
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Jackson A, Frobert O, Boye Larsen D, Arendt-Nielsen L, Björkenheim A. Patients with symptomatic permanent atrial fibrillation show quantitative signs of pain sensitisation. Open Heart 2021; 8:openhrt-2021-001699. [PMID: 34140311 PMCID: PMC8212408 DOI: 10.1136/openhrt-2021-001699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 06/02/2021] [Indexed: 11/05/2022] Open
Abstract
Objective Most patients with atrial fibrillation (AF) report symptoms, while one-third are asymptomatic. We hypothesised that sensory processing, in particular pain, differs in patients with symptomatic and asymptomatic AF. Methods Thirty individuals with permanent AF (15 symptomatic and 15 asymptomatic) completed the Atrial Fibrillation 6 (AF6) and short form 36 Health Survey questionnaires and underwent quantitative pain sensitisation testing using pressure algometry at the sternum (referred pain area) and the tibialis anterior muscle (generalised pain area). The primary objective was to assess differences in pressure pain thresholds (PPT), temporal summation of pain (TSP) and conditioned pain modulation (CPM) in the two groups. The secondary objective was to determine association of demographic and clinical parameters to measures of pain sensitisation. Results The symptomatic group had lower PPTs at both tibialis (p=0.004) and sternum (p=0.01), and impaired CPM (p=0.025) and facilitated TSP (p=0.008) at the tibialis but not sternum, compared with the asymptomatic group. The AF6 sum score was negatively correlated to PPT on both tibialis (r=−0.50, p=0.005) and sternum (r=−0.42, p=0.02) and positively correlated to TSP on both tibialis (r=0.57, p=0.001) and sternum (r=0.45, p=0.01), but not to CPM. The physical component summary score was positively correlated to the PPT on both tibialis (r=0.52, p=0.003) and sternum (r=0.40, p=0.03) and negatively to TSP on the tibialis (r=−0.53, p=0.003) but not sternum. Conclusions Patients with symptomatic AF exhibit lower pain tolerance than patients with asymptomatic AF, as well as impaired pain inhibitory control and facilitated summation of pain, indicating that pain sensitisation may be of importance in symptomatic AF. Trial registration number NCT04649437.
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Affiliation(s)
- Adam Jackson
- Department of Cardiology, Örebro University Hospital, Sweden, Örebro, Sweden
| | - Ole Frobert
- Department of Cardiology, Faculty of Medicine and Health, Örebro University, Sweden, Örebro, Sweden
| | - Dennis Boye Larsen
- Department of Health Science and Technology and the Center for Sensory-Motor Interaction/Center for Neuroplasticity and Pain, Faculty of Medicine, Aalborg University, Aalborg, Denmark
| | - Lars Arendt-Nielsen
- Department of Health Science and Technology and the Center for Sensory-Motor Interaction/Center for Neuroplasticity and Pain, Faculty of Medicine, Aalborg University, Aalborg, Denmark
| | - Anna Björkenheim
- Department of Cardiology, Faculty of Medicine and Health, Örebro University, Sweden, Örebro, Sweden
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Roy R, Aldiwani H, Darouian N, Sharma S, Torbati T, Wei J, Nelson MD, Shufelt C, Minissian MB, Li L, Merz CNB, Mehta PK. Ambulatory and silent myocardial ischemia in women with coronary microvascular dysfunction: Results from the Cardiac Autonomic Nervous System study (CANS). Int J Cardiol 2020; 316:1-6. [PMID: 32320779 PMCID: PMC8312219 DOI: 10.1016/j.ijcard.2020.04.030] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 02/11/2020] [Accepted: 04/09/2020] [Indexed: 02/01/2023]
Abstract
BACKGROUND Up to two-thirds of patients with obstructive coronary artery disease (CAD) have silent ischemia (SI), which predicts an adverse prognosis and can be a treatment target in obstructive CAD. Over 50% of women with ischemia and no obstructive CAD have coronary microvascular dysfunction (CMD), which is associated with adverse cardiovascular outcomes. We aimed to investigate the prevalence of SI in CMD in order to consider it as a potential treatment target. METHODS 36 women with CMD by coronary reactivity testing and 16 age matched reference subjects underwent 24-h 12-lead ambulatory ECG monitoring (Mortara Instruments) after anti-ischemia medication withdrawal. Ambulatory ECG recordings were reviewed by two-physician consensus masked to subject status for SI measured by evidence of ≥1 minute horizontal or downsloping ST segment depression ≥1.0 mm, measured 80 ms from the J point. RESULTS Demographics, resting heart rate, and systolic blood pressure were similar between CMD and reference subjects. Thirty-nine percent of CMD women had a total of 26 SI episodes vs. 0 episodes in the reference group (p = 0.002). Among these women 13/14 (93%) had SI, and few episodes (3/26, 12%) were symptomatic. Mean HR at the onset of SI was 96 ± 13 bpm and increased to 117 ± 16 bpm during the ischemic episodes. 87% reported symptoms that were not associated with ST depressions. CONCLUSIONS Ambulatory ischemia is prevalent in women with CMD, with a majority being SI, while most reported symptoms were not accompanied by ambulatory ischemia. Clinical trials evaluating anti-ischemic medications should be considered in the CMD population.
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Affiliation(s)
- Rajasree Roy
- Emory Women's Heart Center and Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA, United States of America
| | - Haider Aldiwani
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, LA, CA, United States of America
| | - Navid Darouian
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, LA, CA, United States of America
| | - Shilpa Sharma
- Internal Medicine Residency Program, Massachusetts General Hospital, Boston, MA, United States of America
| | - Tina Torbati
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, LA, CA, United States of America
| | - Janet Wei
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, LA, CA, United States of America
| | - Michael D Nelson
- Department of Kinesiology, University of Texas at Arlington, United States of America
| | - Chrisandra Shufelt
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, LA, CA, United States of America
| | - Margo B Minissian
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, LA, CA, United States of America
| | - Lian Li
- Emory Women's Heart Center and Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA, United States of America
| | - C Noel Bairey Merz
- Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, LA, CA, United States of America
| | - Puja K Mehta
- Emory Women's Heart Center and Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA, United States of America.
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Parsons S, McBeth J, Macfarlane GJ, Hannaford PC, Symmons DPM. Self-reported pain severity is associated with a history of coronary heart disease. Eur J Pain 2014; 19:167-75. [PMID: 24890750 PMCID: PMC4322478 DOI: 10.1002/ejp.533] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/11/2014] [Indexed: 11/08/2022]
Abstract
BACKGROUND Previous studies have found an association between chronic pain and cardiovascular (CV) mortality. OBJECTIVE To explore the relationship between the severity of pain and non-fatal CV disease. METHODS A total of 45,994 adults randomly selected from general practice registers in Manchester and Aberdeen were posted a survey, which included a Chronic Pain Grade questionnaire, pain manikin and questions about lifestyle and medical history. A single component measuring pain severity was extracted using factor analysis. Logistic regression was used to test for an association between quintiles of pain severity and a history of CV disease, adjusting for confounders. RESULTS Of the 15,288 responders, 61% (n = 9357) reported pain for ≥ 1 day in the past month. Compared with the first (lowest) pain severity quintile, the fully adjusted odds ratio for heart attack in the second severity quintile was 1.25 (95% confidence interval 0.68, 2.30); third quintile: 1.65 (0.93, 2.94); fourth quintile: 1.76 (1.00, 3.11) and fifth (highest) quintile 2.47 (1.43, 4.28). Corresponding figures for angina (excluding heart attack) were: 1.79 (0.93, 3.45), 1.91 (1.00, 3.62), 1.03 (0.50, 2.11) and 3.17 (1.71, 5.85). CONCLUSION A history of CV disease is reported more often in those with severe pain than would be expected by chance, even when adjusting for shared risk factors.
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Affiliation(s)
- S Parsons
- Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester, UK
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Do patients with functional chest pain have neuroplastic reorganization of the pain matrix? A diffusion tensor imaging study. Scand J Pain 2014; 5:85-90. [DOI: 10.1016/j.sjpain.2013.11.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2013] [Accepted: 11/25/2013] [Indexed: 02/08/2023]
Abstract
Abstract
Background and aims
In functional chest pain (FCP) of presumed esophageal origin central nervous system hyperexcitability is generally believed to play an important role in pain pathogenesis. However, this theory has recently been challenged. Using magnetic resonance diffusion tensor imaging, the aim was to characterize any microstructural reorganization of the pain neuromatrix in FCP patients.
Methods
13 FCP patients and 20 matched healthy controls were studied in a 3T MR scanner. Inclusion criteria were relevant chest pain, normal coronary angiogram and normal upper gastrointestinal evaluation. Apparent diffusion coefficient (ADC) (i.e. mean diffusivity of water) and fractional anisotropy (FA) (i.e. directionality of water diffusion as a measure of fiber organization) values were assessed in the secondary sensory cortex, cingulate cortex, insula, prefrontal cortex, and amygdala.
Results
Overall, including all regions, no difference in ADC and FA values was found between the patients and controls (P = 0.79 and P = 0.23, respectively). Post-hoc tests revealed no difference in ADC and FA values of the individual regions. However, a trend of patients having increased ADC in the mid insula grey matter and increased FA in the mid insula white matter was observed (both P = 0.065).
Conclusions
This explorative study suggests that microstructural reorganization of the central pain neuromatrix may not be present in well-characterized FCP patients.
Implications
This finding, together with recent neurophysiologal evidence, challenges the theory of visceral hypersensitivity due to changes in the central nervous system in FCP patients.
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Hoff DAL, Krarup AL, Lelic D, Olesen SS, Dimcevski G, Hansen TM, Brock C, Hatlebakk JG, Drewes AM. Central response to painful electrical esophageal stimulation in well-defined patients suffering from functional chest pain. Neurogastroenterol Motil 2013; 25:e718-e727. [PMID: 23965033 DOI: 10.1111/nmo.12196] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2013] [Accepted: 07/03/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND Functional chest pain (FCP) of presumed esophageal origin is considered a common cause for chest pain in which central nervous system hyperexcitability is thought to play an important role. We aimed to compare cerebral responses with painful esophageal stimuli between FCP patients and healthy subjects (HS). METHODS Thirteen patients with FCP (seven females, mean age 50.4 ± 7.5 years) and 15 HS (eight females, mean age 49.1 ± 12.9 years) were enrolled. Inclusion criteria consisted of typical chest pain, normal coronary angiogram, and normal upper gastrointestinal evaluation. Electrical stimulations evoking the pain threshold were applied in the distal esophagus, while cortical evoked potentials were recorded from the scalp. Pain scores, resting electroencephalogram (EEG), evoked potential characteristics and brain electrical sources to pain stimulation were compared between groups. KEY RESULTS No differences were seen between patients and HS regarding (i) pain thresholds (patients: 20.1 ± 7.4 mA vs HS: 22.4 ± 8.3 mA, all P > 0.05), (ii) resting-EEG (P > 0.05), (iii) evoked brain potential latencies (N2: patients 181.7 ± 25.7 mS vs HS 182.2 ± 25.8 mS, all P > 0.05) and amplitudes (N2P2: patients 8.2 ± 7.2 μV vs HS: 10.1 ± 3.4 μV, all P > 0.05), (iv) topography (P > 0.05), and (v) brain source location (P > 0.05). CONCLUSIONS & INFERENCES No differences in activation of brain areas to painful esophageal stimulation were seen in this group of well characterized patients with FCP compared with sex- and age-matched HS. The mechanism of pain in FCP and whether it originates in the esophagus remains unsolved.
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Affiliation(s)
- D A L Hoff
- Department of Medicine, Division of Gastroenterology and Hepatology, Aalesund Hospital, Aalesund, Norway
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11
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Banerjee R, Pratap N, Kalpala R, Reddy DN. Effect of electrical stimulation of the lower esophageal sphincter using endoscopically implanted temporary stimulation leads in patients with reflux disease. Surg Endosc 2013; 28:1003-9. [PMID: 24170067 DOI: 10.1007/s00464-013-3271-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2013] [Accepted: 10/06/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND Electrical stimulation therapy (EST) has been shown to increase lower esophageal sphincter (LES) pressure in animals; however, data on the effect of EST on LES pressure in patients with gastroesophageal reflux disease (GERD) are lacking. OBJECTIVE The aim of our study was to investigate the effect of EST on LES pressure and esophageal function in patients with GERD. METHODS Patients with a diagnosis of GERD responsive to proton pump inhibitors (PPIs), increased esophageal acid on 24-h pH monitoring off GERD medications, basal LES pressure >5 mmHg, hernia <2 cm and esophagitis <LA grade B were included. A temporary pacemaker lead was placed endoscopically in the LES by creating a 3 cm submucosal tunnel, secured to the esophagus using endoscopic clips along the body of the lead and exteriorized nasally. EST was delivered 6-12 h post-implant per protocol using (i) short-pulse 200 μs, 20 Hz, and (ii) intermediate-pulse 3 ms, 20 Hz, each for 20 min at varying amplitudes. High-resolution manometry was performed pre-, during and post-EST. Symptoms of heartburn, chest or abdominal pain and dysphagia pre-, during and post-stimulation and 7 days post-procedure were recorded. Continuous cardiac monitoring was performed during and after the EST to evaluate any effect of EST on cardiac rhythm. RESULTS Six male patients (mean age 34.6 years) underwent successful endoscopic lead implantation; the first patient had premature lead dislodgement and did not undergo EST. The remaining five patients underwent successful EST. All patients had a significant increase in LES pressure with all sessions of EST. There was no effect on swallow-induced LES relaxation, And there were no EST-related adverse symptoms or any cardiac rhythm abnormalities. CONCLUSIONS In patients with GERD, short-term EST delivered using electrodes endoscopically implanted in the LES results in a significant increase in LES pressure without affecting patients' swallow function or causing any adverse symptoms or cardiac rhythm disturbances. EST may offer a novel therapy to patients with GERD.
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Affiliation(s)
- Rupa Banerjee
- Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad, 500 082, India,
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12
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Rosen SD. From heart to brain: the genesis and processing of cardiac pain. Can J Cardiol 2012; 28:S7-19. [PMID: 22424286 DOI: 10.1016/j.cjca.2011.09.010] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2011] [Revised: 09/15/2011] [Accepted: 09/15/2011] [Indexed: 01/12/2023] Open
Abstract
Angina pectoris is important because of its association with heart disease and risk of death. Historically after Heberden's account of angina in 1772, the association of pain with coronary artery disease quickly followed. Within a few years, Burns suggested an etiological role for ischemia. Subsequently, theories of differential myocardial stretch dominated thinking until Lewis' chemical hypothesis in 1932, in which the local release of chemical substances during ischemia was seen as the cause of pain. This review considers how ischemia at the tissue level triggers activation of afferent nociceptive pain fibres. The afferent projections of sympathetic and vagal afferent fibres are described, with a number of methodologies cited (eg, injection of pseudorabies virus into the heart with mapping of the retrograde viral transport pathways; and elevation of neuronal c-fos synthesis in brain regions activated by capsaicin application to the heart). Our own functional neuroimaging studies of angina are also reviewed. There are 2 intriguing features of angina. The first is the poor correlation between symptoms and extent of coronary disease. The spectrum ranges from entirely silent myocardial ischemia to that of a functional pain syndrome--the 'sensitive heart'--of cardiac syndrome X. An even more difficult aspect is the wide variability in symptoms experienced by an individual patient. A new paradigm is presented which, besides considering myocardial oxygen supply/demand imbalance, also draws insights from the broader field of pain research. Neuromodulation applies at multiple levels of the neuraxis--peripheral nerves, spinal cord, and brain--and it invites exploitation, whether pharmacological or electrical, for the benefit of the cardiac patient in pain.
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Affiliation(s)
- Stuart D Rosen
- National Heart and Lung Institute, Imperial College, London, United Kingdom.
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13
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Arnold SV, Spertus JA, Ciechanowski PS, Soine LA, Jordan-Keith K, Caldwell JH, Sullivan MD. Psychosocial modulators of angina response to myocardial ischemia. Circulation 2009; 120:126-33. [PMID: 19564560 DOI: 10.1161/circulationaha.108.806034] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Although angina is often caused by atherosclerotic obstruction of the coronary arteries, patients with similar amounts of myocardial ischemia may vary widely in their symptoms. We sought to compare clinical and psychosocial characteristics associated with more frequent angina after adjusting for the amount of inducible ischemia. METHODS AND RESULTS From 2004 to 2006, 788 consecutive patients undergoing single-photon emission computed tomography stress perfusion imaging at 2 Seattle hospitals were assessed for their frequency of angina over the previous 4 weeks with the Seattle Angina Questionnaire and for a broad range of psychosocial characteristics. Among patients with demonstrable ischemia on single-photon emission computed tomography (summed difference score >or=2; n=191), angina frequency was categorized as none (Seattle Angina Questionnaire score=100; n=68), monthly (score=61 to 99; n=66), and weekly or daily (score=0 to 60; n=57). Using multivariable ordinal logistic regression, increasing angina was significantly associated with a history of coronary revascularization (odds ratio 2.24, 95% confidence interval 1.19 to 4.19), anxiety (odds ratio 4.72, 95% confidence interval 1.91 to 11.66), and depression (odds ratio 3.12, 95% confidence interval 1.45 to 6.69) after adjustment for the amount of inducible ischemia. CONCLUSIONS Among patients with a similar burden of inducible ischemia, a history of coronary revascularization and current anxiety and depressive symptoms were associated with more frequent angina. These results support the study of angina treatment strategies that aim to reduce psychosocial distress in conjunction with efforts to lessen myocardial ischemia.
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14
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Dimcevski G, Sami SAK, Funch-Jensen P, Le Pera D, Valeriani M, Arendt-Nielsen L, Drewes AM. Pain in chronic pancreatitis: the role of reorganization in the central nervous system. Gastroenterology 2007; 132:1546-56. [PMID: 17408654 DOI: 10.1053/j.gastro.2007.01.037] [Citation(s) in RCA: 127] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2006] [Accepted: 01/04/2007] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS In various chronic pain conditions cortical reorganization seems to play a role in the manifestations. The aim of this study was to investigate cortical reorganization in patients with pain caused by chronic pancreatitis. METHODS Twelve healthy subjects and 10 patients with chronic pancreatitis were included. The esophagus, stomach, and duodenum were stimulated electrically at the pain threshold using a nasal endoscope. The electroencephalogram was recorded from 64 surface electrodes and event-related brain potentials (EPs) were obtained. RESULTS As compared with healthy subjects, the patient group showed decreased latencies of the early EP components (N1, P < .001; P1, P = .02), which is thought to reflect the exogenous brain pain processing specifically. Source analysis showed that the dipolar activities corresponding to the early EPs were located consistently in the bilateral insula, in the anterior cingulate gyrus, and in the bilateral secondary somatosensory area. The bilateral insular dipoles were localized more medial in the patient group than in the healthy subjects after stimulation of all 3 gut segments (P < .01). There also were changes in the cingulate cortex where the neuronal source was more posterior in patients than in controls to stimulation of the esophagus (P < .05). CONCLUSIONS The findings indicate that pain in chronic pancreatitis leads to changes in cortical projections of the nociceptive system. Such findings also have been described in somatic pain disorders, among them neuropathic pain. Taken together with the clinical data this suggests a neuropathic component in pancreatic pain, which may influence the approach to treatment.
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Affiliation(s)
- Georg Dimcevski
- Center for Visceral Biomechanics and Pain, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
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15
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Drewes AM, Pedersen J, Reddy H, Rasmussen K, Funch-Jensen P, Arendt-Nielsen L, Gregersen H. Central sensitization in patients with non-cardiac chest pain: a clinical experimental study. Scand J Gastroenterol 2006; 41:640-9. [PMID: 16754535 DOI: 10.1080/00365520500442559] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Patients with non-cardiac chest pain (NNCP) suffer from unexplained and often intractable pain which can pose a major clinical problem. The aim of this study was to investigate nociceptive processing in NNCP patients and their response to experimentally acid-induced oesophageal hyperalgesia using a multimodal stimulation protocol. MATERIAL AND METHODS Ten highly selected patients with NCCP (mean age 43 years, 1 M) were compared with an age- and gender-matched group of 20 healthy subjects. After preconditioning, the distal oesophagus was painfully distended with a balloon using "impedance planimetry". This method assesses the luminal cross-sectional area of the oesophagus based on the electrical impedance of the fluid inside the balloon. The baseline distensions were done before and after pharmacological relaxation of the smooth muscle with 20 mg butylscopolamine. After baseline distensions, a series of up to 10 mechanical stimuli was performed (temporal summation). The stimulations were repeated after sensitization of the oesophagus induced by acid perfusion. The sensory intensities were assessed during the stimulations and the referred pain area was mapped. RESULTS At baseline distensions, no differences were seen between patients and controls before and after relaxation of the smooth muscles. The patients tolerated fewer repeated distensions than controls (4.8+/-0.5 versus 9.1+/-0.9; p=0.04) and had an increased size of the referred pain areas to the mechanical stimulations (32.9+/-6.2 versus 64.9+/-18.3 cm2; p=0.01). After sensitization with acid, the patients developed hyperalgesia (p<0.001), whereas no significant changes were seen in controls. CONCLUSIONS NCCP patients showed facilitated central pain mechanisms (temporal summation and visceral hyperalgesia after sensitization). This could be used in the diagnosis and understanding of the symptoms in these patients.
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Affiliation(s)
- Asbjørn Mohr Drewes
- Centre for Visceral Biomechanics and Pain, Department of Gastroenterology, Aalborg Hospital, Aalborg, Denmark.
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16
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Drewes AM, Arendt-Nielsen L, Funch-Jensen P, Gregersen H. Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain. World J Gastroenterol 2006; 12:2806-17. [PMID: 16718803 PMCID: PMC4087795 DOI: 10.3748/wjg.v12.i18.2806] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy.
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Affiliation(s)
- Asbjørn Mohr Drewes
- Center for Visceral Biomechanics and Pain, Department of Medical Gastroenterology, Aalborg University Hospital, DK-9000 Aalborg, Denmark.
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17
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Drewes AM, Reddy H, Staahl C, Pedersen J, Funch-Jensen P, Arendt-Nielsen L, Gregersen H. Sensory-motor responses to mechanical stimulation of the esophagus after sensitization with acid. World J Gastroenterol 2005; 11:4367-74. [PMID: 16038036 PMCID: PMC4434664 DOI: 10.3748/wjg.v11.i28.4367] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus. The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization.
METHODS: Thirty healthy subjects were included. Distension of the distal esophagus with a balloon was performed before and after perfusion with 0.1 mol/L hydrochloric acid for 30 min. An impedance planimetry system was used to measure cross-sectional area, volume, pressure, and tension during the distensions. A new model allowed evaluation of the phasic contractions by the tension during contractions as a function of the initial muscle length before the contraction (comparable to the Frank-Starling law for the heart). Length-tension diagrams were used to evaluate the muscle tone before and after relaxation of the smooth muscle with butylscopolamine.
RESULTS: The sensitization resulted in allodynia and hyperalgesia to the distension volumes, and the degree of sensitization was related to the infused volume of acid. Furthermore, a nearly 50% increase in the evoked referred pain was seen after sensitization. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions, but the muscle tone did not change.
CONCLUSION: Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions. The new model can be used to study abnormal sensory-motor mechanisms in visceral organs.
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Affiliation(s)
- Asbjørn-Mohr Drewes
- Center for Biomechanics and Pain, Department of Medical Gastroenterology, Aalborg Hospital, DK-9000 Aalborg, Denmark.
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18
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Saab CY, Park YC, Al-Chaer ED. Thalamic modulation of visceral nociceptive processing in adult rats with neonatal colon irritation. Brain Res 2004; 1008:186-92. [PMID: 15145755 DOI: 10.1016/j.brainres.2004.01.083] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/25/2004] [Indexed: 01/24/2023]
Abstract
Visceral pain originates from visceral organs in response to a noxious stimulus which, if prolonged, may lead to chronic changes in the neural network mediating visceral nociception. For instance, colon inflammation enhances the responses of neurons in the thalamus to colorectal distension (CRD), whereas lesion in the dorsal column (DC) reverses this neuronal sensitization, suggesting that the thalamus and the DC play major roles in chronic visceral pain. In this study, we used adult rats sensitized with neonatal painful colon irritation to reveal the contribution of the thalamus and the DC to neuronal hyperexcitability in a model of chronic visceral pain. We recorded the responses of lumbosacral neurons to CRD in control rats and in rats with colon irritation following stimulation or inactivation of the thalamus, and after DC lesion. Our results show that, first, neuronal responses to CRD decreased following thalamic stimulation in control rats, whereas, in rats with colon irritation, responses either decreased or increased; second, DC lesion attenuated or enhanced these effects in the positively or in the negatively modulated group of neurons, respectively; third, lidocaine injection in the thalamus reduced the responses to CRD in some of the neurons recorded in rats with colon irritation, but had no effect on those in control rats. Therefore, it is reasonable to speculate that plasticity in rats with colon irritation that may underlie chronic pain is sustained by feedback loops ascending in the DC and engaging the thalamus.
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Affiliation(s)
- Carl Y Saab
- Department of Neurology, School of Medicine, Yale University, New Haven, CT, USA
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19
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Abstract
This case study demonstrates that patients with NCCP can be subclassified on the basis of sensory responsiveness and neurophysiologic profiles. This approach identifies specific abnormalities within the CNS processing of esophageal sensation in individual patients, allowing us to objectively differentiate those with sensitized esophageal afferents from those that are hypervigilant to esophageal sensations. The importance of this approach is to underline that NCCP comprises a heterogeneous group of patients. and only when we have defined the phenotype of this condition and identified groups of patients with specific CNS abnormalities will it be possible to perform clinical studies aimed at answering specific hypotheses. The development of a comprehensive pathophysiologic model that identifies the specific causes of symptoms in patients with esophageal hypersensitivity will allow the future management strategies of these patients to be targeted more specifically and efficiently. This will have great benefits to patients'well-being and health care use.
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Affiliation(s)
- Anthony R Hobson
- Section of Gastrointestinal Sciences, University of Manchester, Hope Hospital, Eccles Old Road, Salford, M6 8HD, UK.
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20
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Drewes AM, Gregersen H, Arendt-Nielsen L. Experimental pain in gastroenterology: a reappraisal of human studies. Scand J Gastroenterol 2003; 38:1115-30. [PMID: 14686714 DOI: 10.1080/00365520310004399] [Citation(s) in RCA: 135] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- A M Drewes
- Center for Visceral Biomechanics and Pain, Dept. of Medical Gastroenterology, Aalborg University Hospital, Denmark.
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21
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22
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Abstract
GOALS Review of research directions in the etiology, evaluation, and treatment of patients with noncardiac chest pain. The author proposes a combined practical approach to noncardiac chest pain that incorporates these findings, which is useful in a clinical practice setting. BACKGROUND Several major schools of thought have emerged in the etiology of noncardiac chest pain: acid reflux, motor disorder, altered pain threshold/hypersensitivity, and association with psychiatric dysfunction. There is significant overlap among these. Occult gastroesophageal reflux disease (GERD) is more common than motor disorders and is found in 30% to 40% of these patients; a subset has hypersensitivity, with a normal pH profile. Esophageal motility testing and endoscopy have a more limited role than 24-hour pH testing. Impedance planimetry and balloon sensory provocative testing remain research tools. Provocative testing with hydrochloric acid or edrophonium is less helpful than pH monitoring. Gastroesophageal reflux disease-induced chest pain requires high-dose long-term proton pump inhibitors (PPIs): at least 4 to 8 weeks. Psychotropics are superior to placebo, both in patients with and without psychiatric dysfunction. RESULTS The author found combined PPIs and psychotropics helpful in patients with esophageal hypersensitivity and GERD, although supporting data is scant. CONCLUSIONS A brief 1-week high-dose PPI challenge, i.e., omeprazole test, may be cost-effective in a primary care setting. However, this approach may not be useful in a referral setting, where pH data and diary assessment of associated symptoms provide useful management help. A behavioral model approach, with early emphasis on patient education, integrated with physiologic data helps the most.
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Affiliation(s)
- V Alin Botoman
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, Florida 33331, USA.
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23
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Zachariae R, Melchiorsen H, Frøbert O, Bjerring P, Bagger JP. Experimental pain and psychologic status of patients with chest pain with normal coronary arteries or ischemic heart disease. Am Heart J 2001; 142:63-71. [PMID: 11431658 DOI: 10.1067/mhj.2001.115794] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND The cause of chest pain in patients with a normal coronary angiogram (NCA) remains an enigma. Also, it is unclear whether psychosocial factors play a role in the etiology of chest pain in these patients. The objective of the current study was to compare psychosocial factors, clinical pain, and responses to experimental pain in NCA patients, patients with ischemic heart disease (IHD), and healthy control subjects. METHODS Pain intensity, threshold, and tolerance to cold pressor pain were assessed in 30 NCA patients, 30 IHD patients, and 30 healthy control subjects matched for age, sex, and sociodemographic factors. All subjects completed questionnaires measuring a number of psychosocial factors, including stress, anxiety, depression, extroversion, and neuroticism. NCA and IHD patients also completed questionnaires assessing clinical pain responses and pain-coping strategies. RESULTS With the exception of a lower tolerance to cold pressor pain of IHD patients (P <.05), no significant differences were found between NCA and IHD patients with respect to other clinical pain measures, psychosocial measures, pain-coping strategies, and other pain-related behaviors. Healthy control subjects differed significantly (P <.05) from both IHD and NCA patients with respect to maximum cold pressor pain, depression, and state anxiety and from IHD patients with respect to intensity of cold pressor pain, threshold to cold pressor pain, and perceived stress. CONCLUSIONS The results suggest that higher scores on various psychosocial measures in both chest pain groups are related to their pain, rather than being the cause of pain, and do not support a psychogenic explanation for chest pain in the presence of normal coronary arteries.
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Affiliation(s)
- R Zachariae
- Institute of Psychology, Aarhus University, Aarhus, Denmark
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24
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Rogacka D, Guzik P, Wykretowicz A, Rzeźniczak J, Dziarmaga M, Wysocki H. Effects of trimetazidine on clinical symptoms and tolerance of exercise of patients with syndrome X: a preliminary study. Coron Artery Dis 2000; 11:171-7. [PMID: 10758819 DOI: 10.1097/00019501-200003000-00012] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Trimetazidine diminishes angina and improves tolerance of exercise of patients with ischemic heart disease, and has no influence on blood pressure and heart rate. OBJECTIVE To determine the effect of trimetazidine on angina symptoms and exercise tolerance in patients with syndrome X. METHODS We investigated the effect of trimetazidine on the clinical symptoms and tolerance of exercise of 34 patients (20 women and 14 men, aged 32-60 years) with syndrome X (angina pectoris, positive result of exercise test, and normal coronary angiogram). The exercise test was performed before initiation of oral administration of trimetazidine therapy (20 mg three times a day) and 1 and 6 months thereafter. RESULTS We obtained negative results of exercise treadmill tests for four patients (11.76%) after 1 month and five patients (14.71%) after 6 months of trimetazidine treatment. There was also a decrease in the incidence of effort angina after 6 months of treatment (26 patients or 76.47% before treatment versus 13 patients or 38.23% after 6 months of treatment). The drug had no significant influence on the heart rate and blood pressure. The duration for which patients could exercise was significantly prolonged by 1 month (652.9 +/- 206.2 versus 563.4 +/- 190.4 s, P = 0.0047) and 6 months (650.3 +/- 207.8 s, P = 0.0094) of treatment with trimetazidine. CONCLUSION Treatment with trimetazidine decreases signs of angina during exercise and improves tolerance of exercise of patients with syndrome X.
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Affiliation(s)
- D Rogacka
- Department of Internal Medicine, University School of Medical Sciences, Poznań, Poland
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25
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Kanazawa M, Nomura T, Fukudo S, Hongo M. Abnormal visceral perception in patients with functional dyspepsia: use of cerebral potentials evoked by electrical stimulation of the oesophagus. Neurogastroenterol Motil 2000; 12:87-94. [PMID: 10744446 DOI: 10.1046/j.1365-2982.2000.00183.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Altered visceral perception is thought to be included in the pathogenesis of functional dyspepsia. However, in previous studies, the assessment of visceral perception has been based solely on patients self-reported symptoms. Cerebral evoked potential (EP), either by mechanical or electrical stimulation (ES) of the visceral organ, is used to evaluate visceral perception via afferent neural pathways. In this study, we investigated the visceral perception in patients with functional dyspepsia by EP to eliminate the possibility of self-reported bias. EP responses were recorded by oesophageal ES at 37 cm from the nostril in 14 patients with functional dyspepsia and 14 normal healthy control subjects. Threshold levels of perception, peak latencies and peak-to-peak amplitudes of EP were evaluated. There was no difference in the sensory threshold between the dyspeptic patients and the control subjects (median 6 mA, range 2-12 mA, vs. 8 mA, range 6-14 mA; P= 0.09). There was a strong trend towards a decreased discomfort threshold in the patients when compared to the control subjects (median 14 mA, range 6-24 mA vs. 20 mA, range 14-26 mA; P = 0.05). The latency of the later EP peak (N2) among the patients (154 ¿ 4 ms) was significantly shorter than that of the control subjects (171 ¿ 3 ms, P < 0.01) although there was no difference between the earlier peaks (Ni and P1). There was also no difference in the amplitudes (Ni/Pi and P1/N2) of EP between the patients and the control subjects. Half of the patients (seven out of 14) complained of nausea during ES but the control subjects were unaffected. The latency of the first EP peak (Ni) in the patients with nausea was significantly shorter (66 ¿ 3 ms) than that of the patients without nausea (79 ¿ 4 ms, P 0.05) or among the control subjects (80 ¿ 3 ms, P < 0.05). These results suggest that dyspeptic patients may recruit a greater number of fast conducting myelinated nerve fibres that convey visceral afferent impulses to the brain and/or that dyspeptic patients may have an altered central processing of the visceral perception. We conclude that EP recording by oesophageal ES provides an objective measurement of altered visceral perception in patients with functional dyspepsia.
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Affiliation(s)
- M Kanazawa
- Department of Psychosomatic Medicine, Tohoku University School of Medicine, Sendai, Japan
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26
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Shi G, Tatum RP, Joehl RJ, Kahrilas PJ. Esophageal sensitivity and symptom perception in gastroesophageal reflux disease. Curr Gastroenterol Rep 1999; 1:214-9. [PMID: 10980952 DOI: 10.1007/s11894-999-0037-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Patients with gastroesophageal reflux disease (GERD) experience a wide spectrum of symptoms, varying both in quality and severity. This review summarizes clinical observations of esophageal sensitivity and symptom perception in GERD patients. The Bernstein test, although lacking standardization, remains a useful tool in determining esophageal sensitivity to acid stimuli. Ambulatory 24-hour pH monitoring with symptom event marking and subsequent symptom-reflux correlation between acid reflux events and esophageal symptomatology now provides an alternative method for establishing esophageal acid sensitivity. The intraesophageal balloon distention test (IEBD) was developed to assess esophageal sensitivity to mechanical stimuli. Variants of each of these tests have been applied to the evaluation of uncomplicated GERD patients and patients with esophagitis and Barrett's metaplasia, who generally demonstrate less esophageal sensitivity than the former group. Studies using these methods have demonstrated increased esophageal sensitivity in patients with esophageal chest pain and have also identified a subset of patients with esophageal symptoms yet normal esophageal acid exposure, a condition referred to as "hypersensitive esophagus." The Bernstein test, 24-hour pH monitoring with symptom assessment, and IEBD have each contributed to our understanding of esophageal pain syndromes; it is hoped that future work in this area will lead to improved and more specific therapy for these patients.
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Affiliation(s)
- G Shi
- Northwestern University Medical School, Division of Gastroenterology and Hepatology, Department of Medicine, Passavant Pavilion, Suite 746, 303 East Superior Street, Chicago, IL 60611-3053, USA
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27
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Abstract
Syndrome X is likely to be caused by a dysfunction of small coronary arteries. Several authors suggested that an increased adrenergic activity could be involved in the pathogenesis of syndrome X, but studies investigating this topic by indirect methods led to conflicting results. We directly investigated cardiac sympathetic nerve function in syndrome X by myocardial radionuclide studies with 123I-metaiodobenzylguanidine (MIBG). Twelve syndrome X patients and 10 healthy controls were enrolled in the study. Cardiac MIBG uptake was assessed calculating the heart/mediastinum (H/M) ratio and a semiquantitative MIBG uptake score. Cardiac MIBG images were normal in all but 1 of controls (10%). Conversely, abnormalities in cardiac MIBG uptake were found in 9 syndrome X patients (75%, p < 0.01). In 5 patients the heart was totally or almost totally invisible on radionuclide MIBG images, while regional defects were found in other 4 patients. The H/M ratio was lower and cardiac MIBG uptake score strikingly higher in syndrome X patients. At 3 hours the H/M ratio was 1.70 +/- 0.6 in patients and 2.19 +/- 0.3 in controls (p = 0.03), while MIBG uptake score was 36.7 +/- 31 and 4.0 +/- 2.5 (p = 0.003) in the 4 groups, respectively. There were no differences between patients and controls in lung and salivary MIBG uptake. Reversible perfusion defects on stress thallium scintigraphy were found in 5 syndrome X patients (45%), all of whom also had abnormal MIBG scintigrams, while all 3 patients with normal MIBG scintigraphy also had normal thallium images. Thus, the function of efferent cardiac adrenergic nerve fibers is strongly impaired in the majority (i.e., 75%) of syndrome X patients. This abnormal function likely contributes significantly to the pathophysiologic and clinical features of syndrome X. We speculate that also the increased perception of cardiac pain reported in these patients could be an expression of the abnormal function of cardiac nerves, reflecting alterations of afferent nociceptive cardiac nerve fibers, as the abnormalities in MIBG uptake reflect alterations of efferent cardiac adrenergic nerve fibers.
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Affiliation(s)
- G A Lanza
- Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Roma, Italy
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Atienza F, Velasco JA, Brown S, Ridocci F, Kaski JC. Assessment of quality of life in patients with chest pain and normal coronary arteriogram (syndrome X) using a specific questionnaire. Clin Cardiol 1999; 22:283-90. [PMID: 10198738 PMCID: PMC6655793 DOI: 10.1002/clc.4960220406] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/1998] [Accepted: 10/26/1998] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Prognosis in patients with syndrome X (chest pain and normal coronary arteriograms) is good; however, persistent chest pain and functional disability are common in these patients. Accurate assessment of quality of life may be useful for patient management. AIM The quality of life status in patients with syndrome X was assessed using a specific questionnaire. This questionnaire was developed and validated for the assessment of quality of life in patients with typical chest pain despite normal coronary arteriograms. METHODS Ninety consecutive patients were invited to complete both the questionnaire (on two occasions within 2 weeks) and a standardized angina dairy. Fully completed questionnaires were received from 66 (73%) patients (mean age 58 +/- 8 years, 55 women). RESULTS Answers were scored according to a grading system where higher scores indicate worse quality of life. We observed that total scores increased with severity of angina (Canadian Class I, 38 +/- 16, II: 93 +/- 29, III-IV, 119 +/- 23; p < 0.001) and correlated with both the number and the severity of chest pain episodes (r = 0.50-0.66: p < 0.001). In patients who remained clinically stable (n = 37) during the 2-week assessment, test-retest analysis showed no score differences (87 +/- 30 vs. 81 +/- 30; p = 0.1), while total score increased in patients (n = 24) whose symptoms worsened (108 +/- 31 vs. 116 +/- 31; p < 0.02) and was reduced in those (n = 5) whose symptoms improved (55 +/- 37 vs. 39 +/- 28; p < 0.04). CONCLUSION Our study shows that quality of life is significantly impaired in patients with syndrome X and that the specific questionnaire used for assessment is a reliable and sensitive tool for the evaluation of quality of life in patients with chest pain and normal coronary arteriograms.
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Affiliation(s)
- F Atienza
- Cardiology Department, Hospital General Universitario, Valencia, Spain
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29
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Frøbert O, Fossgreen J, Søndergaard-Petersen J, Hede J, Bagger JP. Musculo-skeletal pathology in patients with angina pectoris and normal coronary angiograms. J Intern Med 1999; 245:237-46. [PMID: 10205585 DOI: 10.1046/j.1365-2796.1999.0433e.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
PURPOSE To evaluate the role of the musculo-skeletal apparatus in patients with angina pectoris despite normal coronary angiograms. DESIGN A survey of patients and controls investigated by blinded observers. SETTING A tertiary cardiologic referral centre. SUBJECTS Thirty women and 18 men (mean age 52.9 years) with chest pain of an average duration of 3 years and 11 months were investigated. All had normal resting electrocardiograms. No patients showed evidence of left ventricular hypertrophy or valvular heart disease on echocardiography and all had a normal coronary angiogram. All had left ventricular ejection fraction > 50%, and none had signs of coronary vasospasm. Eighteen healthy persons (10 women and eight men, mean age 51.2 years) served as controls. MAIN OUTCOME MEASURES The group frequency of chest wall complaints, spinal radiograph and physical examination findings; pressure pain thresholds. RESULTS The patients had significantly more complaints of pain from the neck, chest, and thoracic spine, and sensations and pain radiating to the arms than the controls. The patients had more degenerative findings on radiograph than the controls, mainly at levels C4-C7. Physical examination showed that abnormal findings were significantly more frequent in patients than in the control group in the anterior and posterior chest wall, in the spine at levels Th1-Th6 and in the muscles of the neck and shoulder girdle. There were no statistically significant differences in pain thresholds or in neurological examination. CONCLUSION The musculo-skeletal abnormalities observed in the patients could include reflex mechanisms. Whether the abnormal findings are mainly responsible for the angina pectoris symptoms or merely epiphenomena warrants further study.
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Affiliation(s)
- O Frøbert
- Department of Cardiology, Skejby Hospital, University Hospital Aarhus, Denmark.
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Affiliation(s)
- Q Aziz
- Department of Medicine, Section of Gastroenterology, University of Manchester, England
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Pasceri V, Lanza GA, Buffon A, Montenero AS, Crea F, Maseri A. Role of abnormal pain sensitivity and behavioral factors in determining chest pain in syndrome X. J Am Coll Cardiol 1998; 31:62-6. [PMID: 9426019 DOI: 10.1016/s0735-1097(97)00421-x] [Citation(s) in RCA: 65] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVES We sought to investigate whether patients with syndrome X have an abnormal perception of cardiac pain. BACKGROUND Previous studies have reported an increased sensitivity to potentially painful cardiac stimuli in patients with syndrome X. However, it is not clear whether this increase is due to an increased perception of pain or to an enhanced tendency to complain. METHODS We assessed cardiac sensitivity to pain in 16 patients with syndrome X and 15 control subjects by performing right atrial and ventricular pacing with increasing stimulus intensity (1 to 10 mA) at a rate 5 to 10 beats higher than the patient's heart rate. False and true pacing were performed in random sequence, with both patients and investigators having no knowledge of the type of stimulation being administered. RESULTS No control subject had pacing-induced pain; conversely, 8 patients with syndrome X reported angina during atrial pacing (50%, p < 0.01) and 15 during ventricular pacing (94%, p < 0.001). During atrial stimulation, both true and false pacing caused chest pain in a similar proportion of patients (50% vs. 63%, p = 0.61), whereas during ventricular stimulation, true pacing caused chest pain in a higher proportion of patients (94% vs. 50%, p < 0.05). Pain threshold and severity of pain (1 to 10 scale) were similar during true and false atrial pacing, whereas true ventricular pacing resulted in a lower pain threshold (mean +/- SD 3.7 +/- 3.0 vs. 7.9 +/- 2.8 mA, p < 0.001) and a higher level of pain severity (7.3 +/- 2.7 vs. 3.1 +/- 3.5, p < 0.001) than did false pacing. CONCLUSIONS Patients with syndrome X frequently reported chest pain even in the absence of cardiac stimulation. Yet, in addition to this increased tendency to complain, they also exhibited a selective enhancement of ventricular painful sensitivity to electrical stimulation.
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Affiliation(s)
- V Pasceri
- Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Rome, Italy
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Lanza GA, Pasceri V, Colonna G, Cucinelli F, Fortini A, Lanzone A, Crea F, Maseri A. Cardiac autonomic function and sensitivity to pain in postmenopausal women with angina and normal coronary arteries. Am J Cardiol 1997; 79:1174-9. [PMID: 9164880 DOI: 10.1016/s0002-9149(97)00077-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
An increased sensitivity to painful stimuli and an abnormal cardiac autonomic function have previously been reported in patients with angina and angiographically normal coronary arteries, a syndrome that mainly affects postmenopausal women. In this study we compared both general sensitivity to pain, by evaluating time to forearm ischemic pain (FIP) provoked by sphygmomanometer cuff inflation, and cardiac autonomic function, by measuring heart rate variability (HRV), and QT and QT(c) intervals on 24-hour Holter recordings, in 25 postmenopausal women with angina and normal coronary arteries and in 22 healthy postmenopausal women. Compared with controls, patients had a reproducible strikingly lower time to FIP (149 +/- 121 vs 295 +/- 158 seconds, p <0.001), whereas there were no differences between the 2 groups in HRV variables and mean 24-hour QT and QT(c) intervals. HRV indexes, and QT and QT(c) intervals also showed similar circadian patterns. Thus, our data show that postmenopausal women with angina and normal coronary arteries have an enhanced sensitivity to systemic painful stimuli, but no detectable impairment in cardiac autonomic function compared with a well-matched control group of postmenopausal healthy women.
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Affiliation(s)
- G A Lanza
- Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Rome, Italy
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Lenz FA, Dougherty PM, Traill TA. Thalamic mechanisms of chest pain in the absence of cardiac pathology. HEART (BRITISH CARDIAC SOCIETY) 1996; 75:429-30. [PMID: 8665328 PMCID: PMC484332 DOI: 10.1136/hrt.75.5.429] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
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