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Durcan C, Hossain M, Chagnon G, Perić D, Girard E. Mechanical experimentation of the gastrointestinal tract: a systematic review. Biomech Model Mechanobiol 2024; 23:23-59. [PMID: 37935880 PMCID: PMC10901955 DOI: 10.1007/s10237-023-01773-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 09/10/2023] [Indexed: 11/09/2023]
Abstract
The gastrointestinal (GI) organs of the human body are responsible for transporting and extracting nutrients from food and drink, as well as excreting solid waste. Biomechanical experimentation of the GI organs provides insight into the mechanisms involved in their normal physiological functions, as well as understanding of how diseases can cause disruption to these. Additionally, experimental findings form the basis of all finite element (FE) modelling of these organs, which have a wide array of applications within medicine and engineering. This systematic review summarises the experimental studies that are currently in the literature (n = 247) and outlines the areas in which experimentation is lacking, highlighting what is still required in order to more fully understand the mechanical behaviour of the GI organs. These include (i) more human data, allowing for more accurate modelling for applications within medicine, (ii) an increase in time-dependent studies, and (iii) more sophisticated in vivo testing methods which allow for both the layer- and direction-dependent characterisation of the GI organs. The findings of this review can also be used to identify experimental data for the readers' own constitutive or FE modelling as the experimental studies have been grouped in terms of organ (oesophagus, stomach, small intestine, large intestine or rectum), test condition (ex vivo or in vivo), number of directions studied (isotropic or anisotropic), species family (human, porcine, feline etc.), tissue condition (intact wall or layer-dependent) and the type of test performed (biaxial tension, inflation-extension, distension (pressure-diameter), etc.). Furthermore, the studies that investigated the time-dependent (viscoelastic) behaviour of the tissues have been presented.
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Affiliation(s)
- Ciara Durcan
- Zienkiewicz Centre for Modelling, Data and AI, Faculty of Science and Engineering, Swansea University, Swansea, SA1 8EN, UK
- Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France
| | - Mokarram Hossain
- Zienkiewicz Centre for Modelling, Data and AI, Faculty of Science and Engineering, Swansea University, Swansea, SA1 8EN, UK.
| | - Grégory Chagnon
- Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France
| | - Djordje Perić
- Zienkiewicz Centre for Modelling, Data and AI, Faculty of Science and Engineering, Swansea University, Swansea, SA1 8EN, UK
| | - Edouard Girard
- Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000, Grenoble, France
- Laboratoire d'Anatomie des Alpes Françaises, Université Grenoble Alpes, Grenoble, France
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Ofer F, Custon N, Scott S, Abraham K. Functional esophageal chest pain, functional heartburn and reflux hypersensitivity. CLINICAL AND BASIC NEUROGASTROENTEROLOGY AND MOTILITY 2020:247-262. [DOI: 10.1016/b978-0-12-813037-7.00017-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Suciu A, Popa SL, Dumitrascu DL. Upper Gastrointestinal Sensitization And Symptom Generation. J Med Life 2019; 12:316-321. [PMID: 32025247 PMCID: PMC6993284 DOI: 10.25122/jml-2019-0111] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 11/20/2019] [Indexed: 12/29/2022] Open
Abstract
Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders, and their diagnostic criteria are symptom-based, with the absence of anatomical and biochemical abnormalities of the gastrointestinal tract. Chronic visceral symptoms are common both in patients with an identifiable organic disease but also in FGID patients. Patients suffering from upper gastrointestinal functional disorders typically present with various symptoms such as early satiety, postprandial fullness, bloating, nausea, vomiting, and epigastric pain. Considering their increasing prevalence, difficulties in diagnosis, and low quality of life, FGIDs have become an emerging problem in gastroenterology. We aimed to provide an updated summary of pathways involved in visceral sensitization. We examined the recent literature searching for evidence of the most important studies about the mechanisms underlying gastrointestinal symptom generation and sensitization.
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Affiliation(s)
| | - Stefan-Lucian Popa
- Second Medical Department “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Romania
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Gregersen H, Lo KM. What Is the Future of Impedance Planimetry in Gastroenterology? J Neurogastroenterol Motil 2018; 24:166-181. [PMID: 29605974 PMCID: PMC5885717 DOI: 10.5056/jnm18013] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 02/09/2018] [Indexed: 12/13/2022] Open
Abstract
The gastrointestinal (GI) tract is efficient in transporting ingested material to the site of delivery in healthy subjects. A fine balance exists between peristaltic forces, the mixing and delivery of the contents, and sensory signaling. This fine balance is easily disturbed by diseases. It is mandatory to understand the pathophysiology to enhance our understanding of GI disorders. The inaccessibility and complex nervous innervation, geometry and mechanical function of the GI tract make mechanosensory evaluation difficult. Impedance planimetry is a distension technology that assesses luminal geometry, mechanical properties including muscle dynamics, and processing of nociceptive signals from the GI tract. Since standardized models do not exist for GI muscle function in vivo, models, concepts, and terminology must be borrowed from other medical fields such as cardiac mechanophysiology. The review highlights the impedance planimetric technology, muscle dynamics assessment, and 3 applied technologies of impedance planimetry. These technologies are the multimodal probes that assesses sensory function, the functional luminal imaging probe that dynamically measures the geometry of the lumen it distends, and Fecobionics that is a simulated feces providing high-resolution measurements during defecation. The advanced muscle analysis and 3 applied technologies can enhance the quality of future interdisciplinary research for gaining more knowledge about mechanical function, sensory-motor disorders, and symptoms. This is a step in the direction of individualized treatment for GI disorders based on diagnostic subtyping. There seems to be no better alternatives to impedance planimetry, but only the functional luminal imaging probe is currently commercially available. Wider use depends on commercialization of the multimodal probe and Fecobionics.
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Affiliation(s)
- Hans Gregersen
- GIOME, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong.,California Medical Innovations Institute, San Diego, California, USA
| | - Kar Man Lo
- GIOME Doublecove, Wu Kai Sha, New Territories, Hong Kong
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Abstract
The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.
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Malik Z, Bayman L, Valestin J, Rizvi-Toner A, Hashmi S, Schey R. Dronabinol increases pain threshold in patients with functional chest pain: a pilot double-blind placebo-controlled trial. Dis Esophagus 2017; 30:1-8. [PMID: 26822791 DOI: 10.1111/dote.12455] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Noncardiac chest pain is associated with poor quality of life and high care expenditure. The majority of noncardiac chest pain is either gastresophageal reflux disease related or due to esophageal motility disorders, and the rest are considered functional chest pain (FCP) due to central and peripheral hypersensitivity. Current treatment of FCP improves 40-50% of patients. Cannabinoid receptors 1 (CB1) and 2 (CB2) modulate release of neurotransmitters; CB1 is located in the esophageal epithelium and reduces excitatory enteric transmission and potentially could reduce esophageal hypersensitivity. We performed a prospective study to evaluate its effects on pain threshold, frequency, and intensity in FCP. Subjects with FCP received dronabinol (5 mg, twice daily; n = 7; average age, 44 years; mean body mass index, 26.7) or placebo (n = 6; average age, 42 years; mean body mass index, 25.9) for 28 days (4 weeks). Chest pain, general health, and anxiety/depression questionnaires were assessed at baseline and at 4 weeks. Subjects underwent an esophageal balloon distention test prior to treatment and on last day of the study. Dronabinol increased pain thresholds significantly (3.0 vs. 1.0; P = 0.03) and reduced pain intensity and odynophagia compared to placebo (0.18 vs. 0.01 and 0.12 vs. 0.01, respectively, P = 0.04). Depression and anxiety scores did not differ between the groups at baseline or after treatment. No significant adverse effects were observed. In this novel study, dronabinol increased pain threshold and reduced frequency and intensity of pain in FCP. Further, large scale studies are needed to substantiate these findings.
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Affiliation(s)
- Z Malik
- Section of Gastroenterology, Temple University Hospital, Philadelphia, Pennsylvania, USA
| | - L Bayman
- Division of Gastroenterology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
| | - J Valestin
- Division of Gastroenterology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
| | - A Rizvi-Toner
- Division of Gastroenterology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
| | - S Hashmi
- Division of Gastroenterology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
| | - R Schey
- Section of Gastroenterology, Temple University Hospital, Philadelphia, Pennsylvania, USA.,Division of Gastroenterology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
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Min YW, Rhee PL. Esophageal hypersensitivity in noncardiac chest pain. Ann N Y Acad Sci 2016; 1380:27-32. [PMID: 27496289 DOI: 10.1111/nyas.13182] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Revised: 06/13/2016] [Accepted: 06/20/2016] [Indexed: 01/04/2025]
Abstract
Noncardiac chest pain (NCCP) is an often-encountered clinical problem. Although many patients suffer from persistent or recurrent chest pain, treatment remains a challenge owing to its various possible etiologies. Gastroesophageal reflux disease (GERD) is the most common cause of NCCP. In GERD-related NCCP, proton pump inhibitor treatment appears to be effective. However, the pathophysiology remains to be fully elucidated in NCCP patients without GERD. Treatment for non-GERD-related NCCP has been aimed at esophageal motility disorders and visceral hypersensitivity. As there is growing evidence that esophageal visceral hypersensitivity plays a role in NCCP, pain modulators have become the mainstay of therapy in patients with non-GERD-related NCCP. However, there is an unmet need for the treatment of esophageal hypersensitivity in NCCP due to modest evidence for the benefit of pain modulators, including antidepressants, in non-GERD-related NCCP. Recent studies have demonstrated that esophageal mast cell infiltration and impaired mucosal integrity are related to visceral hypersensitivity in patients with NCCP. Thus, esophageal mast cell stabilization and restoration of esophageal mucosal integrity could be considered potential therapeutic targets in selected NCCP patients with hypersensitivity. However, further observations are necessary to shed light on esophageal hypersensitivity in NCCP.
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Affiliation(s)
- Yang Won Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Poong-Lyul Rhee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Ortiz-Garrido O, Ortiz-Olvera NX, González-Martínez M, Morán-Villota S, Vargas-López G, Dehesa-Violante M, Ruiz-de León A. Clinical assessment and health-related quality of life in patients with non-cardiac chest pain. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2015; 80:121-9. [PMID: 26148745 DOI: 10.1016/j.rgmx.2015.03.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Revised: 03/31/2015] [Accepted: 03/31/2015] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Non-cardiac chest pain (NCCP) is mainly related to oesophageal disease, and in spite of being a common condition in Mexico, information regarding it is scarce. AIM To assess the clinical characteristics and health-related quality of life of patients with NCCP of presumed oesophageal origin. MATERIAL AND METHODS Patients with NCCP of presumed oesophageal origin with no previous treatment were included in the study. Associated symptoms were assessed and upper gastrointestinal endoscopy and 24-hour oesophageal pH monitoring were performed to diagnose gastroesophageal reflux disease, while oesophageal manometry was used to determine oesophageal motility disorders. The SF-36 Health-Related Quality of Life (HR-QoL) questionnaire was completed and its results compared to a control group without oesophageal symptoms. RESULTS The study included 33 patients, of which 61% were women, and the mean age was 46.1 (±11.6) years. Causes of NCCP were gastroesophageal reflux disease in 48%, achalasia in 34%, and functional chest pain in 18%. The average progression time for chest pain was 24 (2-240) months, with ≤ 3 events/week in 52% of the patients. The most frequent accompanying symptoms were: regurgitation (81%), dysphagia (72%) and heartburn (66%). Patients with NCCP show deterioration in HR-QoL compared to the control group (P=.01), regardless of chest pain aetiology. The most affected areas were general perception of health, emotional issues, and mental health sub-scale (P>0.05). CONCLUSIONS In our population, patients with NCCP show deterioration in HR-QoL regardless of the aetiology, frequency, and accompanying symptoms.
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Affiliation(s)
- O Ortiz-Garrido
- Departamento de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional SXXI, México, D.F
| | - N X Ortiz-Olvera
- Departamento de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional SXXI, México, D.F..
| | - M González-Martínez
- Laboratorio de motilidad, Servicio de Endoscopia, Hospital de Especialidades, Centro Médico Nacional SXXI, México, D.F
| | - S Morán-Villota
- Laboratorio de Investigación en Gastroenterología, Hospital de Pediatría, Centro Médico Nacional SXXI. México, D.F
| | - G Vargas-López
- Departamento de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional SXXI, México, D.F
| | - M Dehesa-Violante
- Departamento de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional SXXI, México, D.F
| | - A Ruiz-de León
- Servicio de Aparato Digestivo, Hospital Universitario Clínico San Carlos. Madrid, España
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Abstract
Hypnotherapy is an evidence based intervention for the treatment of functional bowel disorders, particularly irritable bowel syndrome. While similar in pathophysiology, less is known about the utility of hypnotherapy in the upper gastrointestinal tract. Esophageal disorders, most of which are functional in nature, cause painful and uncomfortable symptoms that impact patient quality of life and are difficult to treat from a medical perspective. After a thorough medical workup and a failed trial of proton pump inhibitor therapy, options for treatment are significantly limited. While the pathophysiology is likely multifactorial, two critical factors are believed to drive esophageal symptoms--visceral hypersensitivity and symptom hypervigilance. The goal of esophageal directed hypnotherapy is to promote a deep state of relaxation with focused attention allowing the patient to learn to modulate physiological sensations and symptoms that are not easily addressed with conventional medical intervention. Currently, the use of hypnosis is suitable for dysphagia, globus, functional chest pain/non-cardiac chest pain, dyspepsia, and functional heartburn. In this article the authors will provide a rationale for the use of hypnosis in these disorders, presenting the science whenever available, describing their approach with these patients, and sharing a case study representing a successful outcome.
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11
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Ortiz-Garrido O, Ortiz-Olvera N, González-Martínez M, Morán-Villota S, Vargas-López G, Dehesa-Violante M, Ruiz-de León A. Clinical assessment and health-related quality of life in patients with non-cardiac chest pain. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2015. [DOI: 10.1016/j.rgmxen.2015.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
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12
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Ravi K, Katzka DA. Diagnosis and medical management of esophageal dysmotility. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2015. [DOI: 10.1016/j.tgie.2015.03.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Maradey-Romero C, Fass R. Antidepressants for functional esophageal disorders: evidence- or eminence-based medicine? Clin Gastroenterol Hepatol 2015; 13:260-2. [PMID: 25283580 DOI: 10.1016/j.cgh.2014.09.044] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 09/25/2014] [Accepted: 09/26/2014] [Indexed: 02/07/2023]
Affiliation(s)
- Carla Maradey-Romero
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio
| | - Ronnie Fass
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio
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Coss-Adame E, Erdogan A, Rao SSC. Treatment of esophageal (noncardiac) chest pain: an expert review. Clin Gastroenterol Hepatol 2014; 12:1224-45. [PMID: 23994670 PMCID: PMC3938572 DOI: 10.1016/j.cgh.2013.08.036] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2012] [Revised: 08/13/2013] [Accepted: 08/19/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Chest pain is a common and frightening symptom. Once cardiac disease has been excluded, an esophageal source is most likely. Pathophysiologically, gastroesophageal reflux disease, esophageal dysmotility, esophageal hypersensitivity, and anxiety disorders have been implicated. However, treatment remains a challenge. Here we examined the efficacy and safety of various commonly used modalities for treatment of esophageal (noncardiac) chest pain (ECP) and provided evidence-based recommendations. METHODS We reviewed the English language literature for drug trials evaluating treatment of ECP in PubMed, Cochrane, and MEDLINE databases from 1968-2012. Standard forms were used to abstract data regarding study design, duration, outcome measures and adverse events, and study quality. RESULTS Thirty-five studies comprising various treatments were included and grouped under 5 broad categories. Patient inclusion criteria were extremely variable, and studies were generally small with methodological concerns. There was good evidence to support the use of omeprazole and fair evidence for lansoprazole, rabeprazole, theophylline, sertraline, trazodone, venlafaxine, imipramine, and cognitive behavioral therapy. There was poor evidence for nifedipine, diltiazem, paroxetine, biofeedback therapy, ranitidine, nitrates, botulinum toxin, esophageal myotomy, and hypnotherapy. CONCLUSIONS Ideally, treatment of ECP should be aimed at correcting the underlying mechanism(s) and relieving symptoms. Proton pump inhibitors, antidepressants, theophylline, and cognitive behavioral therapy appear to be useful for the treatment of ECP. However, there is urgent and unmet need for effective treatments and for rigorous, randomized controlled trials.
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Affiliation(s)
- Enrique Coss-Adame
- Section of Gastroenterology and Hepatology, Georgia Regents University, Augusta, Georgia
| | - Askin Erdogan
- Section of Gastroenterology and Hepatology, Georgia Regents University, Augusta, Georgia
| | - Satish S C Rao
- Section of Gastroenterology and Hepatology, Georgia Regents University, Augusta, Georgia.
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Gastroesophageal reflux symptoms not responding to proton pump inhibitor: GERD, NERD, NARD, esophageal hypersensitivity or dyspepsia? Can J Gastroenterol Hepatol 2014; 28:335-41. [PMID: 24719900 PMCID: PMC4072238 DOI: 10.1155/2014/904707] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Gastroesophageal reflux (GER) is a common gastrointestinal process that can generate symptoms of heartburn and chest pain. Proton pump inhibitors (PPIs) are the gold standard for the treatment of GER; however, a substantial group of GER patients fail to respond to PPIs. In the past, it was believed that acid reflux into the esophagus causes all, or at least the majority, of symptoms attributed to GER, with both erosive esophagitis and nonerosive outcomes. However, with modern testing techniques it has been shown that, in addition to acid reflux, the reflux of nonacid gastric and duodenal contents into the esophagus may also induce GER symptoms. It remains unknown how weakly acidic or alkaline refluxate with a pH similar to a normal diet induces GER symptoms. Esophageal hypersensitivity or functional dyspepsia with superimposed heartburn may be other mechanisms of symptom generation, often completely unrelated to GER. Detailed studies investigating the pathophysiology of esophageal hypersensitivity are not conclusive, and definitions of the various disease states may overlap and are often confusing. The authors aim to clarify the pathophysiology, definition, diagnostic techniques and medical treatment of patients with heartburn symptoms who fail PPI therapy.
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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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Farmer AD, Coen SJ, Kano M, Naqvi H, Paine PA, Scott SM, Furlong PL, Lightman SL, Knowles CH, Aziz Q. Psychophysiological responses to visceral and somatic pain in functional chest pain identify clinically relevant pain clusters. Neurogastroenterol Motil 2014; 26:139-48. [PMID: 24134072 DOI: 10.1111/nmo.12245] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2013] [Accepted: 09/15/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND Despite chronic pain being a feature of functional chest pain (FCP) its experience is variable. The factors responsible for this variability remain unresolved. We aimed to address these knowledge gaps, hypothesizing that the psychophysiological profiles of FCP patients will be distinct from healthy subjects. METHODS 20 Rome III defined FCP patients (nine males, mean age 38.7 years, range 28-59 years) and 20 healthy age-, sex-, and ethnicity-matched controls (nine males, mean 38.2 years, range 24-49) had anxiety, depression, and personality traits measured. Subjects had sympathetic and parasympathetic nervous system parameters measured at baseline and continuously thereafter. Subjects received standardized somatic (nail bed pressure) and visceral (esophageal balloon distension) stimuli to pain tolerance. Venous blood was sampled for cortisol at baseline, post somatic pain and post visceral pain. KEY RESULTS Patients had higher neuroticism, state and trait anxiety, and depression scores but lower extroversion scores vs controls (all p < 0.005). Patients tolerated less somatic (p < 0.0001) and visceral stimulus (p = 0.009) and had a higher cortisol at baseline, and following pain (all p < 0.001). At baseline, patients had a higher sympathetic tone (p = 0.04), whereas in response to pain they increased their parasympathetic tone (p ≤ 0.008). The amalgamating the data, we identified two psychophysiologically distinct 'pain clusters'. Patients were overrepresented in the cluster characterized by high neuroticism, trait anxiety, baseline cortisol, pain hypersensitivity, and parasympathetic response to pain (all p < 0.03). CONCLUSIONS & INFERENCES In future, such delineations in FCP populations may facilitate individualization of treatment based on psychophysiological profiling.
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Affiliation(s)
- A D Farmer
- Centre for Digestive Diseases, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK
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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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Park SW, Lee H, Lee HJ, Park JC, Shin SK, Lee SK, Lee YC, Kim JE. Low-dose amitriptyline combined with proton pump inhibitor for functional chest pain. World J Gastroenterol 2013; 19:4958-4965. [PMID: 23946601 PMCID: PMC3740426 DOI: 10.3748/wjg.v19.i30.4958] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2013] [Accepted: 07/01/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the efficacy of amitriptyline with proton pump inhibitor (PPI) for the treatment of functional chest pain (FCP).
METHODS: This was a randomized, open-label trial investigating the addition of low dose amitriptyline (10 mg at bedtime) to a conventional dose of rabeprazole (20 mg/d) (group A, n = 20) vs a double-dose of rabeprazole (20 mg twice daily) (group B, n = 20) for patients with FCP whose symptoms were refractory to PPI. The primary efficacy endpoints were assessed by global symptom score assessment and the total number of individuals with > 50% improvement in their symptom score.
RESULTS: The between-group difference in global symptom scores was statistically significant during the last week of treatment (overall mean difference; 3.75 ± 0.31 vs 4.35 ± 0.29, the between-group difference; P < 0.001). Furthermore, 70.6% of patients in group A had their symptoms improve by > 50%, whereas only 26.3% of patients in group B had a similar treatment response (70.6% vs 26.3%, P = 0.008). Specifically, patients in group A had a significantly greater improvement in the domains of body pain and general health perception than did patients in group B (52.37 ± 17.00 vs 41.32 ± 12.34, P = 0.031 and 47.95 ± 18.58 vs 31.84 ± 16.84, P = 0.01, respectively).
CONCLUSION: Adding amitriptyline to a PPI was more effective than a double-dose of PPI in patients with FCP refractory to a conventional dose of PPI.
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Kim JH, Choi YS, Kim JJ, Rhee JC, Rhee PL. Characteristics of esophageal proper muscle in patients with non-cardiac chest pain using high-frequency intraluminal ultrasound. J Gastroenterol Hepatol 2013; 28:488-493. [PMID: 22989117 DOI: 10.1111/j.1440-1746.2012.07263.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/31/2012] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM It is unclear which mechanisms play a predominant role in the pathogenesis of esophageal non-cardiac chest pain (NCCP). We aimed to examine the features of esophageal proper muscle and esophageal contractility using a high-frequency intraluminal ultrasound (HFIUS) in patients with NCCP. METHODS A total of 68 patients with NCCP were classified into two groups according to the results of typical reflux symptoms and/or esophagogastroduodenoscopy and/or 24-h esophageal pH monitoring: gastroesophageal reflux disease (GERD)-positive NCCP (n = 34) and GERD-negative NCCP groups (n = 34). Additionally 16 asymptomatic healthy subjects were included as controls. Using HFIUS, we analyzed the esophageal proper muscle thickness and cross-sectional area (CSA) at 3 cm above lower esophageal sphincter (LES) and 9 cm above LES during baseline rest and peak contraction periods among the control, GERD-positive NCCP and GERD-negative NCCP groups, and examined the completeness of three phases of esophageal action during five wet swallows in the three groups. RESULTS The muscle thickness and CSA tended to be larger in GERD-negative NCCP than in GERD-positive NCCP and in control groups at esophageal body during both periods. All of the controls and patients with GERD-positive NCCP presented the complete peristaltic type. Whereas, 11 of 34 patients with GERD-negative NCCP presented the incomplete peristaltic type. CONCLUSIONS Using HFIUS, patients with GERD-negative NCCP had increased muscle thickness and CSA. Some GERD-negative NCCP had the incomplete peristaltic type.
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Affiliation(s)
- Jeong Hwan Kim
- Department of Internal Medicine, Digestive Disease Center, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
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Shaker A, Gyawali CP. Esophageal Chest Pain. CHEST PAIN WITH NORMAL CORONARY ARTERIES 2013:23-34. [DOI: 10.1007/978-1-4471-4838-8_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Lee H, Park JC, Shin SK, Lee SK, Lee YC. Segmental changes in smooth muscle contraction as a predictive factor of the response to high-dose proton pump inhibitor treatment in patients with functional chest pain. J Gastroenterol Hepatol 2012; 27:1192-9. [PMID: 22413883 DOI: 10.1111/j.1440-1746.2012.07110.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS High-dose proton pump inhibitor (PPI) treatment leads to relatively little symptomatic improvement in patients with functional chest pain (FCP). This study was to evaluate the use of smooth muscle segmental changes in esophageal contraction as measured by topographical plots of high resolution manometry (HRM) as predictive factors of the response to high-dose PPI treatment in FCP patients. METHODS Thirty patients diagnosed with FCP were treated with rabeprazole 20 mg twice daily for 2 weeks and classified as positive and negative responders based on symptom intensity score. HRM topographical plots were analyzed for segment lengths, maximal wave amplitudes, and pressure volumes of the proximal and distal smooth muscle segments. RESULTS A positive response was observed in 23.3% of the patients. While the pressure volume of the proximal segment was significantly higher in the positive responders than the negative responders (900.4 ± 91.5 mm Hg/cm per s vs. 780.5 ± 133.3 mm Hg/cm per s, P = 0.017), the pressure volume of the distal segment was significantly lower in the positive responders (1914.0 ± 159.8 mm Hg/cm per s vs. 2140.5 ± 276.2 mm Hg/cm per s, P = 0.014). A prominent shifting in pressure volume to the distal segment was observed in the negative responders compared with the positive responders (segmental ratio of pressure volume (SRPV): 2.9 ± 0.5 vs. 2.1 ± 0.1, P < 0.001), and 2.39 was found to be the SRPV that best differentiated positive and negative responders. CONCLUSIONS A low SRPV was associated with a positive response to high-dose PPI treatment in patients with FCP.
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Affiliation(s)
- Hyuk Lee
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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Clarke JO, Pandolfino JE. Esophageal motor disorders: how to bridge the gap between advanced diagnostic tools and paucity of therapeutic modalities? J Clin Gastroenterol 2012; 46:442-8. [PMID: 22688141 DOI: 10.1097/mcg.0b013e31823d30c1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
High-resolution manometry has added significantly to our current understanding of esophageal motor function by providing improved detail and a data analysis paradigm that is more akin to an imaging format. Esophageal pressure topography provides a seamless dynamic representation of the pressure profile through the entire esophagus and thus, is able to eliminate movement artifact and also assess intrabolus pressure patterns as a surrogate for bolus transit mechanics. This has led to improved identification of anatomic landmarks and measurement of important physiological parameters (esophagogastric junction relaxation, distal latency, and contractile integrity). This research has bridged the gap into clinical practice by defining physiologically relevant phenotypes that may have prognostic significance and improve treatment decisions in achalasia, spasm, and hypercontractile disorders. However, more work is needed in determining the etiology of symptom generation in the context of normal or trivial motor dysfunction. This research will require new techniques to assess visceral hypersensitivity and alterations in central modulation of pain and discomfort.
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Affiliation(s)
- John O Clarke
- Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Fass R, Herschcovici T. Non‐Cardiac Chest Pain. THE ESOPHAGUS 2012:14-41. [DOI: 10.1002/9781444346220.ch2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Husser D, Bollmann A, Kühne C, Molling J, Klein HU. Evaluation of noncardiac chest pain: diagnostic approach, coping strategies and quality of life. Eur J Pain 2012; 10:51-5. [PMID: 16291298 DOI: 10.1016/j.ejpain.2005.01.011] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2004] [Accepted: 01/20/2005] [Indexed: 11/20/2022]
Abstract
BACKGROUND Approximately 30% of coronary angiograms are negative for significant coronary artery disease and patients are classified as having noncardiac chest pain (NCCP). So far, no systematic diagnostic approach to patients with NCCP investigating for possible esophageal, psychiatric and musculoskeletal abnormalities exists. Furthermore, coping strategies and quality of life are poorly characterized in NCCP patients. METHODS AND RESULTS A simple diagnostic approach was applied to 37 consecutive patients (21 female, age 61+/-12 years) with angina-like chest pain and normal coronary angiograms. Twenty-one patients were found to suffer from psychiatric disorders (combined anxiety (A) and depression (D): n = 10, D: n = 5, panic disorder (P): n = 3, somatization (S): n = 3) based on their Symptom Check List 90 scores and according to DSM IV-R criteria. Sixteen patients had an improvement of their chest pain after oral esomeprazole (40 mg for 7 days) and were therefore diagnosed with gastroesophageal reflux disease (GERD). Musculoskeletal abnormalities including chostochondritis (n = 4), thoracic spondylodynia (n = 1), and fibromyalgia (n = 1) were found in six patients. Multiple diagnoses were confirmed in six patients with GERD (additional D n = 3, additional musculoskeletal disorders n = 3). Patients with psychiatric disorders showed a diminished quality of life (MOS-SF 36), more frequent chest pain, less treatment satisfaction (Seattle Angina Questionnaire) and more rumination (Trier Coping Scales) compared to GERD patients. CONCLUSIONS Immediate combined psychiatric and orthopedic evaluation as well as esomeprazole administration following exclusion of coronary artery disease may confirm the causes of noncardiac chest pain. Identification of psychiatric disorders seems especially warranted since these patients experience a reduced quality of life and exhibit pathologic coping strategies.
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Affiliation(s)
- Daniela Husser
- Department of Cardiology, University Hospital Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany
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Remes-Troche JM, Attaluri A, Chahal P, Rao SS. Barostat or dynamic balloon distention test: which technique is best suited for esophageal sensory testing? Dis Esophagus 2012; 25:584-9. [PMID: 22168228 PMCID: PMC4038032 DOI: 10.1111/j.1442-2050.2011.01294.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Esophageal sensation is commonly assessed by barostat-assisted balloon distension (BBD) or dynamic balloon distension (DBD) technique, but their relative merits are unknown. Our aim was to compare the usefulness and tolerability of both techniques. Sixteen healthy volunteers (male/female = 6/10) randomly underwent graded esophageal balloon distensions, using either BBD (n= 8) or DBD (n= 8). BBD was performed by placing a 5-cm long highly compliant balloon attached to a barostat, and DBD by placing a 5-cm long balloon attached to a leveling container. Intermittent phasic balloon distensions were performed in increments of 6 mm Hg. Sensory thresholds and biomechanical properties were assessed and compared. Sensory thresholds for first perception (mean ± standard deviation; 21 ± 6 vs. 21.2 ± 5, mm Hg, P= 0.9), discomfort (38 ± 8 vs. 35 ± 9, P= 0.5), and pain (44 ± 4 vs. 45 ± 3, P= 0.7) were similar with BBD and DBD techniques. However, more subjects tolerated DBD (7/8, 88%) when compared with BBD (4/8, 50%). Forceful expulsion of balloon into stomach (n= 4), pulling around the mouth (n= 4), chest discomfort (n= 2) and retching (n= 2) were overlapping reasons for intolerance with BBD. Esophageal wall distensibility was similar with both techniques. Both techniques provided comparable data on biomechanical properties. However, DBD was better tolerated than BBD for evaluation of esophageal sensation. Hence, we recommend DBD for performing esophageal balloon distension test.
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Affiliation(s)
- Jose M. Remes-Troche
- Division of Neurogastroenterology and Motility, Department of Internal Medicine and Clinical Translational Research Center, University of Iowa Carver College of Medicine, Iowa City, Iowa,Digestive Physiology and Motility Department, Medical-Biological Research Institute, University of Veracruz, Mexico
| | - Ashok Attaluri
- Division of Neurogastroenterology and Motility, Department of Internal Medicine and Clinical Translational Research Center, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | - Premjit Chahal
- Division of Neurogastroenterology and Motility, Department of Internal Medicine and Clinical Translational Research Center, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | - Satish S.C. Rao
- Division of Neurogastroenterology and Motility, Department of Internal Medicine and Clinical Translational Research Center, University of Iowa Carver College of Medicine, Iowa City, Iowa
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The pain system in oesophageal disorders: mechanisms, clinical characteristics, and treatment. Gastroenterol Res Pract 2011; 2011:910420. [PMID: 21826137 PMCID: PMC3150142 DOI: 10.1155/2011/910420] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2011] [Accepted: 05/23/2011] [Indexed: 12/14/2022] Open
Abstract
Pain is common in gastroenterology. This review aims at giving an overview of pain mechanisms, clinical features, and treatment options in oesophageal disorders. The oesophagus has sensory receptors specific for different stimuli. Painful stimuli are encoded by nociceptors and communicated via afferent nerves to the central nervous system. The pain stimulus is further processed and modulated in specific pain centres in the brain, which may undergo plastic alterations. Hence, tissue inflammation and long-term exposure to pain can cause sensitisation and hypersensitivity. Oesophageal sensitivity can be evaluated ,for example, with the oesophageal multimodal probe. Treatment should target the cause of the patient's symptoms. In gastro-oesophageal reflux diseases, proton pump inhibitors are the primary treatment option, surgery being reserved for patients with severe disease resistant to drug therapy. Functional oesophageal disorders are treated with analgesics, antidepressants, and psychological therapy. Lifestyle changes are another option with less documentation.
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Soto-Pérez JC, Sobrino-Cossío S, Higgins PB, Comuzzie AG, Vargas Romero JA, Reding-Bernal A, López-Alvarenga JC. Distal esophageal hypercontractility is related to abnormal acid exposure. Arch Med Res 2011; 42:104-9. [PMID: 21565622 DOI: 10.1016/j.arcmed.2011.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2010] [Accepted: 01/26/2011] [Indexed: 11/26/2022]
Abstract
BACKGROUND AND AIMS Nutcracker esophagus (NE) is a frequent primary motility disorder of the distal esophagus, and the relationship with acid exposure remains controversial. We studied simultaneous distal esophageal hypercontractility (EH) using two sensors at 8 and 3 cm above the lower sphincter (LES) and abnormal exposure to acid (pH DeMeester score). METHODS From 400 screened patients with chest pain and heartburn, 54 (age 44.5 ± 8.8 years and 74% females) had abnormal manometry and underwent acid exposure measurement. Frequencies of the EH disorder were classic NE (EH(3 cm)) found in 29 (40.8%) patients, diffuse (EH(3,8 cm)) in 30 patients (42.3%), and upper segmental (EH(8 cm)) in 12 patients (16.9%). RESULTS We found a positive correlation among age with high amplitude in EH(3 cm) and EH(3,8 cm). DeMeester's score (DMS) had the lowest value for EH(3,8 cm) (2.58 ± 0.23) compared with EH(8 cm) (3.78 ± 0.3, p <0.003) and EH(3 cm) (3.12 ± 0.2, p <0.06). Surface response for joint effect of age and DMS on amplitude at EH(3 cm) confirmed the highest amplitude was for older age and lower DMS. CONCLUSIONS EH(3 cm) and EH(3,8 cm) were common for esophageal motility and were inversely associated with DMS. Meanwhile, acid exposure was higher in younger patients and hypercontractility was more frequent in older subjects. The former group may benefit more from proton pump inhibitors and the latter from visceral analgesics or possibly both.
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Affiliation(s)
- Julio César Soto-Pérez
- Clínica de Fisiología Digestiva del Hospital Metropolitano y Hospital de Alta Especialidad PEMEX SUR, Mexico, D.F., Mexico
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Fass R, Achem SR. Noncardiac chest pain: epidemiology, natural course and pathogenesis. J Neurogastroenterol Motil 2011; 17:110-23. [PMID: 21602987 PMCID: PMC3093002 DOI: 10.5056/jnm.2011.17.2.110] [Citation(s) in RCA: 128] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2011] [Revised: 03/17/2011] [Accepted: 03/28/2011] [Indexed: 12/24/2022] Open
Abstract
Noncardiac chest pain is defined as recurrent chest pain that is indistinguishable from ischemic heart pain after a reasonable workup has excluded a cardiac cause. Noncardiac chest pain is a prevalent disorder resulting in high healthcare utilization and significant work absenteeism. However, despite its chronic nature, noncardiac chest pain has no impact on patients' mortality. The main underlying mechanisms include gastroesophageal reflux, esophageal dysmotility and esophageal hypersensitivity. Gastroesophageal reflux disease is likely the most common cause of noncardiac chest pain. Esophageal dysmotility affects only the minority of noncardiac chest pain patients. Esophageal hypersensitivity may be present in non-GERD-related noncardiac chest pain patients regardless if esophageal dysmotility is present or absent. Psychological co-morbidities such as panic disorder, anxiety, and depression are also common in noncardiac chest pain patients and often modulate patients' perception of disease severity.
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Affiliation(s)
- Ronnie Fass
- Section of Gastroenterology, Department of Medicine, Southern Arizona VA Health Care System, Tucson, Arizona, USA.
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The hypersensitive esophagus: pathophysiology, evaluation, and treatment options. Curr Gastroenterol Rep 2011; 12:417-26. [PMID: 20669058 DOI: 10.1007/s11894-010-0122-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Visceral hypersensitivity plays a key role in the pathogenesis of esophageal functional disorders such as functional heartburn and chest pain of presumed esophageal origin (noncardiac chest pain). About 80% of patients with unexplained noncardiac chest pain exhibit lower esophageal sensory thresholds when compared to controls during esophageal sensory testing (ie, esophageal barostat, impedance planimetry). Such information has led to prescription of peripherally and/or centrally acting therapies for the management of these patients. This review summarizes and highlights recent and significant findings regarding the pathophysiology, evaluation, and treatment of the hypersensitive esophagus, a central factor in functional esophageal disorders.
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Lee H, Kim JH, Min BH, Lee JH, Son HJ, Kim JJ, Rhee JC, Suh YJ, Kim S, Rhee PL. Efficacy of venlafaxine for symptomatic relief in young adult patients with functional chest pain: a randomized, double-blind, placebo-controlled, crossover trial. Am J Gastroenterol 2010; 105:1504-12. [PMID: 20332772 DOI: 10.1038/ajg.2010.82] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Esophageal hypersensitivity is currently believed to have a crucial role in the pathogenesis of functional chest pain (FCP). The aim of this study was to evaluate the clinical efficacy of venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), for FCP in young adult patients. METHODS Patients diagnosed with FCP were randomized to either an extended-release formulation of venlafaxine (75 mg hora somni) or a placebo for 4 weeks. After a washout period of 2 weeks, patients crossed over to the other arm of the study. The primary efficacy variable was the number of patients with >50% improvement in symptom scores. The secondary efficacy variables were (i) the symptom intensity score during each week, (ii) quality of life (QOL), (iii) the Beck Depression Inventory (BDI) score, and (iv) side effects. RESULTS A total of 43 patients (37 men, mean age 23.5 + or - 1.9 years) completed the study. A positive response was observed in 52.0% of patients during venlafaxine treatment; 4.0% had a positive response with placebo treatment as assessed by the intention-to-treat analysis (venlafaxine vs. placebo: odds ratio 26.0; 95% confidence interval 5.7-118.8; P<0.001). Results of Short-Form 36 (SF-36) indicated that patients who received venlafaxine treatment had a significantly greater improvement in body pain and emotional role compared with those who received placebo treatment (P=0.002 and P=0.002, respectively). No significant change was noted in the depression score after venalafaxine or placebo treatment. One patient withdrew from the study because of sleep disturbance and loss of appetite while receiving venlafaxine. CONCLUSIONS Venlafaxine, an SNRI antidepressant, significantly improved symptoms in young adult patients with FCP.
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Affiliation(s)
- Hyuk Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Nasr I, Attaluri A, Hashmi S, Gregersen H, Rao SSC. Investigation of esophageal sensation and biomechanical properties in functional chest pain. Neurogastroenterol Motil 2010; 22:520-6, e116. [PMID: 20067548 PMCID: PMC2949059 DOI: 10.1111/j.1365-2982.2009.01451.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND There is limited and conflicting data regarding the role of esophageal hypersensitivity in the pathogenesis of functional chest pain (FCP). We examined esophageal sensori-motor properties, mechanics, and symptoms in subjects with FCP. METHODS Esophageal balloon distension test was performed using impedance planimetry in 189 (m/f = 57/132) consecutive subjects with non-cardiac, non-reflux chest pain, and 36 (m/f = 16/20) healthy controls. The biomechanical and sensory properties of subjects with and without esophageal hypersensitivity were compared with controls. The frequency, intensity, and duration of chest pain were assessed. KEY RESULTS One hundred and forty-three (75%) subjects had esophageal hypersensitivity and 46 (25%) had normal sensitivity. Typical chest pain was reproduced in 105/143 (74%) subjects. Subjects with hypersensitivity demonstrated larger cross-sectional area (P < 0.001), decreased esophageal wall strain (P < 0.001) and distensibility (P < 0.001), and lower thresholds for perception (P < 0.01), discomfort (P < 0.01), and pain (P < 0.01) compared to those without hypersensitivity or healthy controls. Chest pain scores (mean +/- SD) for frequency, intensity and duration were 2.5 +/- 0.3, 2.2 +/- 0.2, and 2.2 +/- 0.2, respectively, and were similar between the two patient groups. CONCLUSIONS & INFERENCES Seventy-five per cent of subjects with FCP demonstrate esophageal hypersensitivity. Visceral hyperalgesia and sensori-motor dysfunction of the esophagus play a key role in the pathogenesis of chest pain.
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Affiliation(s)
- I Nasr
- Department of Internal Medicine, University of Iowa Carver College of medicine, Iowa City, IA, USA
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Domingues GRDS, Moraes-Filho JPP. [Non-cardiac chest pain]. ARQUIVOS DE GASTROENTEROLOGIA 2009; 46:233-40. [PMID: 19918693 DOI: 10.1590/s0004-28032009000300018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/22/2009] [Accepted: 04/15/2009] [Indexed: 11/21/2022]
Abstract
CONTEXT Non-cardiac chest pain or functional chest pain is a syndrome with high prevalence in occidental world. Findings on 15%-30% of coronary angiograms performed in patients with chest pain are normal. Causes significant impact in quality of life of patients and is associated with increased use of the health care facilities. DATA SOURCES To this review the following data base were accessed: Medline, the Cochrane Library, LILACS. The limit was the last 5 years publications and were selected relevant original articles, reviews, consensus, guidelines and meta-analysis. RESULTS Forty-four papers were selected, 28 original articles, 12 reviews, 2 guidelines, 1 consensus and 1 meta-analysis. CONCLUSIONS Exclusion of cardiac disease is of crucial importance. On the other hand non-cardiac chest pain could be related to gastrointestinal, muscular and respiratory causes and/or psychological disturbances. Treatment aims to attack mechanism generator in order to relieve or to eliminate symptoms. Drugs are the cornerstone of treatment, exception to achalasia patients because those have better response to dilation of the esophagus or surgery, and to those who need intensive psychological therapy. The most important drugs used are proton pump inhibitors and tricyclic antidepressants, the latter, to modulate central signal process (visceral hypersensitivity) and autonomic response. Recently, new diagnostic facilities, and also therapeutic modalities, such as esophageal botulin toxin injection and hypnosis are under investigations. In the near future, maybe some of them would take a place in the therapeutic scenario of these patients.
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Qin C, Farber JP, Foreman RD. Intraesophageal chemicals enhance responsiveness of upper thoracic spinal neurons to mechanical stimulation of esophagus in rats. Am J Physiol Gastrointest Liver Physiol 2008; 294:G708-16. [PMID: 18187515 DOI: 10.1152/ajpgi.00477.2007] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Esophageal hypersensitivity is one of the most common causes of noncardiac chest pain in patients. In this study, we investigated whether exposure of the esophagus to acid and other chemical irritants affected activity of thoracic spinal neurons responding to esophageal distension (ED) in rats. Extracellular potentials of single thoracic (T3) spinal neurons were recorded in pentobarbital sodium-anesthetized, -paralyzed, and -ventilated male rats. ED (0.2 or 0.4 ml, 20 s) was produced by water inflation of a latex balloon placed orally into the middle thoracic region of the esophagus. The chemicals were administered via a tube that was passed through the stomach and placed in the thoracic esophagus. To irritate the esophagus, 0.2 ml of HCl (0.01 N), bradykinin (10 microg/ml), or capsaicin (10 microg/ml) were injected for 1-2 min. Only neurons excited by ED were included in this study. Results showed that intraesophageal instillation of HCl, bradykinin, and capsaicin increased activity in 3/20 (15%), 7/25 (28%), and 9/20 (45%) neurons but enhanced excitatory responses to ED in 9/17 (53%), 8/15 (53%), and 7/11 (64%) of the remaining spinal neurons, respectively. Furthermore, intraesophageal chemicals were more likely to enhance the responsiveness of low-threshold neurons than high-threshold neurons to the esophageal mechanical stimulus. Normal saline (pH 7.4, 0.2 ml) or vehicle instilled in the esophagus did not significantly affect activity or ED responses of neurons. We conclude that enhanced responses of thoracic spinal neurons to ED by the chemically challenged esophagus may provide a possible pathophysiological basis for visceral hypersensitivity in patients with gastroesophageal reflux and/or esophagitis.
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Affiliation(s)
- Chao Qin
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA.
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Cheung TK, Lim PWY, Wong BCY. Noncardiac chest pain--an Asia-Pacific survey on the views of primary care physicians. Dig Dis Sci 2007; 52:3043-8. [PMID: 17436083 DOI: 10.1007/s10620-007-9764-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2006] [Accepted: 01/03/2007] [Indexed: 02/08/2023]
Abstract
Noncardiac chest pain (NCCP) is common and has a significant impact on health care. Primary care physicians (PCPs)' attitudes, clinical approach, preference of diagnostic tests, referral patterns, and comfort in managing patients with NCCP in the Asia-Pacific region are not known. Consequently, we performed this survey in the Asia-Pacific region. The self-completed questionnaire was sent to PCPs in the Asia-Pacific region. A 28-item questionnaire contained questions on demographic information, characteristics of practice, preferences of diagnostic tests, referral patterns, treatment plans, and opinion on Helicobacter pylori and NCCP. A total of 108 (74%) PCPs returned the questionnaire. A mean of 18% of the patients were diagnosed with NCCP by PCPs in the past 6 months. Ninety-four percent of PCPs had treated NCCP patients in the last 6 months. Only 38% of the PCPs were comfortable in diagnosing NCCP but 85.2% believed that they should manage NCCP patients. PCPs in Malaysia and Philippines were more likely to refer patients to subspecialists. Fifty-seven and four-tenths percent of PCPs believed that H. pylori infection plays a role in the development of NCCP. The study demonstrates clearly that the understanding, diagnostic strategies, and treatment strategies of NCCP in the Asia-Pacific region are suboptimal and thus highlights the importance of educational and training programs tailored for PCPs in NCCP.
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Affiliation(s)
- Ting Kin Cheung
- Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong
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Massey BT. Esophageal motor and sensory disorders: presentation, evaluation, and treatment. Gastroenterol Clin North Am 2007; 36:553-75, viii. [PMID: 17950438 DOI: 10.1016/j.gtc.2007.07.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Esophageal motor and sensory disorders are relatively rare conditions in the general population and afflicted patients are often initially misdiagnosed as having gastroesophageal reflux disease. Tests for these disorders have imperfect gold standards and are adjuncts to sound diagnostic reasoning. Treatments are palliative and have not been rigorously evaluated for some disorders. Symptoms and complications from disease progression and relapse are common, so that patients need continued follow-up.
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Affiliation(s)
- Benson T Massey
- GI Manometry Laboratory, Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA.
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Abstract
Motor abnormalities of the oesophagus are characterised by a chronic impairment of the neuromuscular structures that co-ordinate oesophageal function. The best-defined entity is achalasia, which is discussed in a separate chapter. Other motor disorders with clinical relevance include diffuse oesophageal spasm, oesophageal dysmotility associated with scleroderma, and ineffective oesophageal motility. These non-achalasic motor disorders have variable prevalence but they could be associated with invalidating symptoms such as dysphagia, chest pain and gastro-oesophageal reflux disease. New oesophageal diagnostic techniques, including high-resolution manometry, high-frequency intraluminal ultrasound and intraluminal impedance, allow (1) better definition of peristalsis and sphincter function, (2) assessment of changes in oesophageal wall thickness, and (3) evaluation of pressure gradients within the oesophagus and across the sphincters that can produce normal or abnormal patterns of bolus transport. This chapter discusses recent advances in physiology, pathophysiology, diagnosis and treatment of non-achalasic oesophageal motor disorders.
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Affiliation(s)
- Daniel Sifrim
- Centre for Gastroenterological Research, Catholic University of Leuven, Faculty of Medicine, Belgium.
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Rao SSC, Mudipalli RS, Remes-Troche JM, Utech CL, Zimmerman B. Theophylline improves esophageal chest pain--a randomized, placebo-controlled study. Am J Gastroenterol 2007; 102:930-8. [PMID: 17313494 DOI: 10.1111/j.1572-0241.2007.01112.x] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIM The treatment of esophageal (noncardiac) chest pain is unsatisfactory and there is no approved therapy. A previous uncontrolled study suggested that theophylline may be useful. Our aims were to investigate the effects of theophylline on esophageal sensorimotor function and chest pain. METHODS In a double-blind study, sensory and biomechanical properties of the esophagus were assessed using impedance planimetry in 16 patients with esophageal hypersensitivity, after intravenous theophylline or placebo. In a second, randomized 4-wk crossover study, oral theophylline and placebo were administered to 24 patients with esophageal hypersensitivity. Frequency, intensity, and duration of chest pain episodes were evaluated. RESULTS After IV theophylline, chest pain thresholds (P=0.027) and esophageal cross-sectional area (P=0.03) increased and the esophageal wall became more distensible (P=0.04) compared with placebo. After oral theophylline, the number of painful days (P=0.03) and chest pain episodes (P=0.025), pain duration (P=0.002), and its severity (P=0.031) decreased. Overall symptoms improved in 58% on theophylline and 6% on placebo (P<0.02). There was no order effect. CONCLUSIONS Theophylline relaxed the esophageal wall, decreased hypersensitivity, and improved chest pain. Theophylline is effective in the treatment of functional chest pain.
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Affiliation(s)
- Satish S C Rao
- Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA
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Mudipalli RS, Remes-Troche JM, Andersen L, Rao SSC. Functional chest pain: esophageal or overlapping functional disorder. J Clin Gastroenterol 2007; 41:264-9. [PMID: 17426464 DOI: 10.1097/01.mcg.0000225521.36160.1b] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Whether patients with functional chest pain have an esophageal or overlapping functional disorder of the gut is unclear. We investigated the prevalence of functional gastrointestinal disorders in patients with functional chest pain. METHODS One hundred patients with functional chest pain and normal cardiac, endoscopic, and manometric studies were evaluated for esophageal hypersensitivity with a balloon distension test. Subsequently, a modified Rome II functional bowel disorder questionnaire was mailed to these subjects. Prevalence of irritable bowel syndrome (IBS) and other functional disorder were determined using the Rome II criteria. In addition, we assessed the prevalence of chest pain in 81 patients with functional constipation. RESULTS There were 69 responders (54 women); 2 were excluded. Fifty-five patients (82%) fulfilled criteria for other functional disorders besides chest pain. Although there was an overlap, IBS (27%) and abdominal bloating (22%) were most common; dyspepsia (7%), dysphagia (7%), nonspecific bowel disorder (7%), constipation (4%), abdominal pain (3%), and diarrhea (1%) were less common. Among responders, 52 (78%) had esophageal hypersensitivity and 15 (22%) had normosensitivity, with similar prevalence of functional disorders. Thirty-two (39%) of the subjects with functional constipation reported chest pain occasionally, and 5 (6%) frequently. CONCLUSIONS Approximately 80% of patients with functional chest pain exhibit features of other functional disorders including IBS suggesting an overlap. This association is independent of esophageal hypersensitivity. Recognition of this overlap may facilitate better management of these patients.
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Affiliation(s)
- Ranjit S Mudipalli
- Section of Neurogastroenterology and GI Motility, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
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Remes-Troche JM, Maher J, Mudipalli R, Rao SSC. Altered esophageal sensory-motor function in patients with persistent symptoms after Nissen fundoplication. Am J Surg 2007; 193:200-5. [PMID: 17236847 DOI: 10.1016/j.amjsurg.2006.10.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2006] [Revised: 10/30/2006] [Accepted: 10/30/2006] [Indexed: 01/27/2023]
Abstract
BACKGROUND The pathophysiology of persistent gastroesophageal reflux disease (GERD) symptoms after antireflux surgery is unclear. We assessed esophageal sensorimotor function in patients with GERD before and after Nissen fundoplication (NF). METHODS Sensory and biomechanical properties were evaluated before surgery using impedance planimetry in 17 GERD patients and 16 healthy volunteers. All patients underwent standard laparoscopic NF. Eight GERD patients with persistent symptoms after surgery underwent repeat evaluations at least 12 months after surgery. RESULTS At baseline, GERD patients had lower thresholds for first perception (P < .001), discomfort (P < .001), and pain (P < .001) compared with controls. The esophagus was more reactive (P = .001) and less distensible (P = .04) in patients than controls. After NF, in patients with persistent symptoms, the sensory thresholds were unchanged (P > .05) but esophageal wall reactivity decreased (P = .001), and distensibility improved (P = .025). CONCLUSIONS NF improves esophageal biomechanical dysfunction but not the underlying hypersensitivity. Visceral hypersensitivity of the esophagus may explain persistent symptoms after NF.
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Affiliation(s)
- Jose M Remes-Troche
- Section of Neurogastroenterology, Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Dr, 4612 JCP, Iowa City, IA 52242, USA
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Ortiz Bellver V, Garrigues Gil V. [Approach to thoracic pain from the gastroenterologist's point of view]. GASTROENTEROLOGIA Y HEPATOLOGIA 2006; 29:455-62. [PMID: 17020679 DOI: 10.1157/13092565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Chest pain is common in medical consultations. One of the most frequent and serious causes is acute ischemic heart disease, which must be ruled out. The gold standard is coronary angiography. Noncardiac recurrent chest pain has a favorable prognosis. The most frequent cause is esophageal disease, with a prevalence of between 20% and 50%. The most frequent form is gastroesophageal reflux disease followed by esophageal motor disorders. Empirical treatment with high-dose proton pump inhibitors should be considered as a diagnostic-therapeutic test before performing exhaustive complementary investigations of esophageal function. Among complementary tests, manometry combined with 24-hour pH-metry has the highest diagnostic yield. Antidepressants are an acceptable therapeutic option in patients with esophageal visceral hyperalgesia.
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Affiliation(s)
- V Ortiz Bellver
- Servicio de Medicina Digestiva, Hospital Universitario La Fe, Avda. Campanar 21, 46009 Valencia, Spain
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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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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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Abstract
Various underlying mechanisms have been described in patients with non-cardiac chest pain (NCCP). By far, gastroesophageal reflux disease (GERD) is the most common cause and thus requires initial attention when patients with NCCP are managed. Esophageal dysmotility can be demonstrated in 30% of the NCCP patients, but appears to play a very limited role in symptom generation. A significant number of patients with NCCP lack any evidence of GERD and have been consistently shown to have reduced perception thresholds for pain. Peripheral and/or central sensitization have been suggested to be responsible for visceral hypersensivity in NCCP patients. Further understanding of the underlying mechanisms for pain in patients with NCCP will likely improve our current therapeutic approach.
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Affiliation(s)
- Daniel Van Handel
- The Neuro-Enteric Clinical Research Group, Department of Medicine, Section of Gastroenterology, Southern Arizona VA Health Care System and University of Arizona Health Sciences Center, Tucson, AZ 85723-0001, USA
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Abstract
Functional chest pain is a common, yet poorly understood entity. The focus of this review is to explore the evolving research and clinical approaches with a particular emphasis on the sensory or afferent neuronal dysfunction of the esophagus as a key player in the manifestation of this pain syndrome. Although once regarded as a psychologic or esophageal motility disorder, recent advances have shown that many of these patients have visceral hyperalgesia. Whether visceral hypersensitivity is a central or peripheral perturbation of the gut-brain axis remains debatable. Response to empirical therapy with high-dose proton pump inhibitors, upper endoscopy, or prolonged recording of esophageal pH may identify gastroesophageal reflux disease as a source of chest pain. Esophageal balloon distension study can serve as a useful test for identifying hypersensitivity. Newer techniques, including functional magnetic resonance imaging, magnetoencephalogram, and cortical evoked potentials, are being investigated. High doses of proton pump inhibitors and low doses of tricyclic antidepressants or trazadone remain the mainstay of therapy, although several new approaches including theophylline have been shown to be beneficial.
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Affiliation(s)
- Premjit S Chahal
- Department of Internal Medicine, University of Iowa Carver College of Medicine Iowa City, IA 52242, USA
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Abstract
Originally, sensory testing of the esophagus included the acid perfusion test and the edrophonium test, which were developed to assess patients with non-cardiac chest pain. In the last 2 decades interest in functional esophageal disorders has increased and thus further understanding of the underlying mechanisms of esophageal pain required development of new sensory testing techniques. Balloon distension using a computerized electronic device, electrical stimulation and impedance planimetry have generated important information about esophageal sensory thresholds for pain in different disease states. Intraluminal ultrasonography has been used to determine the physiologic changes of the muscle wall of the esophagus during perception of typical esophageal symptoms. Central evaluation of patients undergoing esophageal stimulation has recently been introduced to assess cerebral activation in different esophageal disorders. However, many studies using esophageal sensory testing are afflicted with significant design flaws, making interpretation of the results very difficult. This is primarily due to lack of recognition of factors that can modulate esophageal sensation.
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Affiliation(s)
- Ronnie Fass
- Neuro-Enteric Clinical Research Group, Department of Medicine, Section of Gastroenterology, Southern Arizona VA Health Care System, Tucson, Arizona 85723, USA.
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Velanovich V, Mahatme A. Effects of manometrically discovered nonspecific motility disorders of the esophagus on the outcomes of antireflux surgery. J Gastrointest Surg 2004; 8:335-41. [PMID: 15019931 DOI: 10.1016/j.gassur.2003.10.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Nonspecific motility disorders (NMDs) of the esophagus are common manometric findings in patients evaluated for gastroesophageal reflux disease (GERD). However, it is unclear how these disorders affect the outcomes of antireflux surgery. The purpose of this study was to assess symptomatic outcomes of patients with and without NMDs undergoing surgical treatment for GERD. A prospectively gathered database of all patients undergoing antireflux surgery was retrospectively reviewed for preoperative symptoms, symptom severity using the GERD-HRQL (best score 0, worst score 50), esophageal manometry measurements, presence of NMD, type of operation, any transient or permanent postoperative dysphagia, severity of postoperative dysphagia (best score 0, worst score 5), and postoperative symptom severity. A total of 239 patients were studied; 24% had a NMD identified by preoperative esophageal manometry, and 17% of this +NMD group had preoperative dysphagia or atypical chest/epigastric pain compared to 28% of those without a NMD (-NMD group) (P=NS). Preoperative symptom scores were +NMD 33 vs. -NMD 27 (P=0.01). Postoperative symptom scores were +NMD 5 vs. -NMD 3 (P=NS). There were no differences in preoperative or postoperative dysphagia scores. Transient postoperative dysphagia was 15.8% in the +NMD group vs. 16.4% in the -NMD group (P=NS). Postoperative dilation was 0% in the +NMD group vs. 2% in the -NMD group (P=NS). Manometrically discovered NMDs do not appear to affect preoperative symptoms or symptomatic outcomes of patients surgically treated for GERD. These findings my reflect the severity of GERD and may improve with antireflux surgery.
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Affiliation(s)
- Vic Velanovich
- Division of General Surgery K-8, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202-2689, USA.
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Abstract
Treatment of spastic motility disorders continues to be challenging. Therapeutic options remain limited due in part to our lack of understanding of the pathophysiology and significance of these disorders. Furthermore, most of therapeutic trials to date are hampered by the poorly designed nature of the study, including the small size of the trials and the lack of placebo arm. Most of the available information suggests that there seems to be an important dissociation between symptoms (chest pain/dysphagia) and esophageal dysmotility. Drug treatment aimed at visceral sensitivity seems more effective in relieving symptoms than spasmolytic medications. Recent trials with Botox, nitric oxide derivatives, and SSRIs offer promising results. Rigorous study design that includes large placebo-controlled trials is needed in this area.
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Affiliation(s)
- Sami R Achem
- Department of Gastroenterology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
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