Increased capsaicin receptor TRPV1 nerve fibres in the inflamed human oesophagus

Matthews, Philip J; Aziz, Qasim; Facer, P.; Davis, John B.; Thompson, David G.; Anand, Praveen

doi:10.1097/00042737-200409000-00014

Cited by 252 publications

(174 citation statements)

References 25 publications

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“…Here, TRPV1 immunoreactivity is increased in mucosal biopsies from patients with erosive (Matthews et al, 2004) and non-erosive esophagitis (Bhat and Bielefeldt, 2006) and it is expected that TRPV1 also plays a key role in the pathogenesis of symptoms associated with reflux (Ang et al, 2008). In keeping with this hypothesis, intra-esophageal capsaicin installation was found to induce symptoms of heartburn and chest pain in healthy volunteers (Kindt et al, 2009).…”

Section: Trpv Channelsmentioning

confidence: 85%

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

Boesmans

Owsianik

Tack

et al. 2010

British J Pharmacology

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The members of the superfamily of transient receptor potential (TRP) cation channels are involved in a plethora of cellular functions. During the last decade, a vast amount of evidence is accumulating that attributes an important role to these cation channels in different regulatory aspects of the alimentary tract. In this review we discuss the expression patterns and roles of TRP channels in the regulation of gastrointestinal motility, enteric nervous system signalling and visceral sensation, and provide our perspectives on pharmacological targeting of TRPs as a strategy to treat various gastrointestinal disorders. We found that the current knowledge about the role of some members of the TRP superfamily in neurogastroenterology is rather limited, whereas the function of other TRP channels, especially of those implicated in smooth muscle cell contractility (TRPC4, TRPC6), visceral sensitivity and hypersensitivity (TRPV1, TRPV4, TRPA1), tends to be well established. Compared with expression data, mechanistic information about TRP channels in intestinal pacemaking (TRPC4, TRPC6, TRPM7), enteric nervous system signalling (TRPCs) and enteroendocrine cells (TRPM5) is lacking. It is clear that several different TRP channels play important roles in the cellular apparatus that controls gastrointestinal function. They are involved in the regulation of gastrointestinal motility and absorption, visceral sensation and visceral hypersensitivity. TRP channels can be considered as interesting targets to tackle digestive diseases, motility disorders and visceral pain. At present, TRPV1 antagonists are under development for the treatment of heartburn and visceral hypersensitivity, but interference with other TRP channels is also tempting. However, their role in gastrointestinal pathophysiology first needs to be further elucidated.

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Section: Trpv Channelsmentioning

confidence: 85%

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

Boesmans

Owsianik

Tack

et al. 2010

British J Pharmacology

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“…To the best of our knowledge, only 2 other studies have looked for the presence of TRPV1 in the human esophagus. Matthews et al 17 found that patients with erosive esophagitis had an increased number of TRPV1 positive papillae as compared to normal controls (30% versus 11.8% of total papillae). Bhat and Bielefeldt 16 noticed TRPV1 positivity in 23% of the papillae.…”

Section: Discussionmentioning

confidence: 99%

“…We also observed TRPV1 immunostaining pattern in the esophageal mucosa that is consistent with the findings of others. 16,17 Ours is the first study of injection of acid and capsaicin into the mucosa/submucosa of the human esophagus, and raises questions regarding the prevailing hypothesis of how acid reflux causes esophageal pain and heartburn.…”

Section: Discussionmentioning

confidence: 99%

Esophageal Submucosal Injection of Capsaicin but Not Acid Induces Symptoms in Normal Subjects

Lee

Korsapati

Bhalla

et al. 2016

J Neurogastroenterol Motil

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Background/AimsTransient receptor potential vanilloid-1 (TRPV1) is a candidate for mediating acid-induced symptoms in the esophagus. We conducted studies to determine if the presence of acid in the mucosa/submucosa and direct activation of TRPV1 by capsaicin elicited symptoms in normal healthy subjects. We also studied the presence of TRPV1 receptors in the esophagus. MethodsUnsedated endoscopy was performed on healthy subjects with no symptoms. Using a sclerotherapy needle, normal saline (pH 2.0-7.5) was injected into the mucosa/submucosa, 5 cm above the Z line. In a separate group of healthy subjects, injection of capsaicin and vehicle was also studied. Quality of symptoms was reported using the McGill Pain Questionnaire, and symptom intensity using the visual analogue scale (VAS). Immunohistochemistry was performed on 8 surgical esophagus specimens using TRPV1 antibody. ResultsAcid injection either did not elicit or elicited mild symptoms in subjects at all pH solutions. Capsaicin but not the vehicle elicited severe heartburn/chest pain in all subjects. Mean VAS for capsaicin was 91 ± 3 and symptoms lasted for 25 ± 1 minutes. Immunohistochemistry revealed a linear TRPV1 staining pattern between the epithelial layer and the submucosa that extended into the papillae. Eighty-five percent of papillae stained positive for TRPV1 with a mean 1.1 positive papillae per high-powered field. ConclusionsThe mechanism of acid-induced heartburn and chest pain is not the simple interaction of hydrogen ions with afferents located in the esophageal mucosa and submucosa. TRPV1 receptors are present in the lamina propria and their activation induces heartburn and chest pain.

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“…An increased expression of TRPV1 is found in several conditions characterized by general hypersensitivity, such as thermal hyperagesia, vulvodynia, rectal hypersensitivity, esophagitis, and chronic cough [13][14][15][16][17][18]. Recently, it has been found that ethanol potentiates the response of TRPV1 to capsaicin in different organs in rats and guinea pigs [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Inhaled ethanol potentiates the cough response to capsaicin in patients with airway sensory hyperreactivity

Millqvist

Ternesten-Hasséus

Bende

2008

Pulmonary Pharmacology & Therapeutics

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To cite this version:Eva Millqvist, Ewa Ternesten-Hasséus, Mats Bende. Inhaled ethanol potentiates the cough response to capsaicin in patients with airway sensory hyperreactivity. Pulmonary Pharmacology & Therapeutics, 2008, 21 (5) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d m a n u s c r i p t 4

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Increased capsaicin receptor TRPV1 nerve fibres in the inflamed human oesophagus

Abstract: TRPV1-immunoreactive sensory nerve fibres are expressed in human oesophageal mucosa both in health and in disease. Increased TRPV1 expression in the inflamed oesophagus may mediate the heartburn in oesophagitis, and TRPV1 blockers may provide novel treatment.

Cited by 252 publications

References 25 publications

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

Esophageal Submucosal Injection of Capsaicin but Not Acid Induces Symptoms in Normal Subjects

Inhaled ethanol potentiates the cough response to capsaicin in patients with airway sensory hyperreactivity

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