The role of transient receptor potential vanilloid 1 in mechanical and chemical visceral hyperalgesia following experimental colitis

Miranda, Adrian; Nordstrom, Eric; Mannem, Arun; Smith, Cass R.; Banerjee, Banani; Sengupta, Jyoti N.

doi:10.1016/j.neuroscience.2007.05.034

Cited by 141 publications

(119 citation statements)

References 60 publications

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“…Animal experiments have demonstrated an important role for TRPV1 both in gastro-esophageal (Bielefeldt and Davis, 2008), small intestinal (Rong et al, 2004) and colonic visceral mechanosensitivity as well as in hypersensitivity induced by intracolonic administration of zymosan or neonatal irritation of the colon (Winston et al, 2007). In addition, TRPV1 was shown to be up-regulated in nociceptive visceral afferents of rodents with experimental trinitrobenzene sulfonic acid (TNBS)-induced colitis (Miranda et al, 2007;De Schepper et al, 2008a). De Schepper et al showed that acute TNBS-induced colitis increased the response to colorectal distention in rat pelvic afferent C fibres but not in Ad fibres.…”

Section: Trpv Channelsmentioning

confidence: 99%

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: 99%

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

Boesmans

Owsianik

Tack

et al. 2010

British J Pharmacology

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“…TRPV1 knockout (KO) mice exhibit reduced responses of stretch-sensitive afferents (20) and decreased behavioral responses to colorectal distension (CRD) (19) in both naive and hypersensitive states. TRPV1 antagonists similarly decrease afferent and behavioral responses to CRD (9,29,31,52).…”

mentioning

confidence: 93%

Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

Kiyatkin

Feng

Schwartz

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Kiyatkin ME, Feng B, Schwartz ES, Gebhart GF. Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization. Am J Physiol Gastrointest Liver Physiol 305: G638 -G648, 2013. First published August 29, 2013; doi:10.1152/ajpgi.00180.2013.-The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined channel contributions to behavioral responses to colorectal distension (CRD) and afferent fiber responses to colorectal stretch. Baseline responses to CRD were unexpectedly greater in TPDKO compared with control mice, but zymosan-produced CRD hypersensitivity was absent in TPDKO mice. Relative to control mice, proportions of mechanosensitive and -insensitive pelvic nerve afferent classes were not different in TPDKO mice. Responses of mucosal and serosal class afferents to mechanical probing were unaffected, whereas responses of muscular (but not muscular/mucosal) afferents to stretch were significantly attenuated in TPDKO mice; sensitization of both muscular and muscular/mucosal afferents by inflammatory soup was also significantly attenuated. In pharmacological studies, the TRPV1 antagonist A889425 and P2X3 antagonist TNP-ATP, alone and in combination, applied onto stretch-sensitive afferent endings attenuated responses to stretch; combined antagonism produced greater attenuation. In the aggregate, these observations suggest that 1) genetic manipulation of TRPV1 and P2X3 leads to reduction in colorectal mechanosensation peripherally and compensatory changes and/or disinhibition of other channels centrally, 2) combined pharmacological antagonism produces more robust attenuation of mechanosensation peripherally than does antagonism of either channel alone, and 3) the relative importance of these channels appears to be enhanced in colorectal hypersensitivity. pelvic nerve; purinergic receptor; single fiber; transient receptor potential; visceral pain CHRONIC ABDOMINAL PAIN is a key feature of irritable bowel syndrome (IBS), which is prevalent, costly, and difficult to manage. An important contributor to pain in IBS is heightened perception of mechanical events in the bowel (i.e., hypersensitivity). Indeed, patients with IBS typically report greater pain and/or reduced response thresholds to rectal balloon distension than control subjects (3,24,28,34,46). Although central processes contribute to colorectal hypersensitivity, the driving force is increased afferent mechanosensitivity (i.e., sensitization). For example, intrarectal lidocaine reduces pain evoked by rectal distension in healthy subjects as well as ongoing pain and both vi...

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“…In a model of colonic hypersensitivity induced by neonatal colonic irritation in rats [81], TRPV1 inhibitors were effective in reducing pain responses to colorectal distension. Increased expression of TRPV1 in DRG is evident in this model, as well as in a TNBS colitis model [82], suggesting that TRPV1 up-regulation may be a mechanism by which the effect of a TRPV1 antagonist becomes manifest. This mechanism was also evident In a model of pancreatic inflammation [83].…”

Section: Changes In Sensory Signalling In Diseasementioning

confidence: 69%

“…This mechanism was also evident In a model of pancreatic inflammation [83]. The up-regulation of function via TRPV1 can be long-term, and may lead to cascades of events resulting in hypersensitivity [81,82]. Alternatively, the translocation of TRPV1 to the cell membrane may have an important influence on its function without changes in mRNA expression [84].…”

Section: Changes In Sensory Signalling In Diseasementioning

confidence: 90%

TRP Channels in Visceral Pain

Blackshaw¹,

Brierley²,

Harrington³

et al. 2013

TOPAINJ

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Visceral pain is both different and similar to somatic pain - different in being poorly localized and usually referred elsewhere to the body wall, but similar in many of the molecular mechanisms it employs (like TRP channels) and the specialization of afferent endings to detect painful stimuli. TRPV1 is sensitive to low pH. pH is lowest in gastric juice, which may cause severe pain when exposed to the oesophageal mucosa, and probably works via TRPV1. TRPV1 is found in afferent fibres throughout the viscera, and the TRPV1 agonist capsaicin can recapitulate symptoms experienced in disease. TRPV1 is also involved in normal mechanosensory function in the gut. Roles for TRPV4 and TRPA1 have also been described in visceral afferents, and TRPV4 is highly enriched in them, where it plays a major role in both mechanonociception and chemonociception. It may provide a visceral-specific nociceptor target for drug development. TRPA1 is also involved in mechano-and chemosensory function, but not as selectively as TRPV4. TRPA1 is colocalized with TRPV1 in visceral afferents, where they influence each other's function. Another modulator of TRPV1 is the cool/mint receptor TRPM8, which, when activated can abrogate responses mediated via TRPV1, suggesting that TRPM8 agonists may provide analgesia via this pathway. In all, the viscera are rich in TRP channel targets on nociceptive neurones which we hope will provide opportunities for therapeutic analgesia.

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The role of transient receptor potential vanilloid 1 in mechanical and chemical visceral hyperalgesia following experimental colitis

Cited by 141 publications

References 60 publications

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

TRP Channels in Visceral Pain

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