title: Role of TRPV1 in high-threshold rat colonic splanchnic afferents is revealed by inflammation.
abstract: The vanilloid-1 receptor TRPV1 is known to play a role in extrinsic gastrointestinal afferent function. We investigated the role of TRPV1 in mechanosensitivity in afferents from normal and inflamed tissue. Colonic mechanosensitivity was determined in an in vitro rat colon preparation by recording from attached splanchnic nerves. Recordings were made from serosal/mesenteric afferents responding only at high thresholds to graded mechanical stimulation with von Frey probes. Colonic inflammation was induced by adding 5% dextran sulphate sodium (DSS) to the drinking water for 5 days, and was confirmed by histopathology. The selective TRPV1 antagonist, SB-750364 (10(-8) to 10(-6)M), was tested on mechanosensory stimulus response functions of afferents from normal and inflamed preparations (N=7 each). Mechanosensory responses had thresholds of 1-2g, and maximal responses were observed at 12 g. The stimulus response function was not affected by DSS-induced colitis. SB-750364 had no effect on stimulus response functions in normal preparations, but reduced (up to 60%) in a concentration-dependent manner those in inflammation (2-way ANOVA, p<0.05). Moreover, in inflamed tissue, spontaneous afferent activity showed a dose-dependent trend toward reduction with SB-750364. We conclude that mechanosensitivity of high-threshold serosal colonic splanchnic afferents to graded stimuli is unaffected during DSS colitis. However, there is a positive influence of TRPV1 in mechanosensitivity in inflammation, suggesting up-regulation of excitatory TRPV1-mediated mechanisms.
authors.affiliation: Nerve-Gut Research Laboratory, Hanson Institute, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Phillis
authors.forename: Chris M
authors.initials: CM
authors.lastname: Martin
authors.forename: Daiwu
authors.initials: D
authors.lastname: Kang
authors.forename: Håkan
authors.initials: H
authors.lastname: Larsson
authors.forename: Erik A
authors.initials: EA
authors.lastname: Lindström
authors.forename: Vicente
authors.initials: V
authors.lastname: Martinez
authors.forename: L Ashley
authors.initials: LA
authors.lastname: Blackshaw
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D003106:Colon / Q000276:immunology* / Q000294:innervation / Q000502:physiology; D016264:Dextran Sulfate / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D008839:Microelectrodes; D009475:Neurons, Afferent / Q000276:immunology* / Q000502:physiology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000008:administration & dosage; D013153:Splanchnic Nerves / Q000276:immunology* / Q000502:physiology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018689:Sensory System Agents; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D016264:Dextran Sulfate