title: The role of transient receptor potential vanilloid 1 in mechanical and chemical visceral hyperalgesia following experimental colitis.
abstract: The transient receptor potential vanilloid 1 receptor (TRPV1) is an important nociceptor involved in neurogenic inflammation. We aimed to examine the role of TRPV1 in experimental colitis and in the development of visceral hypersensitivity to mechanical and chemical stimulation. Male Sprague-Dawley rats received a single dose of trinitrobenzenesulfonic acid (TNBS) in the distal colon. In the preemptive group, rats received the TRPV1 receptor antagonist JYL1421 (10 mumol/kg, i.v.) or vehicle 15 min prior to TNBS followed by daily doses for 7 days. In the post-inflammation group, rats received JYL1421 daily for 7 days starting on day 7 following TNBS. The visceromotor response (VMR) to colorectal distension (CRD), intraluminal capsaicin, capsaicin vehicle (pH 6.7) or acidic saline (pH 5.0) was assessed in all groups and compared with controls and naïve rats. Colon inflammation was evaluated with H&E staining and myeloperoxidase (MPO) activity. TRPV1 immunoreactivity was assessed in the thoraco-lumbar (TL) and lumbo-sacral (LS) dorsal root ganglia (DRG) neurons. In the preemptive vehicle group, TNBS resulted in a significant increase in the VMR to CRD, intraluminal capsaicin and acidic saline compared the JYL1421-treated group (P<0.05). Absence of microscopic colitis and significantly reduced MPO activity was also evident compared with vehicle-treated rats (P<0.05). TRPV1 immunoreactivity in the TL (69.1+/-4.6%) and LS (66.4+/-4.2%) DRG in vehicle-treated rats was increased following TNBS but significantly lower in the preemptive JYL1421-treated group (28.6+/-3.9 and 32.3+/-2.3 respectively, P<0.05). JYL1421 in the post-inflammation group improved microscopic colitis and significantly decreased the VMR to CRD compared with vehicle (P<0.05, >/=30 mm Hg) but had no effect on the VMR to chemical stimulation. TRPV1 immunoreactivity in the TL and LS DRG was no different from vehicle or naïve controls. These results suggest an important role for TRPV1 channel in the development of inflammation and subsequent mechanical and chemical visceral hyperalgesia.
authors: Department of Pediatrics, Division of Pediatric Gastroenterology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. amiranda@mcw.edu
authors: A
authors: A
authors: Miranda
authors: E
authors: E
authors: Nordstrom
authors: A
authors: A
authors: Mannem
authors: C
authors: C
authors: Smith
authors: B
authors: B
authors: Banerjee
authors: J N
authors: JN
authors: Sengupta
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000150:complications*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004576:Electromyography; D005727:Ganglia, Spinal / Q000166:cytology; D005769:Gastrointestinal Motility / Q000187:drug effects; D006930:Hyperalgesia / Q000145:classification / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012020:Reflex, Abdominal / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects; D017833:Visceral Afferents / Q000187:drug effects / Q000503:physiopathology
chemical_list: C466314:JYL 1421; D013449:Sulfonamides; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014302:Trinitrobenzenesulfonic Acid; D013890:Thiourea; D002211:Capsaicin
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