title: Mechanisms involved in abdominal nociception induced by either TRPV1 or TRPA1 stimulation of rat peritoneum.
abstract: Abdominal pain is a frequent symptom of peritoneal cavity irritation, but little is known about the role of the receptors for irritant substances, transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1), in this painful condition. Thus, we investigated the abdominal nociception caused by peritoneal stimulation with TRPV1 (capsaicin) and TRPA1 (allyl isothiocyanate, AITC) agonists and their mechanisms in rats. The intraperitoneal (i.p.) injection of either capsaicin or AITC (0.03-10 mg/kg) induced short-term (up to 20 min) and dose-dependent abdominal nociception, and also produced c-fos expression in spinal afferents of the dorsal horn. TRPV1 antagonism prevented (94 ± 4% inhibition) nociception induced by capsaicin but not by AITC. In contrast, the TRPA1 antagonism almost abolished AITC-induced nociception (95 ± 2% inhibition) without altering the capsaicin response. Moreover, nociception induced by either capsaicin or AITC was reduced by the desensitisation of TRPV1-positive sensory fibres with resiniferatoxin (73 ± 18 and 76 ± 15% inhibitions, respectively) and by the NK1 receptor antagonist aprepitant (56 ± 5 and 53 ± 8% inhibitions, respectively). Likewise, the i.p. injections of capsaicin or AITC increased the content of substance P in the peritoneal fluid. Nevertheless, neither the mast cell membrane stabiliser cromoglycate, nor the H1 antagonist promethazine, nor depletion of peritoneal macrophages affected abdominal nociception induced either by capsaicin or AITC. Accordingly, neither capsaicin nor AITC increased the histamine content in the peritoneal fluid or provoked peritoneal mast cell degranulation in vitro. Collectively, our findings suggest that TRPV1 and TRPA1 stimulation in the peritoneum produces abdominal nociception that is mediated by sensory fibres activation.
authors.affiliation: Graduate Program in Biological Sciences, Toxicological Biochemistry, Department of Chemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS 97105-900, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Trevisan
authors.forename: Mateus F
authors.initials: MF
authors.lastname: Rossato
authors.forename: Carin
authors.initials: C
authors.lastname: Hoffmeister
authors.forename: Sara M
authors.initials: SM
authors.lastname: Oliveira
authors.forename: Cássia R
authors.initials: CR
authors.lastname: Silva
authors.forename: Filipe C
authors.initials: FC
authors.lastname: Matheus
authors.forename: Gláucia C
authors.initials: GC
authors.lastname: Mello
authors.forename: Edson
authors.initials: E
authors.lastname: Antunes
authors.forename: Rui D S
authors.initials: RD
authors.lastname: Prediger
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D005772:Gastrointestinal Transit / Q000187:drug effects; D007422:Intestines / Q000187:drug effects / Q000502:physiology; D017879:Isothiocyanates / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects; D059225:Nociception / Q000187:drug effects; D010537:Peritoneum / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000819:agonists / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000819:agonists / Q000378:metabolism*
chemical_list: D017879:Isothiocyanates; D018040:Receptors, Neurokinin-1; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels; C480976:Trpa1 protein, rat; C493922:Trpv1 protein, rat; D013373:Substance P; C004471:allyl isothiocyanate; D002211:Capsaicin
keywords: Allyl isothiocyanate; Capsaicin; Mast cells; Pain; Resiniferatoxin; Substance p