Mechanisms involved in abdominal nociception induced by either TRPV1 or TRPA1 stimulation of rat peritoneum

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• 作者：Gabriela Trevisan ; Mateus F. Rossato ; Carin Hoffmeister ; Sara M. Oliveira ; C¨¢ssia R. Silva ; Filipe C. Matheus ; Gl¨¢ucia C. Mello ; Edson Antunes ; Rui D.S. Prediger ; Juliano Ferreira
• 关键词：Capsaicin ; Allyl isothiocyanate ; Substance p ; Mast cells ; Resiniferatoxin ; Pain
• 刊名：European Journal of Pharmacology
• 出版年：2013
• 出版时间：15 August, 2013
• 年：2013
• 卷：714
• 期：1-3
• 页码：332-344
• 全文大小：2004 K

文摘

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¡À4 % inhibition) nociception induced by capsaicin but not by AITC. In contrast, the TRPA1 antagonism almost abolished AITC-induced nociception (95¡À2 % 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¡À18 and 76¡À15 % inhibitions, respectively) and by the NK1 receptor antagonist aprepitant (56¡À5 and 53¡À8 % 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.