title: A novel mechanism involved in 5-hydroxytryptamine-induced nociception: the indirect activation of primary afferents.
abstract: The aim of this study was to test the hypothesis that 5-hydroxytryptamine induces nociception by an indirect action on the primary afferent nociceptor in addition to its previously described direct action. Injection of 5-hydroxytryptamine into the s.c. tissue of the hind paw of rats produced nociceptive flinch behavior and inflammatory cell migration, that were significantly reduced by the nonspecific selectin inhibitor fucoidan. 5-Hydroxytryptamine-induced nociception was also significantly reduced by local blockade of the 5-HT3 receptor by tropisetron, by the cyclooxygenase inhibitor indomethacin and by local blockade of the beta1-adrenergic receptor or of the D1 receptor by atenolol or SCH 23390, respectively. Neither guanethidine depletion of norepinephrine in the sympathetic terminals nor local blockade of the beta2-adrenergic receptor by ICI-118,551 significantly reduced 5-hydroxytryptamine-induced nociception. Taken together, these findings indicate that 5-hydroxytryptamine induces nociception by a novel, indirect and norepinephrine-independent mechanism mediated by neutrophil migration and local release of prostaglandin and dopamine. Furthermore, to test whether dopamine acts on beta1-adrenergic and/or D1 receptor to contribute to 5-hydroxytryptamine-induced nociception, dopamine was s.c. injected either alone or combined with atenolol or with SCH 23390. S.c.-injected dopamine also produced a dose-dependent nociceptive behavior that was significantly reduced by both SCH 23390 and atenolol. Based on that it is proposed that dopamine, once released, activates D1 and beta1-adrenergic receptors to contribute to 5-hydroxytryptamine-induced nociception.
authors.affiliation: Department of Physiology, Laboratory of Orofacial Pain, Faculty of Dentistry of Piracicaba, University of Campinas, UNICAMP, 901 Limeira Avenue, Piracicaba, São Paulo 13414-900, Brazil. tambeli@fop.unicamp.br
authors.forename: C H
authors.initials: CH
authors.lastname: Tambeli
authors.forename: M C G
authors.initials: MC
authors.lastname: Oliveira
authors.forename: J T
authors.initials: JT
authors.lastname: Clemente
authors.forename: A
authors.initials: A
authors.lastname: Pelegrini-da-Silva
authors.forename: C A
authors.initials: CA
authors.lastname: Parada
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D001522:Behavior, Animal; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000139:chemically induced* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D011134:Polysaccharides / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000633:toxicity*; D018490:Serotonin Agents / Q000633:toxicity*; D013997:Time Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D001552:Benzazepines; D018492:Dopamine Antagonists; D011134:Polysaccharides; D011412:Propanolamines; D018490:Serotonin Agents; D012701:Serotonin; C026777:ICI 118551; D001262:Atenolol; C007789:fucoidan; D007213:Indomethacin