title: Serotonin induces peripheral mechanical antihyperalgesic effects in mice.
abstract: The role of serotonin (5-HT) in nociception will vary according to the subtypes of receptors activated. When administered peripherally, it induces pain in humans and in rats by activation of 5-HT1, 5-HT2 and 5-HT3 receptors. In addition, endogenous 5-HT produced in situ, is involved in the nociceptive response induced by formalin in rat's paw inflammation, possibly via 5-HT3 receptors. Moreover, it has been shown that 5-HT released in the dorsal horn of the spinal cord by stimulation of the periaqueductal gray causes activation of inhibitory interneurons, resulting in inhibition of spinal neurons. In the present study we evaluated the effect of serotonin and its receptors at peripheral antinociception. The mice paw pressure test was used in animals that had increased sensitivity by an intraplantar injection of PGE2 (2 µg). We used selective antagonists of serotonin receptors (isamoltan 5-HT1B, BRL 15572 5-HT1D, ketanserin 5-HT2A, ondansetron 5-HT3 and SB-269970 5-HT7). Administration of serotonin into the right hind paw (62.5, 125, 250 and 500 ng and 1 µg) produced a dose-dependent peripheral mechanical antihyperalgesic effect of serotonin in mice. Selective antagonists for 5-HT1B, 5-HT2A, 5-HT3 receptors at doses of 0.1, 1 and 10 µg, reversed the antihyperalgesic effect induced by 250 ng serotonin. In contrast, selective antagonists for 5-HT1D and 5-HT7 receptors were unable to reverse the antihyperalgesic effect induced by serotonin. These results demonstrated for the first time, the peripheral mechanical antihyperalgesic effect of serotonin, and participation of 5-HT1B, 5-HT2A and 5-HT3 receptors in this event.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil.
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Diniz
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil.
authors.forename: Júlia Alvarenga
authors.initials: JA
authors.lastname: Petrocchi
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil.
authors.forename: Larissa Caldeira
authors.initials: LC
authors.lastname: Navarro
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil.
authors.forename: Tâmara Cristina
authors.initials: TC
authors.lastname: Souza
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil.
authors.forename: Marina G M
authors.initials: MG
authors.lastname: Castor
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Perez
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil.
authors.forename: Igor D G
authors.initials: ID
authors.lastname: Duarte
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100 Belo Horizonte, Brazil. Electronic address: thiromero@ufmg.br.
authors.forename: Thiago R L
authors.initials: TR
authors.lastname: Romero
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051379:Mice; D017294:Ondansetron / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D001713:Biphenyl Compounds; D010636:Phenols; D010879:Piperazines; D011412:Propanolamines; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; D012701:Serotonin; D017294:Ondansetron; D007650:Ketanserin; C058392:isamoltane; D015232:Dinoprostone; C108532:BRL 15572
keywords: Peripheral antinociception; Serotonin; Serotoninergic system