title: Role of peripheral and spinal 5-HT2B receptors in formalin-induced nociception.
abstract: In this study we assessed the role of local peripheral and spinal serotonin 2B (5-HT(2B)) receptors in rats submitted to the formalin test. For this, local peripheral ipsilateral, but not contralateral, administration of the highly selective 5-HT(2B) receptor antagonist 2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyridine (RS-127445, 0.01-1 nmol/paw) significantly prevented 1% formalin-induced flinching behavior. Moreover, local peripheral ipsilateral, but not contralateral, of the selective 5-HT(2) receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI, 1-10 nmol/paw) augmented 0.5% formalin-induced nociceptive behavior. The local pronociceptive effect of the 5-HT(2) receptor agonist DOI (10 nmol/paw) was significantly prevented by the local injection of RS-127445 (0.01 nmol/paw). Moreover, intrathecal injection of the selective 5-HT(2B) receptor antagonist RS-127445 (0.1-10 nmol/rat) also prevented 1% formalin-induced nociceptive behavior. In contrast, spinal injection of the 5-HT(2) receptor agonist DOI (1-10 nmol/rat) significantly increased flinching behavior induced by 0.5% formalin. The spinal pronociceptive effect of the 5-HT(2) receptor agonist DOI (10 nmol/rat) was prevented by the intrathecal injection of the 5-HT(2B) receptor antagonist RS-127445 (0.1 nmol/rat). Our results suggest that the 5-HT(2B) receptors play a pronociceptive role in peripheral as well as spinal sites in the rat formalin test. 5-HT(2B) receptors could be a target to develop analgesic drugs.
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, DF, Mexico.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cervantes-Durán
authors.forename: Guadalupe C
authors.initials: GC
authors.lastname: Vidal-Cantú
authors.forename: Paulino
authors.initials: P
authors.lastname: Barragán-Iglesias
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Pineda-Farias
authors.forename: Mariana
authors.initials: M
authors.lastname: Bravo-Hernández
authors.forename: Janet
authors.initials: J
authors.lastname: Murbartián
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D000662:Amphetamines / Q000008:administration & dosage; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D005260:Female; D007278:Injections, Spinal; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology* / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods*; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology*; D011743:Pyrimidines / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D044403:Receptor, Serotonin, 5-HT2B / Q000378:metabolism / Q000502:physiology*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000008:administration & dosage; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D000662:Amphetamines; D011743:Pyrimidines; D044403:Receptor, Serotonin, 5-HT2B; D058830:Serotonin 5-HT2 Receptor Antagonists; C121466:2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine