title: Role of peripheral and spinal 5-HT(3) receptors in development and maintenance of formalin-induced long-term secondary allodynia and hyperalgesia.
abstract: The role of peripheral and spinal 5-HT(3) receptors in formalin-induced secondary allodynia and hyperalgesia in rats was assessed. Formalin produced acute nociceptive behaviors (flinching and licking/lifting) followed by long-term secondary mechanical allodynia and hyperalgesia in both paws. In experiments where the test drug was anticipated to augment or antagonize the response, 0.5 or 1% formalin, respectively, was used for injection. Peripheral ipsilateral, but not contralateral, pre-treatment (-10 min) with serotonin (5-HT, 10-100 nmol/paw) and the selective 5-HT(3) receptor agonist 1-(m-chlorophenyl)-biguanide (m-CPBG, 10-300 nmol/paw) increased 0.5% formalin-induced secondary allodynia and hyperalgesia in both paws. Moreover, spinal pre-treatment with m-CPBG (10-300 nmol/rat) increased 0.5% formalin-induced secondary hyperalgesia but not allodynia in both paws. Accordingly, peripheral ipsilateral (30-300 nmol/paw), but not contralateral (300 nmol/paw), and spinal (10-100 nmol) pre-treatment with the selective 5-HT(3) receptor antagonist ondansetron prevented 1% formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. The peripheral pronociceptive effects of 5-HT (100 nmol/paw) and m-CPBG (300 nmol/paw) as well as the spinal effect of m-CPBG (300 nmol/rat) were completely prevented by the peripheral (10 nmol/paw) and spinal (1 nmol/rat) injection, respectively, of ondansetron. At these doses, ondansetron did not modify per se formalin-induced nociceptive behaviors. Spinal (30-300 nmol/rat), but not peripheral (300 nmol/paw), post-treatment (on day 6) with ondansetron reversed established formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. Results suggest that a barrage of afferent input induced by 5-HT at peripheral 5-HT(3) receptors participates in the development of formalin-induced long-term secondary allodynia and hyperalgesia in the rat. In addition, our data suggest that spinal 5-HT(3) receptors play an important role during development and maintenance of these evoked long-term behaviors.
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico.
authors.forename: Mariana
authors.initials: M
authors.lastname: Bravo-Hernández
authors.forename: Claudia
authors.initials: C
authors.lastname: Cervantes-Durán
authors.forename: Jorge Baruch
authors.initials: JB
authors.lastname: Pineda-Farias
authors.forename: Paulino
authors.initials: P
authors.lastname: Barragán-Iglesias
authors.forename: Pedro
authors.initials: P
authors.lastname: López-Sánchez
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D044406:Receptors, Serotonin, 5-HT3