title: Evidence for the participation of peripheral 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors in formalin-induced secondary mechanical allodynia and hyperalgesia.
abstract: The role of 5-HT₂A/₂B/₂C 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. Pre-treatment for five consecutive days with compound 48/80 (1, 3, 10, 10, and 10 μg/paw) prevented formalin-induced secondary allodynia and hyperalgesia. Ipsilateral, but not contralateral, peripheral pre-treatment (nmol/paw) with the 5-HT₂ receptor agonist DOI (3-30), 5-HT (10-100) or fluoxetine (0.3-3) significantly increased 0.5% formalin-induced secondary allodynia and hyperalgesia in both paws. The pronociceptive effect of DOI (10 nmol/paw), 5-HT (100 nmol/paw) and fluoxetine (1 nmol/paw) was blocked by selective 5-HT₂A (ketanserin), 5-HT₂B (RS-127445), and 5-HT₂C (RS-102221) receptor antagonists. Furthermore, ipsilateral pre-treatment (nmol/paw) with ketanserin (1, 10, and 100), RS-127445 (0.01, 0.1 and 1) or RS-102221 (1, 10 and 100) prevented while post-treatment reversed 1% formalin-induced secondary allodynia and hyperalgesia in both paws. In marked contrast, contralateral injection of the greatest tested dose of 5-HT₂A/₂B/₂C receptor antagonists did not modify long-lasting secondary allodynia and hyperalgesia. These results suggest that 5-HT released from mast cells after formalin injection sensitizes primary afferent neurons via 5-HT₂A/₂B/₂C receptors leading to the development and maintenance of secondary allodynia and hyperalgesia.
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico.
authors.forename: C
authors.initials: C
authors.lastname: Cervantes-Durán
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico.
authors.forename: J B
authors.initials: JB
authors.lastname: Pineda-Farias
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Bravo-Hernández
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico.
authors.forename: G N
authors.initials: GN
authors.lastname: Quiñonez-Bastidas
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico.
authors.forename: G C
authors.initials: GC
authors.lastname: Vidal-Cantú
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico.
authors.forename: P
authors.initials: P
authors.lastname: Barragán-Iglesias
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico. Electronic address: vgranados@prodigy.net.mx.
authors.forename: V
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D000662:Amphetamines / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D005557:Formaldehyde / Q000633:toxicity*; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D044403:Receptor, Serotonin, 5-HT2B / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D012701:Serotonin / Q000008:administration & dosage; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D000662:Amphetamines; D000700:Analgesics; D005473:Fluoxetine; D005557:Formaldehyde; D007650:Ketanserin; D011743:Pyrimidines; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D013141:Spiro Compounds; D013449:Sulfonamides; D003189:p-Methoxy-N-methylphenethylamine; C107821:8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione; C121466:2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine