Role of peripheral and spinal 5-HT2B receptors in formalin-induced nociception

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2012-07, Vol.102 (1), p.30-35
• Main Authors: Cervantes-Durán, Claudia, Vidal-Cantú, Guadalupe C., Barragán-Iglesias, Paulino, Pineda-Farias, Jorge B., Bravo-Hernández, Mariana, Murbartián, Janet, Granados-Soto, Vinicio
• Format: Article
• Language: English
• Subjects: 5-HT2B receptors; Amphetamines - administration & dosage; Analgesics; Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; DOI; Drugs; Female; Formaldehyde; Injections, Spinal; Pain - metabolism; Pain - physiopathology; Pain - prevention & control; Pain Measurement - drug effects; Pain Measurement - methods; Pain perception; Peripheral Nerves - drug effects; Peripheral Nerves - physiology; Pyrimidines - administration & dosage; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2B - metabolism; Receptor, Serotonin, 5-HT2B - physiology; RS-127445; Serotonin 5-HT2 Receptor Antagonists - administration & dosage; Serotonin S2 receptors; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord - physiopathology; Spinal processing
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2012.03.015

In this study we assessed the role of local peripheral and spinal serotonin 2B (5-HT2B) receptors in rats submitted to the formalin test. For this, local peripheral ipsilateral, but not contralateral, administration of the highly selective 5-HT2B receptor antagonist 2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyridine (RS-127445, 0.01–1nmol/paw) significantly prevented 1% formalin-induced flinching behavior. Moreover, local peripheral ipsilateral, but not contralateral, of the selective 5-HT2 receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI, 1–10nmol/paw) augmented 0.5% formalin-induced nociceptive behavior. The local pronociceptive effect of the 5-HT2 receptor agonist DOI (10nmol/paw) was significantly prevented by the local injection of RS-127445 (0.01nmol/paw). Moreover, intrathecal injection of the selective 5-HT2B receptor antagonist RS-127445 (0.1–10nmol/rat) also prevented 1% formalin-induced nociceptive behavior. In contrast, spinal injection of the 5-HT2 receptor agonist DOI (1–10nmol/rat) significantly increased flinching behavior induced by 0.5% formalin. The spinal pronociceptive effect of the 5-HT2 receptor agonist DOI (10nmol/rat) was prevented by the intrathecal injection of the 5-HT2B receptor antagonist RS-127445 (0.1nmol/rat). Our results suggest that the 5-HT2B receptors play a pronociceptive role in peripheral as well as spinal sites in the rat formalin test. 5-HT2B receptors could be a target to develop analgesic drugs. ► Peripheral and spinal RS-127445 prevented formalin-induced flinching behavior. ► Peripheral and spinal DOI increased formalin-induced nociceptive behavior. ► The pronociceptive effect of DOI was significantly prevented by RS-127445. ► Data suggest that peripheral/spinal 5-HT2B receptors play a pronociceptive role.