Peripheral 5-HT 2A receptor antagonism attenuates primary thermal hyperalgesia and secondary mechanical allodynia after thermal injury in rats

Abstract

Inflammation or injury of peripheral tissue causes release of chemical mediators, including 5-hydroxytryptamine (5-HT), which is involved in the facilitation of nociceptive transmission and the induction of hyperalgesia. The present study examined the effect of a selective 5-HT 2A receptor antagonist, sarpogrelate, on hyperalgesia and allodynia induced by thermal injury in rats. Mild thermal injury to the hindpaw produces thermal hyperalgesia in the injured area (primary thermal hyperalgesia) and mechanical allodynia in sites adjacent to the primary area (secondary mechanical allodynia). Mechanical allodynia was assessed by paw withdrawal thresholds using von Frey filaments, and thermal hyperalgesia was assessed by paw withdrawal latencies upon exposure to a radiant heat source. Intraperitoneal administration (30–100 mg/kg) or local injection (30–300 μg) of sarpogrelate 10 min prior to thermal injury attenuated secondary mechanical allodynia in a dose-dependent manner. Intraperitoneal administration (3–100 mg/kg) or local injection (30–300 μg) of sarpogrelate 10 min prior to thermal injury attenuated primary thermal hyperalgesia in a dose-dependent manner. Intraplantar injection of sarpogrelate (300 μg) to the contralateral hindpaw had no effect on primary thermal hyperalgesia or secondary mechanical allodynia in the ipsilateral paw. The tissue concentration of 5-HT was measured using microdialysis. Concentrations of 5-HT increased after thermal injury in both primary and secondary areas, and the increase was not attenuated by pretreatment with sarpogrelate (100 mg/kg, i.p.). These data suggest that 5-HT released in peripheral tissues after thermal injury sensitizes primary afferent neurons and produces mechanical allodynia and thermal hyperalgesia via peripheral 5-HT 2A receptors.