Method: Reserpine (1 mg/kg) was administered subcutaneously once daily for three consecutive days to male SD rats. Muscle pressure threshold of the gastrocnemius muscle was determined using the Randall-Selitto test, and extracellular 5-HT content in the spinal cord was measured using a microdialysis system. The effect of 5-HT2C (lorcaserin, vabicaserin, and YM348), 5-HT1A (buspirone), and 5-HT2A (TCB-2) agonists on muscle pressure threshold was evaluated 5 days after the final injection of reserpine. In addition, the effect of the 5-HT2C receptor selective antagonist SB242084 was examined by injecting the agent 15 min before the administration of lorcaserin.
Result: Reserpine treatment significantly reduced extracellular content of 5-HT in the spinal cord and the muscle pressure threshold in rats. Lorcaserin (1 and 3 mg/kg, p.o.), vabicaserin (1 and 3 mg/kg, s.c.), and YM348 (0.1 and 0.3 mg/kg, p.o.) dose-dependently and significantly attenuated the reserpine-induced decrease in muscle pressure threshold, while no effect was observed with either buspirone (10 mg/kg, i.p.) or TCB-2 (2 mg/kg, i.p.). The analgesic effect of lorcaserin was significantly reversed by pretreatment with SB242084.
Conclusion: Our findings indicate that 5-HT2C receptors play a critical role in pain transmission in the reserpine-induced muscle hyperalgesia and suggest the therapeutic potential of 5-HT2C receptor agonists in treating FM.
Disclosure: S. Ogino, Astellas Pharma Inc, 3 ; M. Tsukamoto, Astellas Pharma Inc, 3 ; Y. Nagakura, Astellas Pharma Inc, 3 ; T. Watabiki, Astellas Pharma Inc, 3 ; Y. Shimizu, Astellas Pharma Inc, 3 ; H. Ito, Astellas Pharma Inc, 3 .