Patterns of serotonin- and 2-methylserotonin-induced pain may reflect 5-HT3 receptor sensitization

Intraperitoneal injection of serotonin (5-HT; 0.5-4.0 mg/kg) produced dose-dependent nociceptive writhing responses, attenuated at all doses by pre-administration of tropisetron (1.0 mg/kg, i.p.). Administration of 2-methylserotonin (2-methyl-5-HT) alone was ineffective in inducing writhing. The effects of 5-HT (0.5 mg/kg, i.p.) were increased by subsequent injection of 2-methyl-5-HT (0.5-4.0 mg/kg, i.p.). The enhanced nociceptive responses produced by low dose of 5-HT and subsequently administered 2-methyl-5-HT were attenuated by pretreatment with tropisetron. These results suggest that the inflammatory cascade produced by peripheral administration of 5-HT evokes nociception by stimulating visceral 5-HT3 receptors and that 5-HT-induced mechanisms appear to sensitize the 5-HT3 receptor to subsequent pharmacologic activation. (C) 2003 Published by Elsevier B.V.