Receptor Mediation of 5-HT-induced Inflammation and Nociception in Rats

In light of evidence suggesting the proinflammatory and nociceptive action of peripheral serotonin (5-HT), the present study examined dose-dependent parameters of edema and algesia produced by intraplantar injections of 5-HT and the role of heterogeneous 5-HT receptors in these 5-HT-induced responses. Intraplantar 5-HT (0.05, 0.25, 0.5, or 1.0 mumols) produced paw edema at each 5-HT concentration and produced concentration-dependent increases in the nociceptive response as indexed by lifts of, and licks to the affected paw. Intraplantar pretreatment with the 5-HT1 receptor antagonist methysergide at concentrations greater than or equal to 3 nmol attenuated the 5-HT-induced (25 mumols) inflammatory and nociceptive responses. At concentrations greater than or equal to 300 nmol, both 5-HT2 receptor antagonist ketanserin and 5-HT3 receptor antagonist odansetron pretreatment blocked 5-HT-induced inflammatory and nociceptive responses. These results more completely define peripheral 5-HT-receptor-dependent systems of 5-HT-induced inflammation and nociception in rats.