5-HYDROXYTRYPTAMINE-INDUCED SYNOVIAL PLASMA EXTRAVASATION IS MEDIATEDVIA 5-HYDROXYTRYPTAMINE2A RECEPTORS ON SYMPATHETIC EFFERENT TERMINALS

5-Hydroxytryptamine (5-HT) is known to act in peripheral tissues to pr oduce pain and inflammation, yet the mechanisms underlying 5-HT-induce d inflammation have not been well studied. The present study uses a ra t knee joint model of inflammation (synovial plasma extravasation) and molecular biological techniques to determine the site of action of 5- HT and the specific 5-HT receptor subtype mediating synovial 5-HT-indu ced plasma extravasation. 5-HT (1 mu M) stimulates synovial plasma ext ravasation 7-fold above base-line revels. Surgical lumbar sympathectom y, but not C-fiber depletion by neonatal capsaicin, dramatically reduc es 5-HT-induced synovial plasma extravasation (P < .001), indicating t hat sympathetic efferents mediate this effect. Polymerase chain reacti on amplification of 5-HT receptor cDNA demonstrates that 5-HT1A, 5-HT1 B, 5-HT1D, 5-HT2A and 5-HT3, but not the 5-HT2C, receptor subtypes are present in lumbar sympathetic ganglia. With selective ligands for the se receptor subtypes, we demonstrate that 5-HT-induced synovial plasma extravasation is mediated via the 5-HT2A receptor. These findings sug gest a role for 5-HT2A antagonists in various synovial inflammatory pa in states.