Received for publication November 13, 2006.
Revised January 25, 2007.
Accepted for publication February 27, 2007.

Roles of 5-HT receptor subtypes in the inhibitory effects of 5-HT on C-fiber responses of spinal wide dynamic range neurons in rats

Abstract

5-Hydroxytryptamine (5-HT, or serotonin) plays an important role in the descending control of nociception. 5-HT and its receptors have been extensively studied in the modulation of nociceptive transmission at the spinal level using behavioral tests that may be affected by the effects of 5-HT on motor performance and skin temperature. Using electrophysiological methods, the present study aimed to systematically investigate the roles of 5-HT receptor subtypes on the inhibitory effects of 5-HT on responses of the spinal wide dynamic range (WDR) neurons to C-fiber inputs in rats. Under basal conditions, topical application of 5-HT to the spinal cord inhibited the C-fiber responses of WDR neurons dose-dependently, whereas antagonists of 5-HT_1A (WAY 100635), 5-HT_1B (GR 55562), 5-HT_2A (ketanserin), 5-HT_2C (RS 102221), 5-HT₃ (MDL 72222) and 5-HT₄ (GR 113808) had no effect on their own. The inhibitory effects of 5-HT were reversed by antagonists of 5-HT_1B (GR 55562), 5-HT_2A (ketanserin), 5-HT_2C (RS 102221), 5-HT₃ (MDL 72222) and 5-HT₄ (GR 113808), but not by 5-HT_1A (WAY 100635), receptor antagonists. Topical administration of agonists of 5-HT_1A (8-OH-DPAT), 5-HT_1B (CGS 12066), 5-HT_2A (-m-5-HT), 5-HT_2C (MK 212), 5-HT₃ (mCPBG) and 5-HT₄ (BZTZ) also inhibited the C-responses. These results suggest that under basal conditions there is no tonic serotonergic inhibition on the C-responses of dorsal horn neurons and multiple 5-HT receptor subtypes including 1B, 2A, 2C, 3 and 4 may be involved in mediating the inhibitory effects of 5-HT.

Key words: 5-Hydroxytryptamine, 5-Hydroxytryptamine receptors, Electrophysiology, Rat, Spinal cord, Wide dynamic range neurons