5-HT1A RECEPTORS MEDIATE THE EFFECT OF THE BULBOSPINAL SEROTONIN SYSTEM ON SPINAL DORSAL HORN NOCICEPTIVE NEURONS

The present study examined whether the effect of stimulation of the nucleus raphe magnus (NRM) is mediated by spinal cord dorsal horn serotonin(1A) (5-HT1A) receptors in the rat. This hypothesis predicts that nociceptive dorsal horn units inhibited by NRM stimulation or iontophoretic 5-HT application would also be inhibited by iontophoresis of the selective 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and buspirone. A total of 78 dorsal horn wide-dynamic-range neurons were recorded. Overall, 62% of the cells tested (48/78) were responsive to electrical stimulation of the NRM with the predominant response being inhibitory (38/48; 79%). Fifty-eight cells were tested for their response to both NRM stimulation and 8-OH-DPAT iontophoresis: 20/58 cells were inhibited by NRM stimulation and 50% of the cells inhibited by NRM stimulation were also inhibited by 8-OH-DPAT. Fifty-two cells were tested for their response to both NRM stimulation and buspirone iontophoresis: 14/52 cells were inhibited by NRM stimulation with 9/14 similarly inhibited by buspirone. To examine whether exogenously applied serotonin produced an effect through 5-HT1A receptors, the effect of both 5-HT and 8-OH-DPAT iontophoresis was tested on 57 dorsal horn neurons. The majority of cells (25/57) were inhibited by 5-HT application; 15/25 were similarly inhibited by 8-OH-DPAT. The response of 48 dorsal horn cells to 5-HT and buspirone iontophoresis was compared. Forty-four percent (21/48) of the cells were inhibited by 5-HT; 16/21 were also inhibited by buspirone. The present data support the hypothesis that 5-HT1A receptors mediate the inhibitory effect of the NRM descending 5-HT pathway on spinal pain transmission. These results are surprising in that 5-HT1A receptors represent approximately 25-35% of dorsal horn 5-HT receptors and that the 5-HT system is only one of several descending bulbospinal pathways arising from the NRM.