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 nu cleus raphe magnus (NRM) is mediated by spinal cord dorsal horn seroto nin(1A) (5-HT1A) receptors in the rat. This hypothesis predicts that n ociceptive dorsal horn units inhibited by NRM stimulation or iontophor etic 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 neu rons were recorded. Overall, 62% of the cells tested (48/78) were resp onsive to electrical stimulation of the NRM with the predominant respo nse being inhibitory (38/48; 79%). Fifty-eight cells were tested for t heir response to both NRM stimulation and 8-OH-DPAT iontophoresis: 20/ 58 cells were inhibited by NRM stimulation and 50% of the cells inhibi ted by NRM stimulation were also inhibited by 8-OH-DPAT. Fifty-two cel ls were tested for their response to both NRM stimulation and buspiron e iontophoresis: 14/52 cells were inhibited by NRM stimulation with 9/ 14 similarly inhibited by buspirone. To examine whether exogenously ap plied serotonin produced an effect through 5-HT1A receptors, the effec t of both 5-HT and 8-OH-DPAT iontophoresis was tested on 57 dorsal hor n neurons. The majority of cells (25/57) were inhibited by 5-HT applic ation; 15/25 were similarly inhibited by 8-OH-DPAT. The response of 48 dorsal horn cells to 5-HT and buspirone iontophoresis was compared. F orty-four percent (21/48) of the cells were inhibited by 5-HT; 16/21 w ere also inhibited by buspirone. The present data support the hypothes is that 5-HT1A receptors mediate the inhibitory effect of the NRM desc ending 5-HT pathway on spinal pain transmission. These results are sur prising in that 5-HT1A receptors represent approximately 25-35% of dor sal horn 5-HT receptors and that the 5-HT system is only one of severa l descending bulbospinal pathways arising from the NRM.