ANALGESIC SYNERGISM BETWEEN AP5 (AN NMDA RECEPTOR ANTAGONIST) AND VAGINOCERVICAL STIMULATION IN THE RAT

Vaginocervical stimulation (VS) releases multiple neurotransmitters in to superfusates of the spinal cord; these car, stimulate both nocicept ive (e.g., glutamate; and glycine acting at the NMDA site), and antino ciceptive (e.g., GABA, norepinephrine, 5-HT, and glycine acting at the strychnine-sensitive receptor) systems. Although the balance between these two opposing systems can determine the nature, magnitude, and du ration of the response to VS, the characteristic prevailing response t o VS is analgesia. We hypothesized that by counteracting the nocicepti ve component of this system, the magnitude and duration of the respons e to VS would be augmented. In the present study, the NMDA receptor an tagonist AP5 [10 mu g injected intrathecally (IT)] significantly incre ased the magnitude and duration of the analgesia (measured as tail fli ck latency to radiant heat) produced by VS (200 g force). At several t ime points the analgesic effect of AP5 combined with VS was greater th an the sum of the effects of AP5 and VS separately, suggesting that th ey act synergistically. We propose that AP5 potentiates the analgesic effect of VS by two mechanisms: (a) antagonizing the putative pain-pro ducing action of glutamate and glycine acting jointly at the NMDA rece ptor, and consequently, (b) permitting the unimpeded expression of the analgesic action of inhibitory neurotransmitters released by VS (e.g. , glycine at the strychnine-sensitive receptor, and GABA). (C) 1998 El sevier Science Inc.