Analgesic Synergism Between AP5 (an NMDA Receptor Antagonist) and Vaginocervical Stimulation in the Rat

Abstract

Vaginocervical stimulation (VS) releases multiple neurotransmitters into superfusates of the spinal cord; these can stimulate both nociceptive (e.g., glutamate, and glycine acting at the NMDA site), and antinociceptive (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 duration of the response to VS, the characteristic prevailing response to VS is analgesia. We hypothesized that by counteracting the nociceptive component of this system, the magnitude and duration of the response to VS would be augmented. In the present study, the NMDA receptor antagonist AP5 [10 μg injected intrathecally (IT)] significantly increased the magnitude and duration of the analgesia (measured as tail flick latency to radiant heat) produced by VS (200 g force). At several time points the analgesic effect of AP5 combined with VS was greater than the sum of the effects of AP5 and VS separately, suggesting that they act synergistically. We propose that AP5 potentiates the analgesic effect of VS by two mechanisms: (a) antagonizing the putative pain-producing action of glutamate and glycine acting jointly at the NMDA receptor, 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).