Caba M, Komisaruk B R, Beyer C
Instituto de Investigaciones Biológicas, Universidad Veracruzana, Xalapa, Veracruz, Mexico.
Pharmacol Biochem Behav. 1998 Sep;61(1):45-8. doi: 10.1016/s0091-3057(98)00083-5.
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 microg injected intrathecally (i.t.)] 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).
阴道宫颈刺激（VS）可使多种神经递质释放到脊髓的灌流液中；这些神经递质既能刺激伤害性感受系统（例如，作用于N-甲基-D-天冬氨酸（NMDA）位点的谷氨酸和甘氨酸），也能刺激抗伤害感受系统（例如，γ-氨基丁酸（GABA）、去甲肾上腺素、5-羟色胺（5-HT）以及作用于士的宁敏感受体的甘氨酸）。虽然这两个相互对立的系统之间的平衡能够决定对VS反应的性质、程度和持续时间，但VS的典型主要反应是镇痛。我们推测，通过抵消该系统的伤害性感受成分，对VS的反应程度和持续时间将会增强。在本研究中，NMDA受体拮抗剂AP5[鞘内注射（i.t.）10微克]显著增加了VS（200克力）所产生的镇痛程度和持续时间（以对辐射热的甩尾潜伏期来衡量）。在几个时间点上，AP5与VS联合使用的镇痛效果大于AP5和VS单独使用效果之和，这表明它们具有协同作用。我们提出，AP5通过两种机制增强VS的镇痛效果：（a）拮抗谷氨酸和甘氨酸共同作用于NMDA受体时可能产生疼痛的作用，因此，（b）使VS释放的抑制性神经递质（例如，作用于士的宁敏感受体的甘氨酸和GABA）的镇痛作用得以不受阻碍地发挥。
