Forman L J
University of Medicine and Dentistry of New Jersey - School of Osteopathic Medicine, Department of Cell Biology, Stratford 08084, USA.
Life Sci. 1999;64(21):1877-87. doi: 10.1016/s0024-3205(99)00134-4.
Inhibition of nitric oxide synthase (NOS) activity results in opioid-mediated supraspinal analgesia in the rat, as indicated by increased reaction time in the hot plate test. It is documented that a relationship exists between NMDA receptor activation and the activity of NOS. The present investigation sought to determine if inactivation of the NMDA receptor produced antinociception of supraspinal origin, as was observed in response to inhibition of NOS, and if this response was mediated by brain opioids, by activation of receptors for the neurotransmitter, dopamine, or both. Administration of MK-801, a non-competitive antagonist of the NMDA receptor, produced significant antinociception as measured by reaction time in the hot plate test of analgesia. Antinociception resulting from treatment with MK-801 appeared to be mediated by brain opioids, as indicated by the ability of the opioid antagonist, naloxone, to partially reverse the effect of MK-801 administration. This analgesic response was also partially diminished by administration of the dopamine D1 receptor antagonist, SCH 23390 and the dopamine D2 receptor antagonist, sulpiride. The analgesia resulting from NMDA receptor antagonism was found to be only partially attributable to dopamine and brain opioids, since co-administration of naloxone and SCH 23390 or naloxone and sulpiride, were unable to completely reverse the antinociceptive response to MK-801. The present findings suggest that inhibition of NMDA receptor activity produces supraspinal analgesia. Furthermore, it appears that antinociception induced by blockade of the NMDA receptor results, at least in part, from activation of endogenous brain opioids and stimulation of D1 and D2 subtypes of the dopamine receptor.
一氧化氮合酶（NOS）活性的抑制导致大鼠体内阿片类药物介导的脊髓上镇痛，这在热板试验中反应时间增加得到了体现。有文献记载，N-甲基-D-天冬氨酸（NMDA）受体激活与NOS活性之间存在关联。本研究旨在确定NMDA受体失活是否会产生脊髓上起源的抗伤害感受，如同抑制NOS时所观察到的那样，以及这种反应是否由脑内阿片类药物介导，是否通过神经递质多巴胺的受体激活，或两者兼而有之。给予NMDA受体的非竞争性拮抗剂MK-801，在热板镇痛试验中通过反应时间测量产生了显著的抗伤害感受。MK-801治疗所产生的抗伤害感受似乎由脑内阿片类药物介导，这由阿片类拮抗剂纳洛酮部分逆转MK-801给药效果的能力所表明。多巴胺D1受体拮抗剂SCH 23390和多巴胺D2受体拮抗剂舒必利的给药也部分减弱了这种镇痛反应。发现NMDA受体拮抗所产生的镇痛仅部分归因于多巴胺和脑内阿片类药物，因为纳洛酮与SCH 23390或纳洛酮与舒必利的联合给药无法完全逆转对MK-801的抗伤害感受反应。本研究结果表明，NMDA受体活性的抑制产生脊髓上镇痛。此外，似乎NMDA受体阻断所诱导的抗伤害感受至少部分源于内源性脑内阿片类药物的激活以及多巴胺受体D1和D2亚型的刺激。
