Sawynok J
Prog Neuropsychopharmacol Biol Psychiatry. 1984;8(4-6):581-6. doi: 10.1016/0278-5846(84)90018-6.
GABAergic mechanisms appear to be involved in antinociceptive processes. Generally, peripheral administration of GABAergic agents increases the antinociceptive effect of morphine, but central administration inhibits this effect, suggesting that multiple interactions may occur. GABAergic agents also can produce antinociception directly. Muscimol and THIP (GABAA agonists) act at supraspinal sites to produce antinociception, but do not appear to interact with bicuculline sensitive receptors. Baclofen (a GABAB agonist) acts at both supraspinal and spinal sites. Supraspinal mechanisms include inhibition of ascending noradrenergic and dopaminergic pathways but activation of descending noradrenergic pathways. The spinal mechanism may involve postsynaptic inhibition of the effect of substance P. D-Baclofen is an antagonist at spinal baclofen receptors. Antinociception produced by inhibitors of GABA-transaminase is not reduced by bicuculline in most studies, while manipulations which increase the antinociceptive effect of baclofen do not alter or block the effect of GABA-transaminase inhibitors. An understanding of the role of GABAA and GABAB receptors in antinociception will require clarification of some curious pharmacological actions of bicuculline and the use of a specific GABAB receptor antagonist.
γ-氨基丁酸能机制似乎参与了抗伤害感受过程。一般来说，外周给予γ-氨基丁酸能药物会增强吗啡的抗伤害感受作用，但中枢给予则会抑制这种作用，这表明可能会发生多种相互作用。γ-氨基丁酸能药物也可直接产生抗伤害感受作用。蝇蕈醇和 THIP（γ-氨基丁酸A受体激动剂）作用于脊髓上部位产生抗伤害感受作用，但似乎不与荷包牡丹碱敏感受体相互作用。巴氯芬（一种γ-氨基丁酸B受体激动剂）作用于脊髓上和脊髓部位。脊髓上机制包括抑制去甲肾上腺素能和多巴胺能上行通路，但激活去甲肾上腺素能下行通路。脊髓机制可能涉及对P物质作用的突触后抑制。D-巴氯芬是脊髓巴氯芬受体的拮抗剂。在大多数研究中，γ-氨基丁酸转氨酶抑制剂产生的抗伤害感受作用不会被荷包牡丹碱减弱，而增强巴氯芬抗伤害感受作用的操作不会改变或阻断γ-氨基丁酸转氨酶抑制剂的作用。要了解γ-氨基丁酸A和γ-氨基丁酸B受体在抗伤害感受中的作用，需要阐明荷包牡丹碱的一些奇特药理作用，并使用特异性γ-氨基丁酸B受体拮抗剂。
