Muscarinic-mediated analgesia
Muscarinic-mediated analgesia
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DOI：
10.1016/s0024-3205(98)00600-6
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发表时间：
1999-01-08
期刊：
影响因子：
6.1
通讯作者：
Eisenach, JC
中科院分区：
文献类型：
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作者：
Eisenach, JC
长期以来，通过血脑屏障全身应用胆碱酯酶抑制剂可以产生镇痛作用，并增强阿片类药物的镇痛作用。胆碱能药物的一个主要止痛部位是脊髓。M受体集中在脊髓背角的浅层，这是一个伤害性感觉处理的区域，这些受体反映了主要来自胆碱能神经元的神经支配，细胞体位于背角颈部深处。脊髓注射胆碱能激动剂可产生镇痛作用，这主要反映了毒碱能受体的激活。止痛作用发生在急性伤害性刺激和慢性过敏性疼痛的动物模型中。虽然没有胆碱能激动剂在人类身上进行安全性测试，但胆碱酯酶抑制剂新斯的明已经进行了这样的测试，并对实验性疼痛、急性术后疼痛和慢性疼痛产生止痛作用。因此，毒扁豆碱胆碱能激动剂和胆碱酯酶抑制剂有望成为治疗中重度急性和慢性疼痛的非阿片类药物。
Systemic administration of cholinesterase inhibitors which cross the blood brain barrier have long been known to produce analgesia and enhance analgesia from opiates. A major site of analgesic action of cholinergic agents is the spinal cord. Muscarinic receptors are concentrated in the superficial layers of the dorsal horn of the spinal cord, an area of noxious sensory processing, and these reflect innervation primarily from cholinergic neurons with cell bodies deep in the neck of the dorsal horn. Spinal injection of cholinergic agonists results in analgesia which primarily reflects muscarinic receptor activation. Analgesia occurs in animal models of acute noxious stimulation and of chronic hypersensitivity pain. Although no cholinergic agonists have been tested for safety in humans, the cholinesterase inhibitor, neostigmine, has undergone such testing, and produces analgesia to experimental, acute postoperative, and chronic pain. Thus, muscarinic cholinergic agonists and cholinesterase inhibitors hold promise as non-opiate agents for the treatment of moderate to severe acute and chronic pain.