Cellular mechanisms of neuropathic pain, morphine tolerance, and their interactions
Cellular mechanisms of neuropathic pain, morphine tolerance, and their interactions
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DOI：
10.1073/pnas.96.14.7731
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发表时间：
1999-07-06
影响因子：
11.1
通讯作者：
Price, DD
中科院分区：
文献类型：
--
作者：
Mayer, DJ;Mao, JR;Price, DD
在过去的几年里，我们的实验室以及其他实验室积累了令人信服的证据，表明脊髓内神经元可塑性变化引起的中枢过度活动状态在与神经损伤和炎症相关的痛觉过敏中发挥着关键作用。在我们的实验室中，作为神经病理性疼痛的大鼠模型，坐骨神经慢性压迫损伤导致中枢神经系统兴奋性氨基酸受体的激活，以及随后的细胞内级联反应，包括蛋白激酶C的移位和激活，一氧化氮的产生，以及一氧化氮激活的多(ADP核糖)合成酶的激活，类似的细胞机制也参与了对吗啡镇痛效应的耐受。最近观察到的一个现象是“暗神经元”的发展，它与慢性压迫性损伤和吗啡耐受有关，与痛觉过敏和吗啡耐受有关的一个作用部位在脊髓背角的浅层。这些观察表明，痛敏和吗啡耐受可能通过共同的神经底物在兴奋性氨基酸受体激活和随后的细胞内事件水平上相互作用，在背角浅层水平上相互关联。痛敏和吗啡耐受神经机制之间的相互关系的论证可能有助于更好地理解这两种现象的神经生物学，特别是疼痛。这一知识也可能为使用阿片类镇痛剂改善疼痛管理提供科学依据。
Compelling evidence has accumulated over the last several years from our laboratory, as well as others, indicating that central hyperactive states resulting from neuronal plastic changes within the spinal cord play a critical role in hyperalgesia associated with nerve injury and inflammation. In our laboratory, chronic constriction injury of the common sciatic nerve, a rat model of neuropathic pain, has been shown to result in activation of central nervous system excitatory amino acid receptors and subsequent intracellular cascades including protein kinase C translocation and activation, nitric oxide production, and nitric oxide-activated poly(ADP ribose) synthetase activation, Similar cellular mechanisms also have been implicated in the development of tolerance to the analgesic effects of morphine. A recently observed phenomenon, the development of "dark neurons," is associated with both chronic constriction injury and morphine tolerance, A site of action involved in both hyperalgesia and morphine tolerance is in the superficial laminae of the spinal cord dorsal horn. These observations suggest that hyperalgesia and morphine tolerance may be interrelated at the level of the superficial laminae of the dorsal horn by common neural substrates that interact at the level of excitatory amino acid receptor activation and subsequent intracellular events, The demonstration of interrelationships between neural mechanisms underlying hyperalgesia and morphine tolerance may lead to a better understanding of the neurobiology of these two phenomena in particular and pain in general. This knowledge may also provide a scientific basis for improved pain management with opiate analgesics.