Causalgia, pathological pain, and adrenergic receptors.
Causalgia, pathological pain, and adrenergic receptors.
复制标题
DOI：
10.1073/pnas.96.14.7664
复制
发表时间：
1999-07
影响因子：
11.1
通讯作者：
E. Perl
中科院分区：
文献类型：
--
作者：
E. Perl
控制化学信使分子受体的表达和调节这些受体的活性现在被确定为改变细胞反应的方法。本文通过提出原发性传入神经元中α -肾上腺素能受体表达增加是经典痛症疼痛病因学的一部分的假设，将这些机制扩展到病理性疼痛领域。外周神经损伤或组织破坏引起外周伤害感受器的改变，使它们被交感神经活动和肾上腺素能物质兴奋。这种兴奋是由α -肾上腺素能受体介导的，其时间过程让人想起实验性的去神经超敏感。混合神经或交感神经节后神经供应受损后，神经元表型的改变是显而易见的。类似的部分去神经也会导致背根神经节神经元数量的大量增加，这证明了α -肾上腺素能受体的存在。该假说提出，α -肾上腺素能受体在初级传入神经元中的存在增加是由于周围神经纤维与其细胞体断开连接所产生的细胞因子/生长因子引发的基因表达改变。这些额外的肾上腺素能受体被认为使伤害感受器和其他初级传入神经元被局部或循环的去甲肾上腺素和肾上腺素兴奋。对于中枢通路，肾上腺素能兴奋将等同于有害事件产生的兴奋，并因此引起疼痛。为了支持这一观点，有证据表明，在痛症中存在一种形式的去神经超敏感，并且在交感神经活动丧失后，人类α -肾上腺素能受体的表达增加。
Control of expression of molecular receptors for chemical messengers and modulation of these receptors' activity are now established as ways to alter cellular reaction. This paper extends these mechanisms to the arena of pathological pain by presenting the hypothesis that increased expression of alpha-adrenergic receptors in primary afferent neurons is part of the etiology of pain in classical causalgia. It is argued that partial denervation by lesion of peripheral nerve or by tissue destruction induces a change in peripheral nociceptors, making them excitable by sympathetic activity and adrenergic substances. This excitation is mediated by alpha-adrenergic receptors and has a time course reminiscent of experimental denervation supersensitivity. The change in neuronal phenotype is demonstrable after lesions of mixed nerves or of the sympathetic postganglionic supply. Similar partial denervations also produce a substantial increase in the number of dorsal root ganglion neurons evidencing the presence of alpha-adrenergic receptors. The hypothesis proposes the increased presence of alpha-adrenergic receptors in primary afferent neurons to result from an altered gene expression triggered by cytokines/growth factors produced by disconnection of peripheral nerve fibers from their cell bodies. These additional adrenergic receptors are suggested to make nociceptors and other primary afferent neurons excitable by local or circulating norepinephrine and epinephrine. For central pathways, the adrenergic excitation would be equivalent to that produced by noxious events and would consequently evoke pain. In support, evidence is cited for a form of denervation supersensitivity in causalgia and for increased expression of human alpha-adrenergic receptors after loss of sympathetic activity.