Walters Edgar T
Department of Integrative Biology and Pharmacology, University of Texas Medical School at Houston Houston, TX, USA.
Front Physiol. 2012 Aug 2;3:309. doi: 10.3389/fphys.2012.00309. eCollection 2012.
Spinal cord injury (SCI) causes chronic peripheral sensitization of nociceptors and persistent generation of spontaneous action potentials (SA) in peripheral branches and the somata of hyperexcitable nociceptors within dorsal root ganglia (DRG). Here it is proposed that SCI triggers in numerous nociceptors a persistent hyperfunctional state (peripheral, synaptic, and somal) that originally evolved as an adaptive response to compensate for loss of sensory terminals after severe but survivable peripheral injury. In this hypothesis, nociceptor somata monitor the status of their own receptive field and the rest of the body by integrating signals received by their peripheral and central branches and the soma itself. A nociceptor switches into a potentially permanent hyperfunctional state when central neural, glial, and inflammatory signal combinations are detected that indicate extensive peripheral injury. Similar signal combinations are produced by SCI and disseminated widely to uninjured as well as injured nociceptors. This paper focuses on the uninjured nociceptors that are altered by SCI. Enhanced activity generated in below-level nociceptors promotes below-level central sensitization, somatic and autonomic hyperreflexia, and visceral dysfunction. If sufficient ascending fibers survive, enhanced activity in below-level nociceptors contributes to below-level pain. Nociceptor activity generated above the injury level contributes to at- and above-level sensitization and pain (evoked and spontaneous). Thus, SCI triggers a potent nociceptor state that may have been adaptive (from an evolutionary perspective) after severe peripheral injury but is maladaptive after SCI. Evidence that hyperfunctional nociceptors make large contributions to behavioral hypersensitivity after SCI suggests that nociceptor-specific ion channels required for nociceptor SA and hypersensitivity offer promising targets for treating chronic pain and hyperreflexia after SCI.
脊髓损伤（SCI）会导致伤害感受器的慢性外周敏化，并在背根神经节（DRG）内的外周分支和超兴奋性伤害感受器的胞体中持续产生自发放电动作电位（SA）。本文提出，SCI在众多伤害感受器中引发一种持续的功能亢进状态（外周、突触和胞体水平），这种状态最初是作为一种适应性反应而进化出来的，以补偿严重但可存活的外周损伤后感觉末梢的丧失。在这一假说中，伤害感受器胞体通过整合其外周和中枢分支以及胞体自身接收到的信号，来监测其自身感受野和身体其他部位的状态。当检测到指示广泛外周损伤的中枢神经、胶质细胞和炎症信号组合时，伤害感受器会转变为潜在的永久性功能亢进状态。SCI会产生类似的信号组合，并广泛传播到未受伤以及受伤的伤害感受器。本文重点关注因SCI而发生改变的未受伤伤害感受器。损伤平面以下的伤害感受器产生的增强活动会促进损伤平面以下的中枢敏化、躯体和自主神经反射亢进以及内脏功能障碍。如果有足够的上行纤维存活，损伤平面以下的伤害感受器增强的活动会导致损伤平面以下的疼痛。损伤平面以上产生的伤害感受器活动会导致损伤平面及以上的敏化和疼痛（诱发痛和自发痛）。因此，SCI引发了一种强大的伤害感受器状态，这种状态在严重外周损伤后可能是适应性的（从进化角度来看），但在SCI后是适应不良的。有证据表明，功能亢进的伤害感受器对SCI后的行为超敏反应有很大贡献，这表明伤害感受器SA和超敏反应所需的伤害感受器特异性离子通道为治疗SCI后的慢性疼痛和反射亢进提供了有前景的靶点。
