Liu Chang-Ning, Wall Patrick D, Ben-Dor Efrat, Michaelis Martin, Amir Ron, Devor Marshall
Department of Cell and Animal Biology, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel Department of Physiology, Medical School, St. Thomas', London, UK Physiologisches Institut, Christian-Albrechts Universitat, 24098 Kiel, Germany.
Pain. 2000 Apr;85(3):503-521. doi: 10.1016/S0304-3959(00)00251-7.
We examined the relation between ectopic afferent firing and tactile allodynia in the Chung model of neuropathic pain. Transection of the L5 spinal nerve in rats triggered a sharp, four- to six-fold increase in the spontaneous ectopic discharge recorded in vivo in sensory axons in the ipsilateral L5 dorsal root (DR). The increase, which was not yet apparent 16 h postoperatively, was complete by 24 h. This indicates rapid modification of the electrical properties of the neurons. Only A-neurons, primarily rapidly conducting A-neurons, contributed to the discharge. No spontaneously active C-neurons were encountered. Tactile allodynia in hindlimb skin emerged during precisely the same time window after spinal nerve section as the ectopia, suggesting that ectopic activity in injured myelinated afferents can trigger central sensitization, the mechanism believed to be responsible for tactile allodynia in the Chung model. Most of the spike activity originated in the somata of axotomized DRG neurons; the spinal nerve end neuroma accounted for only a quarter of the overall ectopic barrage. Intracellular recordings from afferent neuron somata in excised DRGs in vitro revealed changes in excitability that closely paralleled those seen in the DR axon recordings in vivo. Corresponding changes in biophysical characteristics of the axotomized neurons were catalogued. Axotomy carried out at a distance from the DRG, in the mid-portion of the sciatic nerve, also triggered increased afferent excitability. However, this increase occurred at a later time following axotomy, and the relative contribution of DRG neuronal somata, as opposed to neuroma endings, was smaller. Axotomy triggers a wide variety of changes in the neurochemistry and physiology of primary afferent neurons. Investigators studying DRG neurons in culture need to be alert to the rapidity with which axotomy, an inevitable consequence of DRG excision and dissociation, alters key properties of these neurons. Our identification of a specific population of neurons whose firing properties change suddenly and synchronously following axotomy, and whose activity is associated with tactile allodynia, provides a powerful vehicle for defining the specific cascade of cellular and molecular events that underlie neuropathic pain.
我们在神经性疼痛的Chung模型中研究了异位传入放电与触觉异常性疼痛之间的关系。切断大鼠的L5脊神经会引发同侧L5背根（DR）感觉轴突在体记录的自发性异位放电急剧增加4至6倍。这种增加在术后16小时尚不明显，到24小时时完全显现。这表明神经元的电特性发生了快速改变。只有A神经元，主要是快速传导的A神经元，参与了放电。未发现自发活动的C神经元。后肢皮肤的触觉异常性疼痛在脊神经切断后的同一时间窗内出现，与异位放电同时发生，这表明受损有髓传入纤维中的异位活动可触发中枢敏化，而中枢敏化被认为是Chung模型中触觉异常性疼痛的发病机制。大多数锋电位活动起源于轴突切断的背根神经节（DRG）神经元的胞体；脊神经终末神经瘤仅占总体异位电活动的四分之一。在体外对分离的DRG中传入神经元胞体进行的细胞内记录显示，兴奋性变化与在体DR轴突记录中观察到的变化密切平行。对轴突切断神经元的生物物理特性的相应变化进行了分类。在坐骨神经中部远离DRG处进行轴突切断，也会引发传入兴奋性增加。然而，这种增加在轴突切断后的较晚时间出现，并且与神经瘤末梢相比，DRG神经元胞体的相对贡献较小。轴突切断会引发初级传入神经元神经化学和生理学的多种变化。研究培养中的DRG神经元的研究人员需要警惕轴突切断（DRG切除和解离的必然结果）对这些神经元关键特性的快速改变。我们鉴定出了一群特定的神经元，其放电特性在轴突切断后突然且同步改变，并且其活动与触觉异常性疼痛相关，这为确定构成神经性疼痛基础的特定细胞和分子事件级联提供了有力工具。
