Kim Y I, Na H S, Kim S H, Han H C, Yoon Y W, Sung B, Nam H J, Shin S L, Hong S K
Department of Physiology and Neuroscience Research Institute, Korea University College of Medicine, Seoul, South Korea.
Neuroscience. 1998 Sep;86(1):301-9. doi: 10.1016/s0306-4522(98)00022-0.
Recent evidence indicates that neuropathic pain from partial peripheral nerve injury is maintained by electrophysiologically abnormal signals from injured sensory neurons. To gain an insight into the mechanisms underlying this electrophysiological abnormality, we examined the effects of S1 spinal nerve transection on the membrane properties of S1 dorsal root ganglion neurons one to two weeks after injury. This injury produced significant action potential broadening [40% (1 ms) in C-, 149% (1.5 ms) in A delta- and 84% (0.5 ms) in A alpha/beta-cells], which was primarily due to the enhancement of the "shoulder" appearing on the falling phase of the action potential in C- and A delta-cells and the emergence of a shoulder in A alpha/beta-cells, and significant cell-type specific changes in the time-course of the rising phase of the action potential; i.e. an increase in rise time (A delta: 35%, 0.15 ms; A alpha/beta: 13%, 0.04 ms) and a decrease in the maximal rate of rise (A delta: 17%, 77 V/s; A alpha/beta: 13%, 79 V/s). In addition, the nerve injury led to a significant reduction of the rheobase, an index of neuronal excitability, in all types of cells (by 41% in C-, 71% in A delta- and 59% in A alpha/beta-cells). The reduction of rheobase in A-cells was associated with a concomitant increase in apparent input resistance (by 269% in A delta- and 192% in A alpha/beta-cells), which was measured near the resting membrane potential. By contrast, the rheobase reduction in C-cells was associated with a concurrent depolarizing shift (approximately 4 mV) of the resting membrane potential. The nerve injury-induced reduction of rheobase was not accompanied by related change in input resistance or threshold potential in any of the cell populations. The present results indicate that chronic peripheral axotomy of dorsal root ganglion neurons, which gives rise to neuropathic pain, produces profound changes in the action potential waveform of dorsal root ganglion neurons in a cell type-specific fashion. Furthermore, the results suggest that the axotomy increases the excitability of dorsal root ganglion neurons not by altering input resistance (i.e. leak conductance) or threshold potential, but by increasing apparent input resistance near the resting membrane potential in A-cells and decreasing the resting membrane potential in C-cells.
最近的证据表明，部分周围神经损伤所致的神经性疼痛是由受损感觉神经元发出的电生理异常信号维持的。为深入了解这种电生理异常背后的机制，我们在损伤后一至两周，研究了S1脊神经横断对S1背根神经节神经元膜特性的影响。这种损伤导致动作电位显著增宽[C类细胞增宽40%（1毫秒），Aδ类细胞增宽149%（1.5毫秒），Aα/β类细胞增宽84%（0.5毫秒）]，这主要是由于C类和Aδ类细胞动作电位下降相出现的“肩部”增强，以及Aα/β类细胞出现肩部，并且动作电位上升相的时间进程出现显著的细胞类型特异性变化；即上升时间增加（Aδ类细胞：35%，0.15毫秒；Aα/β类细胞：13%，0.04毫秒），最大上升速率降低（Aδ类细胞：17%，77伏/秒；Aα/β类细胞：13%，79伏/秒）。此外，神经损伤导致所有类型细胞的基强度（神经元兴奋性指标）显著降低（C类细胞降低41%，Aδ类细胞降低71%，Aα/β类细胞降低59%）。A类细胞基强度的降低与静息膜电位附近测量的表观输入电阻同时增加有关（Aδ类细胞增加269%，Aα/β类细胞增加192%）。相比之下，C类细胞基强度的降低与静息膜电位同时出现的去极化偏移（约4毫伏）有关。神经损伤引起的基强度降低在任何细胞群体中均未伴随输入电阻或阈电位的相关变化。目前的结果表明，导致神经性疼痛的背根神经节神经元慢性周围轴突切断术，以细胞类型特异性方式使背根神经节神经元的动作电位波形产生深刻变化。此外，结果表明轴突切断术增加背根神经节神经元兴奋性的方式不是改变输入电阻（即漏电导）或阈电位，而是通过增加A类细胞静息膜电位附近的表观输入电阻以及降低C类细胞的静息膜电位。
