Spinal cord injury leads to hyperexcitability and dysfunction in spinal sensory processing. As hyperexcitable circuits can become epileptiform, we explored whether such activity emerges in a thoracic spinal cord injury (SCI) contusion model of neuropathic pain. Recordings from spinal sensory axons in multiple below-lesion segmental dorsal roots demonstrated that SCI facilitated the emergence of spontaneous ectopic burst spiking in afferent axons, which were correlated across multiple adjacent dorsal roots. Burst frequency correlated with behavioral mechanosensitivity. The same bursting events were recruited by afferent stimulation, and timing interactions with ongoing spontaneous bursts revealed that recruitment was limited by a prolonged post-burst refractory period. Ectopic bursting in afferent axons was driven by GABAA receptor activation, presumably by conversion of subthreshold GABAergic interneuronal presynaptic axoaxonic inhibitory actions to suprathreshold spiking. Collectively, the emergence of stereotyped bursting circuitry with hypersynchrony, sensory input activation, post-burst refractory period, and reorganization of connectivity represent defining features of an epileptiform network. Indeed, these same features were reproduced in naive animals with the convulsant 4-aminopyridine (fampridine). We conclude that spinal cord injury promotes the emergence of epileptiform activity in spinal sensory networks that promote profound corruption of sensory signaling. This includes hyperexcitability and bursting by ectopic spiking in afferent axons that propagate bidirectionally by reentrant central and peripheral projections as well as sensory circuit hypoexcitability during the burst refractory period. More broadly, the work links circuit hyperexcitability to epileptiform circuit emergence, further strengthening it as a conceptual basis to understand features of sensory dysfunction and neuropathic pain.

中文翻译：

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脊髓感觉回路中的紧急癫痫样活动驱动脊髓损伤后传入轴突的异位破裂和感觉功能障碍。


脊髓损伤导致脊髓感觉处理过度兴奋和功能障碍。由于过度兴奋的回路可以变成癫痫样，我们探讨了这种活动是否出现在神经性疼痛的胸脊髓损伤 （SCI） 挫伤模型中。来自多个病变下方节段背根的脊髓感觉轴突的记录表明，SCI 促进了传入轴突中自发性异位爆发尖峰的出现，这些尖峰在多个相邻的背根中相关。爆发频率与行为机械敏感性相关。通过传入刺激募集相同的爆发事件，并且与正在进行的自发爆发的时间相互作用表明募集受到爆发后不应期延长的限制。传入轴突的异位爆发是由 GABAA 受体激活驱动的，可能是通过将亚阈值 GABA 能神经元间突触前轴突抑制作用转化为超阈值尖峰。总的来说，具有超同步性的刻板爆发回路的出现、感觉输入激活、爆发后不应期和连接的重组代表了癫痫样网络的定义特征。事实上，这些相同的特征在具有惊厥 4-氨基吡啶 （fampridine） 的幼稚动物中被复制。我们得出结论，脊髓损伤促进了脊髓感觉网络中癫痫样活动的出现，从而促进了感觉信号的深刻腐败。这包括通过折返中枢和外周投射双向传播的传入轴突异位尖峰引起的过度兴奋和爆发，以及爆发不应期的感觉回路低兴奋。 更广泛地说，这项工作将回路过度兴奋与癫痫样回路出现联系起来，进一步加强了它作为理解感觉功能障碍和神经性疼痛特征的概念基础。