Guan Xiaofei, Zhu Yanjie, Zhong Jian, Hollis Edmund
Burke Neurological Institute, White Plains, New York 10605.
Burke Neurological Institute, White Plains, New York 10605
J Neurosci. 2025 Jul 16;45(29):e1264242025. doi: 10.1523/JNEUROSCI.1264-24.2025.
Chronic neuropathic pain is a persistent and debilitating outcome of traumatic central nervous system injury, affecting up to 80% of individuals. Postinjury pain is refractory to treatments due to the limited understanding of the brain-spinal cord circuits that underlie pain signal processing. The corticospinal tract (CST) plays critical roles in sensory modulation during skilled movements and tactile sensation; however, a direct role for the CST in injury-associated neuropathic pain is unclear. Here we show that complete, selective CST transection at the medullary pyramids leads to hyperexcitability within lumbar deep dorsal horn and hindlimb allodynia-like behavior in chronically injured adult male and female mice. Chemogenetic regulation of CST-targeted lumbar spinal interneurons demonstrates that dysregulation of activity in this circuit underlies the development of tactile allodynia in chronic injury. Our findings shed light on an unrecognized circuit mechanism implicated in CNS injury-induced neuropathic pain and provide a novel target for therapeutic intervention.
慢性神经性疼痛是创伤性中枢神经系统损伤的一种持续且使人衰弱的后果，影响多达80%的个体。由于对疼痛信号处理背后的脑脊髓回路了解有限，损伤后疼痛难以治疗。皮质脊髓束（CST）在熟练运动和触觉感觉的感觉调节中起关键作用；然而，CST在损伤相关神经性疼痛中的直接作用尚不清楚。在这里，我们表明，在成年雄性和雌性慢性损伤小鼠的延髓锥体处完全、选择性地切断CST会导致腰深部背角的兴奋性过高以及后肢出现类似痛觉过敏的行为。对靶向CST的腰段脊髓中间神经元进行化学遗传学调控表明，该回路中活动的失调是慢性损伤中触觉痛觉过敏发展的基础。我们的研究结果揭示了一种与中枢神经系统损伤诱导的神经性疼痛相关的未被认识的回路机制，并为治疗干预提供了一个新的靶点。
