Su Po-Yi Paul, He Liangliang, Zhang Lingyi, Yu Jessica, Guan Zhonghui
Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA, United States.
Department of Pain Management, Xuanwu Hospital, Capital Medical University, Xicheng District, Beijing, China.
Pain. 2025 Aug 4. doi: 10.1097/j.pain.0000000000003722.
Clinical neuropathic pain is typically characterized by pain arising from damage or disease affecting the somatosensory system without motor deficits. However, traditional nerve injury-induced neuropathic pain models involve damage to mixed motor-sensory nerves, complicating the assessment of pain behaviors because of motor impairments and limiting their translational relevance to clinical neuropathic pain. To overcome these limitations, we developed the saphenous-sural nerve injury model (SS model), which exclusively targets sensory nerves while sparing motor function. In this model, C57Bl/6 mice underwent ligation and transection of the saphenous and sural nerves, which are pure sensory nerves without motor fibers, resulting in rapid and persistent mechanical hypersensitivity without thermal or cold hypersensitivity. Conditioned place preference testing indicated the presence of ongoing spontaneous pain. Importantly, motor function remained unaffected, with no deficits observed in rotarod performance, paw posture, or foot drop. Cellular analyses confirmed injury-specific ATF3 expression in dorsal root ganglion sensory neurons, accompanied by significant microgliosis and astrogliosis in the ipsilateral spinal dorsal horn. In contrast to traditional models, no ATF3 expression or gliosis was observed in motor neurons or the spinal ventral horn, further reinforcing the model's sensory-specific nature. Thus, the SS model effectively replicates key features of neuropathic pain while eliminating motor confounds, enhancing its translational relevance. Its selective sensory neuron injury and robust glial activation provide a valuable platform for investigating pain mechanisms and evaluating novel therapies.
临床神经性疼痛的典型特征是由影响躯体感觉系统的损伤或疾病引起的疼痛，且无运动功能障碍。然而，传统的神经损伤诱导的神经性疼痛模型涉及混合运动感觉神经的损伤，由于运动障碍，使得疼痛行为的评估变得复杂，并限制了它们与临床神经性疼痛的转化相关性。为了克服这些局限性，我们开发了隐神经 - 腓肠神经损伤模型（SS模型），该模型专门针对感觉神经，同时保留运动功能。在这个模型中，C57Bl/6小鼠接受了隐神经和腓肠神经的结扎和横断，这两条神经是没有运动纤维的纯感觉神经，导致快速且持续的机械性超敏反应，而没有热或冷超敏反应。条件性位置偏好测试表明存在持续的自发性疼痛。重要的是，运动功能未受影响，在转棒试验、爪姿势或足下垂方面未观察到缺陷。细胞分析证实背根神经节感觉神经元中存在损伤特异性的ATF3表达，同时同侧脊髓背角有明显的小胶质细胞增生和星形胶质细胞增生。与传统模型不同，在运动神经元或脊髓腹角未观察到ATF3表达或胶质细胞增生，进一步强化了该模型的感觉特异性。因此，SS模型有效地复制了神经性疼痛的关键特征，同时消除了运动干扰，增强了其转化相关性。其选择性感觉神经元损伤和强大的胶质细胞激活为研究疼痛机制和评估新疗法提供了一个有价值的平台。
