Pain Research Center and Department of Physiology, Zhongshan Medical School of Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, PR China; Department of Anesthesiology, Cancer Center, Sun Yat-Sen University, State Key Laboratory of Oncology in South China, Collaborative, Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, PR China.
Pain Research Center and Department of Physiology, Zhongshan Medical School of Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, PR China; Department of Pathology, The Red Cross Hospital of Yulin, 1 Jinwang Rd, Yulin 537000, PR China.
Neuroscience. 2018 Apr 15;376:142-151. doi: 10.1016/j.neuroscience.2018.02.023. Epub 2018 Feb 23.
Both calpain-2 (CALP2) and tumor necrosis factor-α (TNF-α) contribute to persistent bilateral hypersensitivity in animals subjected to L5 ventral root transection (L5-VRT), a model of selective motor fiber injury without sensory nerve damage. However, specific upstream mechanisms regulating TNF-α overexpression and possible relationships linking CALP2 and TNF-α have not yet been investigated in this model. We examined changes in CALP2 and TNF-α protein levels and alterations in bilateral mechanical threshold within 24 h following L5-VRT model injury. We observed robust elevation of CALP2 and TNF-α in bilateral dorsal root ganglias (DRGs) and bilateral spinal cord neurons. CALP2 and TNF-α protein induction by L5-VRT were significantly inhibited by pretreatment using the calpain inhibitor MDL28170. Administration of CALP2 to rats without nerve injury further supported a role of CALP2 in the regulation of TNF-α expression. Although clinical trials of calpain inhibition therapy for alleviation of neuropathic pain induced by motor nerve injury have not yet shown success, our observations linking CALP2 and TNF-α provide a framework of a systems' approach based perspective for treating neuropathic pain.
钙蛋白酶-2（CALP2）和肿瘤坏死因子-α（TNF-α）均有助于接受 L5 腹根横断术（L5-VRT）的动物持续出现双侧过敏反应，L5-VRT 是一种选择性运动纤维损伤而无感觉神经损伤的模型。然而，在该模型中，尚未研究调节 TNF-α过表达的特定上游机制以及可能将 CALP2 和 TNF-α 联系起来的机制。我们检查了 L5-VRT 模型损伤后 24 小时内 CALP2 和 TNF-α 蛋白水平的变化以及双侧机械阈值的改变。我们观察到双侧背根神经节（DRG）和双侧脊髓神经元中 CALP2 和 TNF-α 的蛋白水平显著升高。CALP2 抑制剂 MDL28170 的预处理显著抑制了 L5-VRT 诱导的 CALP2 和 TNF-α 的蛋白诱导。在没有神经损伤的大鼠中给予 CALP2 进一步支持了 CALP2 在调节 TNF-α表达中的作用。尽管针对运动神经损伤引起的神经病理性疼痛的钙蛋白酶抑制治疗的临床试验尚未取得成功，但我们将 CALP2 和 TNF-α 联系起来的观察结果为治疗神经病理性疼痛提供了一种基于系统方法的框架。
