Zhang Ting, Qi Le, Sun Kai, Huan Xiang, Zhang Hao, Wang Liwei
Department of Anesthesiology and Pain Clinic, Xuzhou Central Hospital, Xuzhou, Jiangsu, China.
Department of Pain Medicine, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Mol Pain. 2025 Jan-Dec;21:17448069251333928. doi: 10.1177/17448069251333928. Epub 2025 Mar 28.
Neuropathic pain is still a clinical challenge. Inflammatory responses and autophagy in the spinal cord are important mechanisms for the occurrence and maintain of neuropathic pain. PDCD4 is an important molecule that regulates inflammation and autophagy. However, the regulatory role of PDCD4 is unknown in pain modulation. In this study we found that the expression of PDCD4 in the spinal cord of CCI mice was increased. Inhibition of PDCD4 by intrathecal injection of adeno-associated virus alleviated neuropathic pain hypersensitivity and enhanced autophagy in CCI mice, and inhibited the activation of MAPKs, as well as the expression of inflammatory factors. Intrathecal injection of autophagy inhibitor 3-MA reversed PDCD4 inhibition induced pain relief and change of autophagy. Our results indicate that spinal cord inhibition of PDCD4 alleviates pain sensitization in neuropathic pain mice through MAPKs and autophagy, and PDCD4 may be developed into a therapeutic target of neuropathic pain treatment.
神经性疼痛仍然是一个临床挑战。脊髓中的炎症反应和自噬是神经性疼痛发生和维持的重要机制。PDCD4是一种调节炎症和自噬的重要分子。然而，PDCD4在疼痛调节中的作用尚不清楚。在本研究中，我们发现CCI小鼠脊髓中PDCD4的表达增加。通过鞘内注射腺相关病毒抑制PDCD4可减轻CCI小鼠的神经性疼痛超敏反应并增强自噬，抑制MAPKs的激活以及炎症因子的表达。鞘内注射自噬抑制剂3-MA可逆转PDCD4抑制诱导的疼痛缓解和自噬变化。我们的结果表明，脊髓中PDCD4的抑制通过MAPKs和自噬减轻神经性疼痛小鼠的疼痛敏化，并且PDCD4可能发展成为神经性疼痛治疗的一个治疗靶点。
