Department of Neurology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230000, Anhui Province, China.
The School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, 230000, China.
J Mol Neurosci. 2024 Jul 24;74(3):73. doi: 10.1007/s12031-024-02252-0.
Low back pain (LBP) has become a leading cause of disability worldwide. Astrocyte activation in the spinal cord plays an important role in the maintenance of latent sensitization of dorsal horn neurons in LBP. However, the role of spinal c-Jun N-terminal kinase (JNK) in astrocytes in modulating pain behavior of LBP model rats and its neurobiological mechanism have not been elucidated. Here, we investigate the role of the JNK signaling pathway on hypersensitivity and anxiety-like behavior caused by repetitive nerve growth factor (NGF) injections in male non-specific LBP model rats. LBP was produced by two injections (day 0, day 5) of NGF into multifidus muscle of the low backs of rats. We observed prolonged mechanical and thermal hypersensitivity in the low backs or hindpaws. Persistent anxiety-like behavior was observed, together with astrocyte, p-JNK, and neuronal activation and upregulated expression of monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-X-C motif) ligand 1 (CXCL1) proteins in the spinal L2 segment. Second, the JNK inhibitor SP600125 was intrathecally administrated in rats from day 10 to day 12. It attenuated mechanical and thermal hypersensitivity of the low back or hindpaws and anxiety-like behavior. Meanwhile, SP600125 decreased astrocyte and neuronal activation and the expression of MCP-1 and CXCL1 proteins. These results showed that hypersensitivity and anxiety-like behavior induced by NGF in LBP rats could be attenuated by the JNK inhibitor, together with downregulation of spinal astrocyte activation, neuron activation, and inflammatory cytokines. Our results indicate that intervening with the spinal JNK signaling pathway presents an effective therapeutic approach to alleviating LBP.
下背痛（LBP）已成为全球致残的主要原因。脊髓星形胶质细胞的激活在维持 LBP 背角神经元潜伏性致敏中起重要作用。然而，脊髓 c-Jun N-末端激酶（JNK）在调节 LBP 模型大鼠疼痛行为中的作用及其神经生物学机制尚未阐明。在这里，我们研究了 JNK 信号通路在重复神经生长因子（NGF）注射引起的男性非特异性 LBP 模型大鼠过敏和焦虑样行为中的作用。LBP 通过将 NGF 两次注射（第 0 天，第 5 天）到大鼠背部多裂肌中来产生。我们观察到背部或后脚的机械和热过敏持续时间延长。观察到持续的焦虑样行为，同时伴有星形胶质细胞、p-JNK、神经元激活以及脊髓 L2 节段单核细胞趋化蛋白-1（MCP-1）和趋化因子（C-X-C 基序）配体 1（CXCL1）蛋白的上调。其次，从第 10 天到第 12 天，JNK 抑制剂 SP600125 鞘内给药。它减轻了背部或后脚的机械和热过敏以及焦虑样行为。同时，SP600125 降低了星形胶质细胞和神经元的激活以及 MCP-1 和 CXCL1 蛋白的表达。这些结果表明，NGF 在 LBP 大鼠中引起的过敏和焦虑样行为可以通过 JNK 抑制剂减轻，同时下调脊髓星形胶质细胞激活、神经元激活和炎症细胞因子。我们的结果表明，干预脊髓 JNK 信号通路是缓解 LBP 的一种有效治疗方法。
