Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
J Neurosci Res. 2010 Oct;88(13):2899-910. doi: 10.1002/jnr.22439.
Tetanic stimulation of the sciatic nerve (TSS) produces long-lasting pain hypersensitivity in rats. Long-term potentiation (LTP) of C- and A-fiber-evoked field potentials in the spinal cord has been explored as contributing to central sensitization in pain pathways. However, the peripheral mechanism underlying TSS-induced pain hypersensitivity remains largely unknown. We investigated the effect of TSS on peripheral nerve and the expression of activating transcription factor 3 (ATF3) in dorsal root ganglion (DRG) as a marker of neuronal injury. TSS induced a mechanical allodynia for at least 35 days and induced ATF3 expression in the ipsilateral DRG. ATF3 is colocalized with NF200-labeled myelinated DRG neurons or CGRP- and IB4-labeled unmyelinated ones. Furthermore, we found that TSS induced Wallerian degeneration of sciatic nerve at the level of myelinisation by S100 protein (to label Schwann cells) immunohistochemistry, luxol fast blue staining, and electron microscopy. TSS also elicited the activation of satellite glial cells (SGCs) and enhanced the colocalization of GFAP and P2X7 receptors. Repeated local treatment with tetrodotoxin decreased GFAP expression in SGCs and behavioral allodynia induced by TSS. Furthermore, reactive microglia and astrocytes were found in the spinal dorsal horn after TSS. These results suggest that TSS-induced nerve injury and glial activation in the DRG and spinal dorsal horn may be involved in cellular mechanisms underlying the development of persistent pain after TSS and that TSS-induced nerve injury may be used as a novel neuropathic pain model.
坐骨神经强直性刺激（TSS）可在大鼠中产生持久的痛觉过敏。脊髓中 C 和 A 纤维诱发的场电位的长时程增强（LTP）已被探索作为疼痛途径中中枢敏化的贡献因素。然而，TSS 诱导的痛觉过敏的外周机制在很大程度上仍不清楚。我们研究了 TSS 对周围神经和背根神经节（DRG）中激活转录因子 3（ATF3）表达的影响，ATF3 作为神经元损伤的标志物。TSS 至少引起 35 天的机械性痛觉过敏，并诱导同侧 DRG 中 ATF3 的表达。ATF3 与 NF200 标记的有髓 DRG 神经元或 CGRP 和 IB4 标记的无髓 DRG 神经元共定位。此外，我们发现 TSS 通过 S100 蛋白（标记施万细胞）免疫组织化学、卢索快速蓝染色和电子显微镜诱导坐骨神经在髓鞘化水平的沃勒变性。TSS 还引起卫星胶质细胞（SGC）的激活，并增强 GFAP 和 P2X7 受体的共定位。重复局部给予河豚毒素可减少 TSS 引起的 SGC 中 GFAP 表达和行为性痛觉过敏。此外，在 TSS 后还发现脊髓背角中存在反应性小胶质细胞和星形胶质细胞。这些结果表明，TSS 诱导的 DRG 和脊髓背角中的神经损伤和神经胶质激活可能参与 TSS 后持续疼痛发展的细胞机制，并且 TSS 诱导的神经损伤可用作新型神经病理性疼痛模型。
