Puerarin alleviate radicular pain from lumbar disc herniation by inhibiting ERK-dependent spinal microglia activation
Puerarin alleviate radicular pain from lumbar disc herniation by inhibiting ERK-dependent spinal microglia activation
复制标题
葛根素通过抑制 ERK 依赖性脊髓小胶质细胞激活减轻腰椎间盘突出症引起的根性疼痛
DOI：
10.1016/j.npep.2018.10.001
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发表时间：
2018-12-01
期刊：
影响因子：
2.9
通讯作者：
Zhao, Yuan-Shu
中科院分区：
文献类型：
--
作者：
Zhong, Yi;Huang, Yang-Liang;Zhao, Yuan-Shu
腰椎间盘突出症是神经根性疼痛的常见原因，但其机制仍不明确，治疗仍不令人满意。许多研究表明，一种中药葛根素可以缓解糖尿病和神经损伤引起的慢性疼痛。到目前为止，葛根素在神经根性疼痛中的作用和机制尚不清楚。本研究采用自体髓核植入诱导的大鼠腰椎间盘突出症模型，观察葛根素对神经根性疼痛的镇痛作用。葛根素于术前1h开始腹腔注射，每日1次，连续7d。结果表明，植入NP可引起持续疼痛，表现为同侧后足的缩足阈值(PWT)和缩足潜伏期(PWL)缩短，持续时间长达术后20d。脊髓磷酸化细胞外信号调节激酶(p-ERK)在术后第5天至第20天在同侧上调，而对侧无上调，且主要与小胶质细胞共定位。从术后第7天到第20天，葛根素降低p-ERK的表达。葛根素或ERIC抑制剂PD98059可减轻NP植入大鼠的疼痛行为，减少小胶质细胞标志物离子钙结合适配器分子1(Iba-1)的表达。结果提示，葛根素可能通过抑制ERIC依赖或伴随的脊髓小胶质细胞激活而减轻神经根性疼痛。
Lumbar disc herniation is a common cause of radicular pain, but the mechanism remains ambiguous and the treatment stays unsatisfied. Many studies revealed a traditional Chinese medicine puerarin may moderate chronic pain from diabetes and nerve injury. Thus far, the role and mechanism of puerarin in radicular pain is still unknown. In this study, by using a rat model of lumbar disc herniation, which was induced by autologous nucleus pulposus (NP) implantation, the analgesic effect of puerarin on radicular pain was tested. Puerarin was delivered intraperitoneally form 1 h before surgery, and once daily for 7 days. The results demonstrated that NP implantation induced long-lasting pain, characterized by decrease of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in ipsilateral hindpaws, as long as day 20 after surgery. Spinal phosphorylated extracellular signal-regulated kinase (p-ERK) was up-regulated from day 5 to day 20 after surgery in ipsilateral but not contralateral side, and p-ERK was mainly co-localized with microglia. Puerarin decreased p-ERK expression from day 7 to day 20 after surgery. Puerarin or ERIC inhibitor PD98059 alleviated pain behaviors, decreased expression of microglia marker ionized calcium-binding adaptor molecule 1 (Iba-1) in rats with NP implantation. The results suggested puerarin may alleviate radicular pain by inhibiting ERIC-dependent or accompanied spinal microglia activation.