Lidocaine Attenuates the Development of Diabetic-Induced Tactile Allodynia by Inhibiting Microglial Activation
Lidocaine Attenuates the Development of Diabetic-Induced Tactile Allodynia by Inhibiting Microglial Activation
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DOI：
10.1213/ane.0b013e31822827a2
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发表时间：
2011-10-01
影响因子：
5.7
通讯作者：
Inada, Eiichi
中科院分区：
文献类型：
--
作者：
Suzuki, Naoko;Hasegawa-Moriyama, Maiko;Inada, Eiichi
背景：利多卡因在临床上用于糖尿病引起的神经病变相关的触觉异常性疼痛。虽然利多卡因通过抑制小胶质细胞激活的镇痛作用与损伤诱导的神经病理性疼痛的发展有关，但其在糖尿病诱导的触觉异常性疼痛中的作用机制尚未完全阐明。为了评价利多卡因对糖尿病神经病变中小胶质细胞反应的影响，注射链脲佐菌素（STZ）的小鼠接受持续输注利多卡因（媒介物，2%或10%）。在第21天，评估背角中的小胶质细胞积聚和p38丝裂原活化蛋白激酶活化。在体外，利多卡因对细胞活力，单核细胞趋化蛋白-1的趋化反应，并诱导促炎介质的影响进行了检查，在干扰素（IFN）-γ刺激的初级小胶质细胞。结果：连续全身给药利多卡因在触觉异常性疼痛的早期进展产生持久的镇痛效果STZ治疗的小鼠。利多卡因显著减少背角小胶质细胞的积聚和p38磷酸化。在体外，利多卡因下调IFN-γ诱导的诱导型氧化物合成酶和白细胞介素-1 β的基因诱导。利多卡因预处理显著降低了IFN-γ激活的小胶质细胞对单核细胞趋化蛋白-1的趋化反应。结论：利多卡因可能通过调节脊髓小胶质细胞中的p38通路而减轻STZ诱导的触觉异常性疼痛。在糖尿病引起的神经病变的早期通过利多卡因治疗来抑制小胶质细胞活化代表了触觉异常性疼痛的潜在治疗策略。（Anesth Analg 2011;113：941-6）
BACKGROUND: Lidocaine is used clinically for tactile allodynia associated with diabetes-induced neuropathy. Although the analgesic effect of lidocaine through suppression of microglial activation has been implicated in the development of injury-induced neuropathic pain, its mechanism of action in diabetes-induced tactile allodynia has not yet been completely elucidated.METHODS: To evaluate the effects of lidocaine on microglial response in diabetic neuropathy, streptozotocin (STZ)-injected mice received a continuous infusion of lidocaine (vehicle, 2%, or 10%) from day 14 to day 21 after STZ injection. On day 21, microglial accumulation and p38 mitogen-activated protein kinase activation in the dorsal horn were evaluated. In vitro, the effects of lidocaine on cell viability, chemotactic response to monocyte chemotactic protein-1, and induction of proinflammatory mediators were examined in interferon (IFN)-gamma-stimulated primary microglial cells.RESULTS: Continuous systemic administration of lidocaine in the early progression of tactile allodynia produced long-lasting analgesic effects in STZ-treated mice. Lidocaine significantly reduced accumulation and p38 phosphorylation of microglial cells in the dorsal horn. In vitro, lidocaine down-regulated IFN-gamma-induced gene induction of inducible oxide synthase and interleukin-1 beta. Pretreatment with lidocaine significantly reduced chemotactic response to monocyte chemotactic protein-1 of IFN-gamma-activated microglial cells.CONCLUSION: Lidocaine alleviates STZ-induced tactile allodynia, possibly by modulating the p38 pathway in spinal microglial cells. Inhibiting microglial activation by lidocaine treatment early in the course of diabetes-induced neuropathy represents a potential therapeutic strategy for tactile allodynia. (Anesth Analg 2011;113:941-6)