鞘内注射 Toll 样受体 4 的 siRNA 可减少神经病理性疼痛大鼠模型的痛觉过敏。

Intrathecal siRNA against Toll-like receptor 4 reduces nociception in a rat model of neuropathic pain.

机构信息

Department of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, China.

出版信息

Int J Med Sci. 2010 Aug 2;7(5):251-9. doi: 10.7150/ijms.7.251.

BACKGROUND

Neuropathic pain is characterized by hyperalgesia, allodynia and spontaneous pain. It often occurs as a result of injury to peripheral nerves, dorsal root ganglions (DRG), spinal cord, or brain. Recent studies have suggested that Toll-like receptor 4 (TLR4) might play a role in neuropathic pain.

METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the role of TLR4 in a rat chronic constriction injury (CCI) model and explored the feasibility of treating neuropathic pain by inhibiting TLR4. Our results demonstrated that intrathecal siRNA-mediated suppression of TLR4 attenuated CCI-induced mechanical allodynia and thermal hyperalgesia through inhibiting the activation of NF-kappaB p65 and production of proinflammatory cytokines (e.g., TNF-alpha and IL-1 beta).

CONCLUSIONS/SIGNIFICANCE: These findings suggest that suppression of TLR4 mediated by intrathecally administered siRNA may be a new strategy for the treatment of neuropathic pain.

背景

神经病理性疼痛的特点是痛觉过敏、感觉异常和自发性疼痛。它通常是由于外周神经、背根神经节（DRG）、脊髓或大脑损伤引起的。最近的研究表明，Toll 样受体 4（TLR4）可能在神经病理性疼痛中发挥作用。

方法/主要发现：在这项研究中，我们研究了 TLR4 在大鼠慢性缩窄性损伤（CCI）模型中的作用，并探讨了通过抑制 TLR4 治疗神经病理性疼痛的可行性。结果表明，鞘内 siRNA 介导的 TLR4 抑制通过抑制 NF-κB p65 的激活和促炎细胞因子（如 TNF-α和 IL-1β）的产生，减轻 CCI 诱导的机械性感觉异常和热痛觉过敏。

结论/意义：这些发现表明，鞘内给予 siRNA 抑制 TLR4 可能是治疗神经病理性疼痛的一种新策略。