• Fei-xiang Wu, Jin-jun Bian, Xue-rong Miao, Sheng-dong Huang, Xue-wu Xu, De-jun Gong, Yu-ming Sun, Zhi-jie Lu, and Wei-feng Yu.
• Department of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, China.
• Int J Med Sci. 2010 Jan 1;7(5):251-9.

BackgroundNeuropathic 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 FindingsIn 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/SignificanceThese findings suggest that suppression of TLR4 mediated by intrathecally administered siRNA may be a new strategy for the treatment of neuropathic pain.

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