4 February 2012

ISSN 1449-1907

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International Journal of Biological Sciences

Journal of Cancer

Theranostics

Journal of Genomics

Int J Med Sci 2010; 7(5):251-259. doi:10.7150/ijms.7.251

Research Paper

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

Fei-xiang Wu¹, Jin-jun Bian², Xue-rong Miao¹, Sheng-dong Huang³, Xue-wu Xu¹, De-jun Gong³, Yu-ming Sun¹, Zhi-jie Lu¹, Wei-feng Yu^{1 ✉}

1. Department of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, China
2. Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
3. Institute of Thoracic Cardiac Surgery, Changhai Hospital, PLA, Shanghai 200433, China

Abstract

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-κB p65 and production of proinflammatory cytokines (e.g., TNF-α and IL-1β). 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.

Keywords: Toll-like receptor 4, neuropathic pain, NF-κB, RNA interference, IL-1β, TNF-α.