Intrathecal SiRNA Against Toll-like Receptor 4 Reduces Nociception in a Rat Model of Neuropathic Pain

Overview

Journal Int J Med Sci

Specialty General Medicine

Date 2010 Aug 18

PMID 20714435

Citations 56

Authors

Fei-Xiang Wu

Jin-Jun Bian

Xue-Rong Miao

Sheng-Dong Huang

Xue-Wu Xu

De-Jun Gong

Yu-Ming Sun

Zhi-Jie Lu

Wei-Feng Yu

Affiliations

Soon will be listed here.

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-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.

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