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

Authors: Wu, FX  Bian, JJ  Miao, XR  Huang, SD  Xu, XW  Gong, DJ  Sun, YM  Lu, ZJ  Yu, WF 
Citation: Wu FX, etal., Int J Med Sci. 2010 Aug 2;7(5):251-9.
Pubmed: (View Article at PubMed) PMID:20714435

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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RGD Object Information
RGD ID: 4144070
Created: 2010-09-30
Species: All species
Last Modified: 2010-09-30
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.