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


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.

SUBMITTER: Wu FX 

PROVIDER: S-EPMC2920570 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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

Wu Fei-xiang FX   Bian Jin-jun JJ   Miao Xue-rong XR   Huang Sheng-dong SD   Xu Xue-wu XW   Gong De-jun DJ   Sun Yu-ming YM   Lu Zhi-jie ZJ   Yu Wei-feng WF  

International journal of medical sciences 20100802 5


<h4>Background</h4>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.<h4>Methodology/principal findings</h4>In this study, we investigated the role of TLR4 in a rat chronic constriction injury (CCI) model and explored the feasibility of treating neuropat  ...[more]

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