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

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 neuropath...

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Detalles Bibliográficos
Autores principales: Wu, Fei-xiang, Bian, Jin-jun, Miao, Xue-rong, Huang, Sheng-dong, Xu, Xue-wu, Gong, De-jun, Sun, Yu-ming, Lu, Zhi-jie, Yu, Wei-feng
Formato: Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920570/
https://www.ncbi.nlm.nih.gov/pubmed/20714435
Descripción
Sumario: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.