THIS ARTICLE HAS BEEN RETRACTED: Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury
Version of Record online: 17 MAR 2008
© 2008 The Authors. Journal Compilation © 2008 International Society for Neurochemistry
Journal of Neurochemistry
Volume 105, Issue 6, pages 2249–2259, June 2008
How to Cite
Obata, K., Katsura, H., Miyoshi, K., Kondo, T., Yamanaka, H., Kobayashi, K., Dai, Y., Fukuoka, T., Akira, S. and Noguchi, K. (2008), THIS ARTICLE HAS BEEN RETRACTED: Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury. Journal of Neurochemistry, 105: 2249–2259. doi: 10.1111/j.1471-4159.2008.05353.x
- Issue online: 17 MAR 2008
- Version of Record online: 17 MAR 2008
- Received January 20, 2008; revised manuscript received February 14, 2008; accepted March 8, 2008.
Vol. 121, Issue 4, 693, Version of Record online: 16 MAR 2012
- mitogen-activated protein kinase;
- neuropathic pain;
- Toll-like receptor
Toll-like receptors (TLRs) play an essential role in innate immune responses and in the initiation of adaptive immune responses. Microglia, the resident innate immune cells in the CNS, express TLRs. In this study, we show that TLR3 is crucial for spinal cord glial activation and tactile allodynia after peripheral nerve injury. Intrathecal administration of TLR3 antisense oligodeoxynucleotide suppressed nerve injury-induced tactile allodynia, and decreased the phosphorylation of p38 mitogen-activated protein kinase, but not extracellular signal-regulated protein kinases 1/2, in spinal glial cells. Antisense knockdown of TLR3 also attenuated the activation of spinal microglia, but not astrocytes, caused by nerve injury. Furthermore, down-regulation of TLR3 inhibited nerve injury-induced up-regulation of spinal pro-inflammatory cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. Conversely, intrathecal injection of the TLR3 agonist polyinosine–polycytidylic acid induced behavioral, morphological, and biochemical changes similar to those observed after nerve injury. Indeed, TLR3-deficient mice did not develop tactile allodynia after nerve injury or polyinosine–polycytidylic acid injection. Our results indicate that TLR3 has a substantial role in the activation of spinal glial cells and the development of tactile allodynia after nerve injury. Thus, blocking TLR3 in the spinal glial cells might provide a fruitful strategy for treating neuropathic pain.