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THIS ARTICLE HAS BEEN RETRACTED: Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury
- Source :
- Journal of Neurochemistry. 105:2249-2259
- Publication Year :
- 2008
- Publisher :
- Wiley, 2008.
-
Abstract
- 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-1beta, interleukin-6, and tumor necrosis factor-alpha. 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.
- Subjects :
- Toll-like receptor
Microglia
business.industry
Central nervous system
Hyperesthesia
chemical and pharmacologic phenomena
Nerve injury
Spinal cord
Biochemistry
Cellular and Molecular Neuroscience
medicine.anatomical_structure
Peripheral nerve injury
medicine
Neuroglia
medicine.symptom
business
Neuroscience
Subjects
Details
- ISSN :
- 00223042
- Volume :
- 105
- Database :
- OpenAIRE
- Journal :
- Journal of Neurochemistry
- Accession number :
- edsair.doi...........f6f39cd4de02859d2f5966944b75667c