title: Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury.
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.
authors: Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors: Koichi
authors: K
authors: Obata
authors: Hirokazu
authors: H
authors: Katsura
authors: Kan
authors: K
authors: Miyoshi
authors: Takashi
authors: T
authors: Kondo
authors: Hiroki
authors: H
authors: Yamanaka
authors: Kimiko
authors: K
authors: Kobayashi
authors: Yi
authors: Y
authors: Dai
authors: Tetsuo
authors: T
authors: Fukuoka
authors: Shizuo
authors: S
authors: Akira
authors: Koichi
authors: K
authors: Noguchi
mesh_terms: D000818:Animals; D015536:Down-Regulation; D006941:Hyperesthesia / Q000378:metabolism*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism; D013127:Spinal Nerves / Q000293:injuries* / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D014110:Touch
chemical_list: D018836:Inflammation Mediators; D051196:Toll-Like Receptor 3