Trigeminal neuropathic pain(TNP)is a significant health problem but the involved mechanism has not been completely elucidated.Toll-like receptors(TLRs)have recently been demonstrated to be expressed in the dorsal root...Trigeminal neuropathic pain(TNP)is a significant health problem but the involved mechanism has not been completely elucidated.Toll-like receptors(TLRs)have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain.Here,we show that TLR8 was persistently increased in the trigeminal ganglion(TG)neurons in model of TNP induced by partial infraorbital nerve ligation(pIONL).In addition,deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia,reduced the activation of ERK and p38-MAPK,and decreased the expression of pro-inflammatory cytokines in the TG.Furthermore,intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity.VTX-2337 also increased the intracellular Ca^(2+)concentration,induced the activation of ERK and p38,and increased the expression of pro-inflammatory cytokines in the TG.These data indicate that TLR8 contributes to the maintenance of TNP through increasing MAPK-mediated neuroinflammation.Targeting TLR8 signaling may be effective for the treatment of TNP.展开更多
基金the National Natural Science Foundation of China(31970938,31671091,31871064,81571070,and 31700899)the Natural Science Research Program of Jiangsu Province,China(BK20171255 and BK20191448)+1 种基金the Qing Lan Projectthe Innovation and Entrepreneurship Training Program for College Students in Jiangsu Province,China(201810304029Z)。
文摘Trigeminal neuropathic pain(TNP)is a significant health problem but the involved mechanism has not been completely elucidated.Toll-like receptors(TLRs)have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain.Here,we show that TLR8 was persistently increased in the trigeminal ganglion(TG)neurons in model of TNP induced by partial infraorbital nerve ligation(pIONL).In addition,deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia,reduced the activation of ERK and p38-MAPK,and decreased the expression of pro-inflammatory cytokines in the TG.Furthermore,intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity.VTX-2337 also increased the intracellular Ca^(2+)concentration,induced the activation of ERK and p38,and increased the expression of pro-inflammatory cytokines in the TG.These data indicate that TLR8 contributes to the maintenance of TNP through increasing MAPK-mediated neuroinflammation.Targeting TLR8 signaling may be effective for the treatment of TNP.
