Abstract
Background: Trigeminal neuropathic pain (TNP) is a significant health problem whereas the involved mechanism has not been completely elucidated. Toll-like receptors (TLRs) are recently demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain. How TLR8 is expressed in the trigeminal ganglion (TG) after infraorbital nerve injury and whether TLR8 is involved in TNP have not been investigated.Methods: TNP model was established by the partial infraorbital nerve ligation (pIONL) in mice. The effect of TLR8 and its agonist VTX-2337 on pain hypersensitivity was checked by facial pain behavioral test. The immunostaining, real-time RT-PCR, and western blot were used to evaluate the expression of TLR8, pERK, pp38, and proinflammatory cytokines in the TG. The intracellular concentration of Ca 2+ was detected by the calcium imaging.Results: TLR8 was persistently increased in TG neurons in pIONL-induced TNP model. In addition, deletion of Tlr8 or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia, reduced the activation of ERK and p38, and decreased the expression of proinflammatory cytokines in the TG. Furthermore, intra-TG injection of TLR8 agonist VTX-2337 induced facial pain hypersensitivity. VTX-2337 also increased intracellular calcium concentration, induced activation of ERK and p38, and increased the proinflammatory cytokines expression in the TG.Conclusions: TLR8 contributes to the maintenance of TNP through increasing MAPK-mediated neuroinflammation. Targeting TLR8 signaling may be effective for the treatment of TNP.
Physiological and anatomical consequences of infraorbital nerve transection in the trigeminal ganglion and trigeminal spinal tract of the adult rat
