TLR8 in the Trigeminal Ganglion Contributes to the Maintenance of Trigeminal Neuropathic Pain in Mice

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.

Acupuncture Treatment for Idiopathic Trigeminal Neuralgia:A Longitudinal Case-Control Double Blinded Study

Objective： To evaluate the treatment effect of acupuncture on patients with idiopathic trigeminal neuralgia（ITN） by case-control longitudinal blinded study. Methods： Sixty ITN patients and 30 healthy subjects were included. The ITN patients were randomly assigned to acupuncture group（15 cases）, sham-acupuncture group（15 cases） and carbamazepine group（30 cases）, respectively. Clinical orofacial evaluation（including pain intensity and medication doses）, research diagnostic criteria for temporomandibular disorders（RDC/TMD） and Helkimo indexes（for functional evaluation of the masticatory system）, and quantitative sensory testing for sensory thresholds（gustative, olfactory, cold, warm, touch, vibration and superficial and deep pain） were evaluated before treatment, immediately after treatment, and 6 months after treatment. Results： The mean pain intensity by the Visual Analogue Scale only decreased in the acupuncture group at the last evaluation（P=0.012）. Patients in the sham-acupuncture group had an increase in carbamazepine doses according to the prescriptions（P〈0.01）. There was a reduction in secondary myofascial pain and mandibular limitations at the acupuncture and sham-acupuncture groups, however only the acupuncture group kept the changes after 6 months（P〈0.01, P=0.023）. There was a decrease in mechanical thresholds in the acupuncture group（tactile, P〈0.01; vibration, P=0.027） and an increase in deep pain thresholds in both acupuncture and sham-acupuncture groups（P=0.013）. Conclusion： Acupuncture can be an option in the treatment of ITN due to its analgesic effect in both ITN and secondary myofascial pain associated with it.