Purinergic receptor 3 is involved in the maintenance of trigeminal neuralgia through the p38 mitogen-activated protein kinase signaling pathway in rats
Objective To investigate the effects of purinergic receptor 3(P2X3R)on the inflamma-tory response in trigeminal neuralgia rats through the p38 mitogen-activated protein kinase(p38 MAPK)/nuclear factor-κB(NF-κB)signaling pathway and its mechanism.Methods SD rats were divided into 4 groups using a randomized numeric table method:sham operation group(S group),trigeminal neuralgia group(TN group),trigeminal neuralgia+saline group(TN+NS group),and trigeminal neuralgia+P2X3R-specific antagonist A-317491 group(TN+A-317491 group).A trigeminal neuralgia model was prepared using chronic constriction injury of the infraorbital nerve.Rats in the TN+A-317491 group were injected intraperitoneally with A-317491(0.5 mg/kg)at 3,7,10,and 14 d after modeling;rats in the TN+NS group were injected intraperitoneally with an equal dose of saline.Facial mechanical pain withdraw thresh-old(MWT)was measured at 1st d before modeling,and at 3rd,7th,10th,14th,and 28th d after model-ing(T0-5).After 28 d of modeling,the trigeminal nerve tissues were taken from the executed rats,and the expression levels of P2X3R,p38MAPK,p-p38MAPK,p-NF-κB p65 were detected by Western blotting method.The contents of tumor necrosis factor-α(TNF-α),interleukin(IL)-1 β,and IL-6 were detected by enzyme linked immunosorbent assay(ELISA).The pathological changes of trigeminal nerve tissues were observed by hematoxylin and eosin(HE)staining.The differences between groups were compared using t-tests and one-way ANOVA.Results MWT was lower in the TN group at T1-5 than in the S group,and that in the TN group at T2-5 than in the TN+A-317491 group.The expression of P2X3R,p-p38 MAPK and p-NF-κB p65 were up-regulated in the TN group compared to the S group and TN+A-317491 group(0.68±0.05 vs.0.42±0.03,0.44±0.05,F=62.838,P＜0.05;0.84±0.01 vs.0.48±0.05,0.49±0.06,F=165.036,P＜0.05;0.88±0.03 vs.0.53±0.05,0.56±0.09,F=56.481,P＜0.05).There was an increase of TNF-α,IL-1β and IL-6 contents[(33.78±1.89)vs.(15.20±1.33),(22.02±2.30)pg/ml,F=44.956,P＜0.05;(41.92±3.03)vs.(21.82±1.95),(30.71±3.58)pg/ml,F=81.745,P＜0.05;(32.62±1.52)vs.(17.63±1.27),(23.50±1.83)pg/ml,F=65.971,P＜0.05]in the TN group compared to the S group and the TN+A-317491 group.The histopathological damage of the tri-geminal nerve was aggravated in the TN and TN+NS groups as compared with the S group,and the patholog-ical damage was reduced in the TN+A-317491 group as compared with the TN and TN+NS groups.Conclusion P2X3R is involved in the maintenance of trigeminal neuralgia in rats and may be associated with an increased inflammatory response after activation of the p38MAPK/NF-κB signaling pathway.
Trigeminal neuralgiaReceptors,purinergic P2P38 Mitogen-activated protein kinasesInflammatory responseNuclear factor-κB
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