Effect of dexmedetomidine on spinal P2X4/NLRP3 pathway in a rat model of diabetic neuropathic pain / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of dexmedetomidine on spinal purinergic receptor 2X-4 (P2X4)/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) pathway in a rat model of diabetic neuropathic pain (DNP).Methods Twenty-four pathogenfree adult male Sprague-Dawley rats,weighing 200-220 g,aged 8 weeks,were allocated into 3 groups (n =8 each) using a random number tablecontrol group (C group),DNP group and DNP plus dexmedetomidine group (DNP+D group).Diabetes mellitus was induced by intraperitoneal 1％ streptozotocin 60 mg/kg and confirmed by blood glucose ≥ 16.7 mmol/L 3 days later.In group DNP+D,dexmedetomidine 50 μg/kg was intraperitoneally injected once a day for 6 consecutive weeks starting from 3 days after the model was successfully established.The mechanical paw withdrawal threshold (MWT) and sciatic nerve conduction velocity (SNCV) were measured at 2,4 and 6 weeks after injection of dexmedetomidine.The rats were sacrificed at 6 weeks after injection of dexmedetomidine,and the L4-6 segments of the spinal cord were removed for examination of the pathological changes (with a light microscope) and for determination of P2X4,NLRP3 and interleukin-lbeta (IL-1β3) expression (by Western blot).The sural nerve was obtained for examination of the ultrastructure by electron microscopy.Results Compared with group C,the MWT was significantly decreased at 2,4 and 6 weeks after injection of dexmedetomidine,the SNCV was decreased at 6 weeks after injection of dexmedetomidine,the expression of P2X4,NLRP3 and IL-1β in the spinal cord was up-regulated (P＜0.05),and the pathological changes of the spinal cord and sural nerve were marked in DNP and DNP+D groups.Compared with group DNP,the MWT was significantly increased at 2,4 and 6 weeks after injection of dexmedetomidine,the SNCV was increased at 6 weeks after injection of dexmedetomidine,the expression of P2X4,NLRP3 and IL-1β in the spinal cord was down-regulated (P＜0.05),and the pathological changes of the spinal cord and sural nerve were significantly attenuated in group DNP+D.Conclusion The mechanism by which dexmedetomidine mitigates DNP is probably related to inhibition of P2X4/NLRP3 pathway in rats.