Pain Management and Research
Effect of dexmedetomidine on spinal P2X4/NLRP3 pathway in a rat model of diabetic neuropathic pain
Liu Kang, Xia Zhongyuan, Zhao Bo, Zhou Fang, Xiao Yun, Hou Jiabao
Published 2017-05-20
Cite as Chin J Anesthesiol, 2017,37(05): 536-539. DOI: 10.3760/cma.j.issn.0254-1416.2017.05.007
Abstract
ObjectiveTo 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).
MethodsTwenty-four pathogen-free adult male Sprague-Dawley rats, weighing 200-220 g, aged 8 weeks, were allocated into 3 groups (n=8 each) using a random number table: control 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-1beta (IL-1β) expression (by Western blot). The sural nerve was obtained for examination of the ultrastructure by electron microscopy.
ResultsCompared 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.
ConclusionThe mechanism by which dexmedetomidine mitigates DNP is probably related to inhibition of P2X4/NLRP3 pathway in rats.
Key words:
Dexmedetomidine; Diabetes mellitus; Neuralgia; Receptors, purinergic P2; NLRP3 inflammasome
Contributor Information
Liu Kang
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
Xia Zhongyuan
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
Zhao Bo
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
Zhou Fang
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
Xiao Yun
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
Hou Jiabao
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
