Mechanism of mitigation of neuropathic pain by spinal cord stimulation in rats: the relationship with HMGB1/TLR4/NF-κB signaling pathway in the spinal cord
Yuan Baohong, Liu Xiaonan, Liu Danyan
Published 2014-07-20
Cite as Chin J Anesthesiol, 2014,34(07): 789-792. DOI: 10.3760/cma.j.issn.0254-1416.2014.07.003
Abstract
Objective To investigate the relationship between the mechanism of mitigation of neuropathic pain by spinal cord stimulation (SCS) and high mobility group protein box-1 (HMGB1)/Toll-like receptor 4 (TLR4)/NF-κB signaling pathway in the spinal cord of rats.Methods Forty-eight male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were randomly divided into 4 groups (n =12 each) using a random number table:sham operation group (S group),chronic constrictive injury (CCI) group,sham SCS group (S-SCS group),and SCS group.Neuropathic pain was induced by CCI in the animals anesthetized with intraperitoneal chloral hydrate.The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread.Electrodes were placed into the epidural space at 5 days after CCI in S-SCS and SCS groups,and in addition SCS was performed at 12-14 days after CCI in SCS group.Paw withdrawal threshold to mechanical stimulation (MWT) were measured at 1 day before operation and 1,4,7,14 days after CCI.After measurement of pain threshold at day 14 after CCI,the animals were sacrificed and the lumbar segments (L4-6) of the spinal cord were obtained for determination of mRNA expression of HMGB1,TLR4,and NF-κB p65 (in the nuclear protein,by real-time fluorescent quantitative PCR),protein expression of TLR4 and NF-κBp65 (by Western blot),and protein expression of HMGB1 (by immunohistochemistry).Results Compared with S group,MWT was significantly decreased after CCI,the mRNA and protein expression of HMGB1 and TLR4 was up-regulated,and the expression of NF-κB p65in the nuclear protein and mRNA was up-regulated in CCI,S-SCS and SCS groups.Compared with CCI group,MWT was significantly increased after spinal cord stimulation,the mRNA and protein expression of HMGB1 and TLR4 was down-regulated,and the expression of NF-κB p65 in the nuclear protein and mRNA was down-regulated in SCS group.Conclusion The mechanism by which SCS mitigates neuropathic pain may be related to inhibition of HMGB1/TLR4/NF-κB signaling pathway in the spinal cord of rats.
Key words:
Electric stimulation; Neuralgia; Spinal cord; High mobility group proteins; Toll-like receptor 4; NF-kappaB
Contributor Information
Yuan Baohong
Department of Anesthesiology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Liu Xiaonan
Department of Anesthesiology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Liu Danyan
Department of Anesthesiology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China