title: Ulinastatin attenuates neuropathic pain induced by L5-VRT via the calcineurin/IL-10 pathway.
abstract: Previous studies have shown that ulinastatin, an effective inhibitor of the inflammatory response in clinical applications, can attenuate hyperalgesia in rodents. However, the underlying mechanism remains unclear. In the present study, we first examined the change in the calcineurin level, which plays an important role in regulating cytokine release in the nervous system, following lumbar 5 ventral root transection in the rat. Furthermore, we determined whether intraperitoneal (i.p.) injection of ulinastatin attenuated pain behavior via inhibition of the calcineurin-mediated inflammatory response induced by lumbar 5 ventral root transection. The results showed that the paw withdrawal threshold and paw withdrawal latency were significantly decreased following lumbar 5 ventral root transection compared to the sham group. Neuropathic pain induced by lumbar 5 ventral root transection significantly decreased the expression of calcineurin in the DRG, and calcineurin was mostly located with NF-200-positive cells, IB4-positive cells, and CGRP-positive cells and less with GFAP-positive satellite cells. Furthermore, intrathecal (i.t.) injection of exogenous calcineurin attenuated the pain behavior induced by lumbar 5 ventral root transection. Importantly, intraperitoneal injection of ulinastatin alleviated the pain behavior and calcineurin downregulation induced by lumbar 5 ventral root transection. Lastly, the cytokine IL-10 was significantly decreased following lumbar 5 ventral root transection, and application of calcineurin (intrathecal) or ulinastatin (intraperitoneal) inhibited the IL-10 downregulation induced by lumbar 5 ventral root transection. These results suggested that ulinastatin, by acting on the CN/IL-10 pathway, might be a novel and effective drug for the treatment of neuropathic pain.
authors.affiliation: Department of Anesthesiology, Cancer Center, Sun Yat-Sen University, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Handong
authors.initials: H
authors.lastname: Ouyang
authors.affiliation: Department of Anesthesiology, Cancer Center, Sun Yat-Sen University, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Bilin
authors.initials: B
authors.lastname: Nie
authors.affiliation: Department of Anesthesiology, Cancer Center, Sun Yat-Sen University, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Peizong
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Cancer Center, Sun Yat-Sen University, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Cancer Center, Sun Yat-Sen University, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Wan
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xin
authors.affiliation: Department of Anesthesiology, Cancer Center, Sun Yat-Sen University, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China Zengwa@mail.sysu.edu.cn liuxg@mail.sysu.edu.cn.
authors.forename: Weian
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Xianguo
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D016753:Interleukin-10 / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000293:injuries*; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000293:injuries*
chemical_list: D006023:Glycoproteins; D016753:Interleukin-10; D019703:Calcineurin; C028665:urinastatin
keywords: Calcineurin; DRG; IL-10; cytokine; neuropathic pain; ulinastatin