右美托咪定通过抑制脊髓星形胶质细胞活化改善甲醛诱导的急性炎性痛

曾学晴; 杨彬; 周鑫; 袁婧; 谢志艳; 李威; 万炜; 刘志文; 曹文宇

doi:10.16098/j.issn.0529-1356.2021.05.002

PDF(2855 KB)

解剖学报 ›› 2021, Vol. 52 ›› Issue (5) : 681-685. DOI: 10.16098/j.issn.0529-1356.2021.05.002

神经生物学

右美托咪定通过抑制脊髓星形胶质细胞活化改善甲醛诱导的急性炎性痛

曾学晴¹ 杨彬² 周鑫³ 袁婧³ 谢志艳³ 李威³ 万炜³ 刘志文^2* 曹文宇^3*

作者信息 +

Dexmedetomidine alleviates formaldehyde induced pain by inhibiting astrocytes activation in spinal cord

ZENG Xue-qing¹ YANG Bin² ZHOU Xin³ YUAN Jing³ XIE Zhi-yan³ LI Wei³ WAN Wei³ LIU Zhi-wen^2* CAO Wen-yu^3*

Author information +

文章历史 +

摘要

目的探讨右美托咪定（DEX）在0.1%甲醛诱导的急性炎性痛中的作用。方法将30只ICR雌性小鼠随机分成生理盐水对照（NS）组、甲醛（F）组、右美托咪定+甲醛（DEX+F）组。向右后爪足底注射25 μl 0.4%甲醛建立小鼠急性炎性痛模型，在甲醛注射前1 h，DEX+F组小鼠腹腔注射DEX，NS组和F组小鼠腹腔注射等体积生理盐水。以小鼠舔咬足累计时间评价自发痛行为。采用免疫组织化学法和Western blotting检测脊髓星形胶质细胞标记物胶质纤维酸性蛋白（GFAP）的表达。结果自发痛评分结果显示，与NS组相比， F组小鼠出现典型的双相痛反应；与F组相比，DEX+F组小鼠的第Ⅰ时相痛（P<0.001）和第Ⅱ时相痛（P<0.001）累计时间明显减少。免疫组织化学结果显示，与NS组相比，F组小鼠脊髓后角GFAP阳性细胞数目明显增多（P<0.001）；与F组相比，DEX+F组小鼠脊髓后角GFAP阳性细胞数目明显减少（P<0.001）。Western blotting结果显示，与NS组相比， F组小鼠脊髓GFAP表达明显增加（P<0.05）；与F组相比，DEX+F组小鼠脊髓GFAP表达明显减少（P<0.05）。结论 DEX可能是通过抑制小鼠脊髓星形胶质细胞的活化从而改善甲醛诱导的急性炎性痛。

Abstract

Objective To investigate the effect of dexmedetomidine（DEX）on formaldehyde-induced acute inflammatory pain. Methods Thirty female ICR mice were randomly divided into three groups, including normal saline control (NS) group, formaldehyde（F）group and dexmedetomidine + formaldehyde (DEX+F) group. 0.1% formaldehyde solution was injected into subcutaneous tissue of mice right hind paw to establish acute inflammatory pain model. An hour before formalin injection, mice were intraperitoneal injected with DEX in DEX+F group, and mice were intraperitoneal injected with equal volume saline in NS group and F group. The expression of spinal cord glial fibrillary acidic protein (GFAP）, which is a astrocytes marker, was detected by immunohistochemistry and Western blotting. Results Spontaneous pain score showed that compared with the NS group, the F group had typical biphasic pain response; while compared with the F group, the DEX+F group showed a significant decrease in the first (P<0.001) and second phase pain (P<0.001). Immunohistochemical result showed that compared with the NS group, the F group had an increase number of GFAP positive cells in the posterior horn of the spinal cord (P<0.001). However, the DEX+F group showed a decrease number of GFAP positive cells in the posterior horn of spinal cord compared with the F group (P<0.001). Western blotting result showed that compared with the NS group, the F group had increased expression of GFAP in the spinal cord (P<0.05). Compared with the F group, the DEX+F group showed decreased GFAP expression in the spinal cord (P<0.05). Conclusion DEX may improve formaldehyde-induced acute inflammatory pain in mice by inhibiting the activation of astrocytes in the spinal cord.

导出引用

曾学晴杨彬周鑫袁婧谢志艳李威万炜刘志文曹文宇. 右美托咪定通过抑制脊髓星形胶质细胞活化改善甲醛诱导的急性炎性痛[J]. 解剖学报. 2021, 52(5): 681-685 https://doi.org/10.16098/j.issn.0529-1356.2021.05.002

ZENG Xue-qing YANG Bin ZHOU Xin YUAN Jing XIE Zhi-yan LI Wei WAN Wei LIU Zhi-wen CAO Wen-yu. Dexmedetomidine alleviates formaldehyde induced pain by inhibiting astrocytes activation in spinal cord[J]. Acta Anatomica Sinica. 2021, 52(5): 681-685 https://doi.org/10.16098/j.issn.0529-1356.2021.05.002

中图分类号： R322.81

参考文献

［1］ Kozlowska K, Walker P, Mclean L, et al. Fear and the defense cascade: clinical implications and management ［J］. Harv Rev Psychiatry, 2015,23(4): 263-287.
［2］ Finnerup NB, Haroutounian S, Kamerman P, et al. Neuropathic pain: an updated grading system for research and clinical practice ［J］. Pain, 2016,157(8): 1599-1606.
［3］ Orr PM, Shank BC，Black AC. The role of pain classification systems in pain management［J］.Crit Care Nurs Clin North Am,2017,29(4):407-418.
［4］ Linley JE, Rose K, Ooi L. Understanding inflammatory pain: ion channels contributing to acute and chronic nociception ［J］.Pflügers Archiv, 2010,459(5):657-669.
［5］ Karoly P.Psychosocial aspects of painrelated life task interference: an exploratory analysis in a general population sample ［J］.Pain Med, 2007,8(7):563-572.
［6］ Schmeltzer PA, Kosinski AS, Kleiner DE, et al. Liver injury from nonsteroidal anti-inflammatory drugs in the United States［J］. Liver Int，2016,36（4):603-609
［7］ Alipour M,Tabari M,Faz RF,et al.Effect of dexmedetomidine on postoperative pain in knee arthroscopic surgery; a randomized controlled clinical trial［J］. Arch Bone Jt Surg, 2014, 2(1):52-56.
［8］ Dong CS, Zhang J, Lu Q, et al. Effect of dexmedetomidine combined with sufentanil for post-thoracotomy intravenous analgesia:a randomized, controlled clinical study［J］.BMC Anesthesiol,2017,17(1):33.
［9］ Dawson C, Ma D, Chow A. Dexmedetomidine enhances analgesic action of nitrous oxide: mechanisms of action ［J］.Anesthesiology, 2004,100(4):894-904.
［10］ Sommer C, Kress M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia［J］. Neurosci Lett, 2004,361(1-3): 184-187.
［11］ Hunskaar S, Fasmer OB, Hole K. Formalin test in mice, a useful technique for evaluating mild analgesics［J］. J Neurosci Methods, 1985,14(1): 69-76.
［12］ Cao WY, Xu Y, Luo YW, et al. Activation of ERK1/2 is required for normal response of isosexual social interactions in male rats［J］. Brain Res, 2013,1538: 51-60.
［13］ Cao W, Duan J, Wang X, et al. Early enriched environment induces an increased conversion of proBDNF to BDNF in the adult rat’s hippocampus［J］. Behav Brain Res, 2014,265: 76-83.
［14］ van Boekel RL, Steegers MAH, Noord Ⅳ, et al. Acute pain services and postsurgical pain management in the Netherlands: a survey ［J］. Pain Pract, 2015,15(5): 447-454.
［15］ Bacchi S, Palumbo P, Sponta A, et al. Clinical pharmacology of non-steroidal anti-inflammatory drugs: a review［J］. Antiinflamm Antiallergy Agents Med Chem, 2012,11(1): 52-64.
［16］ Murray CW, Porreca F, Cowan A. Methodological refinements to the mouse paw formalin test. An animal model of tonic pain［J］. J Pharmacol Methods, 1988,20(2): 175-186.
［17］ Chen X, Yang Y, Liu H, et al. Effects of preemptively injected intrathecal lornoxicam on behavior and c-fos protein expression of rat with formalin hurting ［J］. Journal of Sichuan University (Medical Science Edition), 2008,39(1): 89-93.
［18］ Liu Y, Latremoliere A, Li X, et al. Touch and tactile neuropathic pain sensitivity are set by corticospinal projections ［J］. Nature, 2018,561(7724): 547-550.
［19］ Zeng JY, Wang Zh, Niu L, et al. Effect of Panax notoginseng total saponin on lipopolysaccharide induced depression-like behavior and expression of microglia in mice［J］ Acta Anatomica Sinica, 2018,49(2): 166-171. (in Chinese)
曾佳玉, 王贞, 牛磊, 等.三七总皂苷对脂多糖诱导小鼠抑郁样行为及脑内小胶质细胞表达的影响）［J］. 解剖学报, 2018,49(2): 166-171.
［20］ Lopez-Gonzalez MJ, Landry M, Favereaux A. MicroRNA and chronic pain: from mechanisms to therapeutic potential ［J］. Pharmacol Ther, 2017,180: 1-15.
［21］ Yang QQ, Zhou JW. Neuroinflammation in the central nervous system: symphony of glial cells ［J］. Glia, 2019,67(6): 1017-1035.
［22］ Leszek J, Barreto GE, Gasiorowski K, et al. Inflammatory mechanisms and oxidative stress as key factors responsible for progression of neurodegeneration: role of brain innate immune system ［J］. CNS Neurol Disord Drug Targets, 2016,15(3): 329-336.
［23］ McMahon SB, Cafferty WB. Immune and glial cell factors as pain mediators and modulators ［J］.Exp Neurol, 2005, 192(2):444-462.
［24］ Porro CA. Spatial and temporal aspects of spinal cord and brainstem activation in the formalin pain model ［J］.Prog Neurobiol, 1993, 41(5):565-607.