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《Chongqing Medicine》 2017-34
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Effects of intrathecal administration of dexmedetomidine on morphine tolerance and inflammatory response in rats

Gong Hongyan;Zheng Fang;Zuo Zhichao;Liu Jingjing;Wang Qingzhi;Zhao Guoan;Department of Anesthesiology,First Affiliated Hospital of Xinxiang Medical University;Medical Imaging Center,First Affiliated Hospital of Xinxiang Medical University;School of Basic Medical Sciences,Xinxiang Medical University;  
Objective To investigate the effects of intrathecal dexmedetomidine administration on the development of morphine tolerance and spinal inflammatory responses.Methods Thirty-three male SD rats weighing 180~200 g were randomly divided into 3 groups(n=11):Saline group(group NS),Morphine group(group M)and Dexmedetomidine group(group Dex).Animals of group NS were intrathecally injected with 10μL of saline daily for seven days;Animals in group M were intrathecally injected with 15μg of morphine daily for seven days;Animals in group Dex were intrathecally injected with a mixture of 15μg morphine and1.5μg dexmedetomidine daily for seven days.At 1,3,5 and 7 day of intrathecal injection,hot water tail-flick test were used to evaluate analgesic response to thermal stimuli.After the last episode of behavioral test,Western blot analysis was applied to determine the protein levels of Iba-1(microglial marker),IL-1β,TNF-αand phospho-p38 MAPK(p-p38)in the spinal cord.In addition,microglia in the spinal cord was immuno-stained with anti-Iba-1 antibody and the densities of microglia were calculated.Results In group M and Dex,the values of maximal possible effect(MPE)in tail-flick test decreased gradually along with repeated morphine administration(P0.05).Compared with group NS,the values of MPE in tail-flick test at 1,3,5 and 7 day of morphine tolerance were higher in group M(P0.05).Compared with group M,the values of MPE in tail-flick test at 3,5 and 7 day of morphine tolerance were higher in group Dex(P0.05).Compared with group NS,the spinal protein levels of Iba-1,IL-1β,TNF-αand p-p38 as well as the density of Iba-1 positive cells in group M were increased(P0.05).However,Compared with group M,the of Iba-1,IL-1β,TNF-αand p-p38 as well as the density of Iba-1 positive cells were decreased(P0.05).Conclusion Intrathecal dexmedetomidine administration can attenuate morphine tolerance by inhibiting microglia-mediated inflammatory responses in the spinal cord.
【Fund】: 河南省医学科技攻关计划项目(201204026)
【CateGory Index】: R614
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