Effects of intrathecal administration of dexmedetomidine on morphine tolerance and inflammatory response in rats
10.3969/j.issn.1671-8348.2017.34.005
- VernacularTitle:鞘内注射右美托咪定对大鼠吗啡耐受及脊髓炎性反应的影响
- Author:
Hongyan GONG
1
;
Fang ZHENG
;
Zhichao ZUO
;
Jingjing LIU
;
Qingzhi WANG
;
Guoan ZHAO
Author Information
1. 新乡医学院第一附属医院麻醉科
- Keywords:
dexmedetomidine;
morphine;
drug tolerance;
drug tolerance;
inflammatory
- From:
Chongqing Medicine
2017;46(34):4771-4773
- CountryChina
- Language:Chinese
-
Abstract:
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 10 tμL of saline daily for seven days;Animals in group M were intrathecally injected with 15 μg of morphine daily for seven days;Animals in group Dex were intrathecally injected with a mixture of 15μg morphine and 1.5 μg 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-a and phospho-p38MAPK (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 (P＜0.05).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 (P＜0.05).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 (P＜0.05).Compared with group NS,the spinal protein levels of Iba-1,IL-1L TNF-α and p-p38 as well as the density of Iba-1 positive cells in group M were increased (P＜0.05).However,Compared with group M,the of Iba-1,IL-1β,TNF-α and p-p38 as well as the density of Iba-1 positive cells were decreased(P＜0.05).Conclusion Intrathecal dexmedetomidine administration can attenuate morphine tolerance by inhibiting microglia-mediated inflammatory responses in the spinal cord.
