Background Opioid switching is a therapeutic maneuver to improve analgesic response and/or reduce adverse side effects although the underlying mechanisms remain unknown.The μ-opioid receptor （MOR） has an important ...Background Opioid switching is a therapeutic maneuver to improve analgesic response and/or reduce adverse side effects although the underlying mechanisms remain unknown.The μ-opioid receptor （MOR） has an important role in mediating the actions of morphine and other analgesic agents.This study is aimed at exploring the changes of MOR in the periaqueductal gray （PAG） in rats when morphine is substituted for equianalgesic fentanyl.Methods Forty rats were randomly assigned to five treatment groups：7 days normal saline group （N group）,7 days fentanyl group （F group）,7 days morphine group （M group）,7 days morphine and 7 days fentanyl-switching group （MF group）,and 14 days morphine group （MM group）.Rats repeatedly received subcutaneous injections of morphine sulfate （10 mg/kg） or equianalgesic fentanyl sulfate （0.1 mg/kg） twice daily.Rats＇ antinociceptive response to thermal pain was evaluated by the tail flick latency assay.MOR mRNA and protein expression in the PAG were measured using RT-PCR and Western blotting analyses respectively.Results This study showed that after morphine was substituted with fentanyl on day 8,the tail flick latency （TFL） increased from （3.9±0.4） seconds to （11.4±0.4） seconds.The results also demonstrated that both MOR mRNA and protein expression in the PAG of rats in the MF group were less than that in the M group （P〈0.05） but more than that in MM group （P〈0.05）.Conclusions Equianalgesic fentanyl was still antinociceptive effective in rats with morphine tolerance,which may be due to the switching from morphine to fentanyl attenuating the decline of MOR expression in the PAG of rats.展开更多
目的观察中枢与外周β-内啡肽对缺血后心肌的影响及其在侧脑室吗啡预处理减轻大鼠心肌缺血/再灌注损伤中的含量变化,探讨β-内啡肽在中枢吗啡预处理在体大鼠缺血后心肌保护作用中的角色。方法66只♂SD大鼠,分别建立侧脑室微量注射和心...目的观察中枢与外周β-内啡肽对缺血后心肌的影响及其在侧脑室吗啡预处理减轻大鼠心肌缺血/再灌注损伤中的含量变化,探讨β-内啡肽在中枢吗啡预处理在体大鼠缺血后心肌保护作用中的角色。方法66只♂SD大鼠,分别建立侧脑室微量注射和心肌缺血/再灌注损伤动物模型。随机分为假手术(Sham)组、缺血对照(CON)组、缺血预处理(IPC)组、中枢和外周β-内啡肽激动剂(Icv/Iv-EP)组、中枢吗啡预处理(MPC组)、中枢β-内啡肽阻断剂(Icv-MPC-Anti-EP/Icv-Anti-EP-MPC)组、外周β-内啡肽阻断剂(Icv-MPC+Iv-Anti-EP)组、中枢和外周β-内啡肽阻断剂自身对照(Icv/Iv-Anti-EP)组。观察平均动脉压(MAP)、心率(HR)、压力心率乘积(RPP)、缺血危险区(AAR)、梗死区(IS)体积、IS/AAR等的变化;同时以免疫组化观察下丘脑弓状核(arcuate nucleus,ARC),中脑导水管周围灰质(periaque-ductalgray,PAG)及左室心肌(myocardium of left ventricle,MC)β-内啡肽的阳性表达。结果与CON组相比,IPC、MPC、Icv-EP、Iv-EP、Icv-Anti-EP-MPC、Icv-MPC+Iv-Anti-EP组均明显降低IS/AAR(P<0.01);Icv-MPC-Anti-EP组虽然取消MPC的保护效应(P<0.01),但较CON组差异仍有统计学意义(P<0.05);与CON组相比,MPC组减弱了ARC中β-内啡肽的阳性表达(P<0.05),同时明显增强PAG和左室心肌的免疫反应强度(P<0.05;P<0.01)。结论中枢与外周β-内啡肽对缺血后心肌损伤有保护作用;侧脑室吗啡预处理后可能促进下丘脑弓状核释放β-内啡肽,后者作为神经递质部分参与了中枢吗啡预处理介导的心肌保护效应。展开更多
文摘Background Opioid switching is a therapeutic maneuver to improve analgesic response and/or reduce adverse side effects although the underlying mechanisms remain unknown.The μ-opioid receptor （MOR） has an important role in mediating the actions of morphine and other analgesic agents.This study is aimed at exploring the changes of MOR in the periaqueductal gray （PAG） in rats when morphine is substituted for equianalgesic fentanyl.Methods Forty rats were randomly assigned to five treatment groups：7 days normal saline group （N group）,7 days fentanyl group （F group）,7 days morphine group （M group）,7 days morphine and 7 days fentanyl-switching group （MF group）,and 14 days morphine group （MM group）.Rats repeatedly received subcutaneous injections of morphine sulfate （10 mg/kg） or equianalgesic fentanyl sulfate （0.1 mg/kg） twice daily.Rats＇ antinociceptive response to thermal pain was evaluated by the tail flick latency assay.MOR mRNA and protein expression in the PAG were measured using RT-PCR and Western blotting analyses respectively.Results This study showed that after morphine was substituted with fentanyl on day 8,the tail flick latency （TFL） increased from （3.9±0.4） seconds to （11.4±0.4） seconds.The results also demonstrated that both MOR mRNA and protein expression in the PAG of rats in the MF group were less than that in the M group （P〈0.05） but more than that in MM group （P〈0.05）.Conclusions Equianalgesic fentanyl was still antinociceptive effective in rats with morphine tolerance,which may be due to the switching from morphine to fentanyl attenuating the decline of MOR expression in the PAG of rats.
文摘目的观察中枢与外周β-内啡肽对缺血后心肌的影响及其在侧脑室吗啡预处理减轻大鼠心肌缺血/再灌注损伤中的含量变化,探讨β-内啡肽在中枢吗啡预处理在体大鼠缺血后心肌保护作用中的角色。方法66只♂SD大鼠,分别建立侧脑室微量注射和心肌缺血/再灌注损伤动物模型。随机分为假手术(Sham)组、缺血对照(CON)组、缺血预处理(IPC)组、中枢和外周β-内啡肽激动剂(Icv/Iv-EP)组、中枢吗啡预处理(MPC组)、中枢β-内啡肽阻断剂(Icv-MPC-Anti-EP/Icv-Anti-EP-MPC)组、外周β-内啡肽阻断剂(Icv-MPC+Iv-Anti-EP)组、中枢和外周β-内啡肽阻断剂自身对照(Icv/Iv-Anti-EP)组。观察平均动脉压(MAP)、心率(HR)、压力心率乘积(RPP)、缺血危险区(AAR)、梗死区(IS)体积、IS/AAR等的变化;同时以免疫组化观察下丘脑弓状核(arcuate nucleus,ARC),中脑导水管周围灰质(periaque-ductalgray,PAG)及左室心肌(myocardium of left ventricle,MC)β-内啡肽的阳性表达。结果与CON组相比,IPC、MPC、Icv-EP、Iv-EP、Icv-Anti-EP-MPC、Icv-MPC+Iv-Anti-EP组均明显降低IS/AAR(P<0.01);Icv-MPC-Anti-EP组虽然取消MPC的保护效应(P<0.01),但较CON组差异仍有统计学意义(P<0.05);与CON组相比,MPC组减弱了ARC中β-内啡肽的阳性表达(P<0.05),同时明显增强PAG和左室心肌的免疫反应强度(P<0.05;P<0.01)。结论中枢与外周β-内啡肽对缺血后心肌损伤有保护作用;侧脑室吗啡预处理后可能促进下丘脑弓状核释放β-内啡肽,后者作为神经递质部分参与了中枢吗啡预处理介导的心肌保护效应。
