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Morphine restores and naloxone-precipitated withdrawal depresses wheel running in rats with hindpaw inflammation
Pharmacology Biochemistry and Behavior ( IF 3.6 ) Pub Date : 2021-08-04 , DOI: 10.1016/j.pbb.2021.173251
Michael M Morgan 1 , Kristin Ataras 1
Affiliation  

Opioids such as morphine are the most effective treatment for pain, but termination of opioid use can produce severe withdrawal symptoms. The present study models this process by using home cage wheel running to assess well-being as a result of pain, morphine analgesia, and opioid withdrawal. Injection of CFA into the right hindpaw caused a dramatic decrease in wheel running and body weight. Implantation of two morphine pellets (75 mg each) resulted in an increase in body weight on Day 1 of administration and a more gradual restoration of wheel running that was only evident during the dark phase of the circadian cycle on Days 3 and 4 of morphine administration. Continuous morphine administration decreased wheel running during the relatively inactive light phase. These findings are consistent with the clinical goal of pain therapeutics to restore normal activity during the day and facilitate sleep at night. Administration of naloxone (1 mg/kg) on Day 5 of morphine administration depressed wheel running for approximately 4 h and caused an increase in wet dog shakes. Naloxone-precipitated changes were no longer evident 6 h after administration. These findings demonstrate that the use of morphine to treat pain does not protect against opioid withdrawal. Moreover, this study provides additional support for the use of home cage wheel running as a method to assess changes in well-being as a result of pain, analgesia, and opioid withdrawal.



中文翻译:

吗啡恢复和纳洛酮沉淀的戒断抑制后爪炎症大鼠的车轮运转

吗啡等阿片类药物是最有效的疼痛治疗方法,但停止使用阿片类药物会产生严重的戒断症状。本研究通过使用家庭笼轮运行来模拟这一过程,以评估疼痛、吗啡镇痛和阿片类药物戒断导致的幸福感。将 CFA 注射到右后爪中导致车轮运行和体重急剧下降。植入两个吗啡药丸(每个 75 毫克)导致在给药的第 1 天体重增加,并且车轮运行的逐渐恢复,这仅在吗啡给药的第 3 天和第 4 天的昼夜周期的黑暗阶段才明显. 在相对不活跃的光照阶段,连续的吗啡给药减少了车轮运行。这些发现与疼痛治疗的临床目标一致,即在白天恢复正常活动并促进夜间睡眠。在吗啡给药的第 5 天给药纳洛酮 (1 mg/kg) 压下车轮运行约 4 小时,并导致湿狗震动增加。给药后 6 小时纳洛酮沉淀的变化不再明显。这些发现表明,使用吗啡治疗疼痛并不能防止阿片类药物戒断。此外,这项研究为使用家庭笼轮跑步作为评估疼痛、镇痛和阿片类药物戒断引起的幸福感变化的方法提供了额外的支持。在吗啡给药的第 5 天给药纳洛酮 (1 mg/kg) 压下车轮运行约 4 小时,并导致湿狗震动增加。给药后 6 小时纳洛酮沉淀的变化不再明显。这些发现表明,使用吗啡治疗疼痛并不能防止阿片类药物戒断。此外,这项研究为使用家庭笼轮跑步作为评估疼痛、镇痛和阿片类药物戒断引起的幸福感变化的方法提供了额外的支持。在吗啡给药的第 5 天给药纳洛酮 (1 mg/kg) 压下车轮运行约 4 小时,并导致湿狗震动增加。给药后 6 小时纳洛酮沉淀的变化不再明显。这些发现表明,使用吗啡治疗疼痛并不能防止阿片类药物戒断。此外,这项研究为使用家庭笼轮跑步作为评估疼痛、镇痛和阿片类药物戒断引起的幸福感变化的方法提供了额外的支持。

更新日期:2021-08-07
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