Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation
Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation
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DOI：
10.1177/0023677214562849
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发表时间：
2015-07-01
影响因子：
2.4
通讯作者：
Arras, M.
中科院分区：
文献类型：
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作者：
Jirkof, P.;Tourvieille, A.;Arras, M.
镇痛药物的缓释制剂是重复药物注射的有希望的替代品。在这里，我们将丁丙诺啡缓释制剂（SB，2.2mg/kg）与在小鼠中注射三次丁丙诺啡（Temgesic，0.1mg/kg/8h）的标准方案进行了比较。在健康小鼠中测定丁丙诺啡血清浓度和镇痛作用（热敏感性）。此外，在剖腹手术后使用疼痛和恢复的生理学和行为学测量来评估两种方案的疼痛缓解特性。血清浓度和热敏感性测试表明，Temgesic 方案的作用持续时间至少为 4 小时（但少于 8 小时），而 SB 的作用持续时间为 24-48 小时。行为和临床参数表明两种方案手术后至少部分缓解疼痛。观察到的与方案无关的丁丙诺啡副作用是活动增加、昼夜节律紊乱和一些异常行为。还发现食物和水摄入量减少以及体重减轻的趋势。无论是否进行手术，接受 3 次 Temgesic 注射的动物体重均显着下降（P=0.015；P=0.023），暗示对这种重复干预的应激反应。总之，8 小时（Temgesic）的应用间隔似乎太长，可能会导致手术后经历持续和/或严重疼痛的动物反复出现镇痛不足的情况。与标准方案相比，SB 提供了持久、有保证的镇痛，而无需在标准手术模型中进行可能的压力性重复注射，并且仅产生有限且可接受的行为副作用。
Sustained-release formulations of analgesic drugs are promising alternatives to repeated drug injections. Here, we compared a sustained-release formulation of buprenorphine (SB, 2.2mg/kg) with a standard protocol of three injections of buprenorphine (Temgesic, 0.1mg/kg/8h) in mice. Buprenorphine serum concentration and analgesic action (thermal sensitivity) were determined in healthy mice. Additionally, the pain relief properties of both protocols were assessed after laparotomy using physiological and ethological measures of pain and recovery. Serum concentrations and thermal sensitivity tests indicated duration of action of at least 4h (but less than 8h) with the Temgesic protocol, and 24-48h with SB. Behavioural and clinical parameters indicated at least partial pain relief after surgery for both protocols. Observed side-effects of buprenorphine independent of the protocol were increased activity, disturbed circadian rhythm and several abnormal behaviours. A tendency for decreased food and water intake as well as body weight reduction was also seen. Body weight decreased significantly in animals that received three injections of Temgesic, regardless of whether surgery was performed or not (P=0.015; P=0.023), hinting at a stress response towards this repeated intervention. In conclusion, an application interval of 8h (Temgesic) appears too long and might lead to repeated periods with insufficient analgesia in animals undergoing lasting and/or substantial pain after surgery. In comparison to the standard protocol, SB provided a long-lasting, assured analgesia without possible stressful repeated injections in a standard surgical model, with only limited and acceptable behavioural side-effects.