Khasabova Iryna A, Gielissen James, Chandiramani Anisha, Harding-Rose Catherine, Odeh Desiree Abu, Simone Donald A, Seybold Virginia S
Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota, USA.
Behav Pharmacol. 2011 Sep;22(5-6):607-16. doi: 10.1097/FBP.0b013e3283474a6d.
In light of the adverse side-effects of opioids, cannabinoid receptor agonists may provide an effective alternative for the treatment of cancer pain. This study examined the potency and efficacy of synthetic CB1 and CB2 receptor agonists in a murine model of tumor pain. Intraplantar injection of the CB1 receptor agonist arachidonylcyclopropylamide (ED(50) of 18.4 μg) reduced tumor-related mechanical hyperalgesia by activation of peripheral CB1 but not CB2 receptors. Similar injection of the CB2 receptor agonist AM1241 (ED50 of 19.5 μg) reduced mechanical hyperalgesia by activation of peripheral CB2 but not CB1 receptors. Both agonists had an efficacy comparable with that of morphine (intraplantar), but their analgesic effects were independent of opioid receptors. Isobolographic analysis of the coinjection of arachidonylcyclopropylamide and AM1241 determined that the CB1 and CB2 receptor agonists interacted synergistically to reduce mechanical hyperalgesia in the tumor-bearing paw. These data extend our previous findings that the peripheral cannabinoid receptors are a promising target for the management of cancer pain and mixed cannabinoid receptor agonists may have a therapeutic advantage over selective agonists.
鉴于阿片类药物的不良副作用，大麻素受体激动剂可能为癌症疼痛的治疗提供一种有效的替代方案。本研究在小鼠肿瘤疼痛模型中检测了合成的CB1和CB2受体激动剂的效力和疗效。足底注射CB1受体激动剂花生四烯酰环丙酰胺（半数有效剂量为18.4μg）通过激活外周CB1而非CB2受体减轻了肿瘤相关的机械性痛觉过敏。类似地，注射CB2受体激动剂AM1241（半数有效剂量为19.5μg）通过激活外周CB2而非CB1受体减轻了机械性痛觉过敏。两种激动剂的疗效与吗啡（足底注射）相当，但它们的镇痛作用独立于阿片受体。对花生四烯酰环丙酰胺和AM1241联合注射的等效应线分析确定，CB1和CB2受体激动剂协同作用以减轻荷瘤爪的机械性痛觉过敏。这些数据扩展了我们之前的发现，即外周大麻素受体是管理癌症疼痛的一个有前景的靶点，混合大麻素受体激动剂可能比选择性激动剂具有治疗优势。
