The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain
The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain
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DOI：
10.1016/j.euroneuro.2013.10.008
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发表时间：
2014-04-01
影响因子：
5.6
通讯作者：
Zimmer, A.
中科院分区：
文献类型：
--
作者：
Klauke, A. -L.;Racz, I.;Zimmer, A.
广泛存在的植物挥发性β-石竹烯(BCP)是外周表达的大麻素受体2(CB2)的天然选择性激动剂。在许多香料和食用植物中，它的浓度相对较高。许多研究表明，CB2在炎症和神经病理性疼痛反应的调节中起着至关重要的作用。在本研究中，我们在炎症和神经病理性疼痛的动物模型上观察了BCP的镇痛作用。我们证明，口服BCP以CB2受体依赖的方式减少福尔马林试验中的炎性(晚期)疼痛反应，而对急性(早期)反应没有影响。在神经病理性疼痛模型中，长期口服BCP可减轻热痛觉过敏和机械性异位痛觉，并减少脊髓神经炎症。重要的是，在长期治疗后，我们没有发现对BCP的抗痛敏作用有耐受性的迹象。口服BCP比皮下注射合成CB2激动剂JWH-133更有效。因此，天然植物产品BCP在治疗持久、衰弱的疼痛状态方面可能非常有效。我们的结果对于饮食因素在慢性疼痛条件的发展和调节中的作用具有重要的意义。(C)2013年爱思唯尔和ECNP。版权所有。
The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressed cannabinoid receptor 2 (CB2). It is found in relatively high concentrations in many spices and food plants. A number of studies have shown that CB2 is critically involved in the modulation of inflammatory and neuropathic pain responses. In this study, we have investigated the analgesic effects of BCP in animal models of inflammatory and neuropathic pain. We demonstrate that orally administered BCP reduced inflammatory (late phase) pain responses in the formalin test in a CB2 receptor-dependent manner, while it had no effect on acute (early phase) responses. In a neuropathic pain model the chronic oral administration of BCP attenuated thermal hyperalgesia and mechanical allodynia, and reduced spinal neuroinflammation. Importantly, we found no signs of tolerance to the anti-hyperalgesic effects of BCP after prolonged treatment. Oral BCP was more effective than the subcutaneously injected synthetic CB2 agonist JWH-133. Thus, the natural plant product BCP may be highly effective in the treatment of long lasting, debilitating pain states. Our results have important implications for the role of dietary factors in the development and modulation of chronic pain conditions. (C) 2013 Elsevier B.V. and ECNP. All rights reserved.