Department of Pharmacology, Daiichi College of Pharmaceutical Sciences, Fukuoka, Japan.
Eur J Pain. 2013 May;17(5):664-75. doi: 10.1002/j.1532-2149.2012.00242.x. Epub 2012 Nov 9.
β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis. The present study investigated the contribution of peripheral cannabinoid (CB) and opioid systems in the antinociception produced by intraplantar (i.pl.) injection of BCP. The interaction between peripheral BCP and morphine was also examined.
The antinociceptive effect of i.pl. BCP was assayed by the capsaicin tests in mice. Antagonists for CB and opioid receptors, and antisera against β-endorphin were injected peripherally prior to i.pl. injection of BCP. Morphine in combination with BCP was injected subcutaneously or intrathecally.
The i.pl. injection of BCP dose-dependently attenuated capsaicin-induced nociceptive response. The antinociceptive effect produced by BCP was prevented by pretreatment with AM630, a selective CB2 receptor antagonist, but not by AM251, a selective CB1 receptor antagonist. Pretreatment with naloxone, an opioid receptor antagonist, and β-funaltrexamine, a selective μ-opioid receptor antagonist, reversed the antinociceptive effect of BCP. Pretreatment with naloxone methiodide, a peripherally acting antagonist for opioid receptors and antisera against β-endorphin, resulted in a significant antagonizing effect on BCP-induced antinociception. Morphine-induced antinociception was increased by a low dose of BCP. The increased effect of morphine in combination with BCP was antagonized significantly by pretreatment with naloxone.
The present results demonstrate that antinociception produced by i.pl. BCP is mediated by activation of CB2 receptors, which stimulates the local release from keratinocytes of the endogenous opioid β-endorphin. The combined injection of morphine and BCP may be an alternative in treating chemogenic pain.
β-石竹烯(BCP)是许多香料、食用植物精油的常见成分,也是大麻的主要成分。本研究探讨了周围大麻素(CB)和阿片系统在足底注射 BCP 产生的镇痛中的作用。还研究了外周 BCP 和吗啡之间的相互作用。
通过辣椒素试验检测足底注射 BCP 的镇痛作用。在足底注射 BCP 之前,外周注射 CB 和阿片受体拮抗剂以及针对β-内啡肽的抗血清。将吗啡与 BCP 联合皮下或鞘内注射。
足底注射 BCP 呈剂量依赖性地减弱辣椒素诱导的痛觉反应。BCP 产生的镇痛作用被选择性 CB2 受体拮抗剂 AM630 预处理所预防,但不被选择性 CB1 受体拮抗剂 AM251 预防。阿片受体拮抗剂纳洛酮和选择性μ-阿片受体拮抗剂β-呋喃他胺预处理逆转了 BCP 的镇痛作用。纳洛酮甲碘化物,一种外周作用的阿片受体拮抗剂和针对β-内啡肽的抗血清,对 BCP 诱导的镇痛作用有显著的拮抗作用。吗啡诱导的镇痛作用被低剂量的 BCP 增强。纳洛酮预处理显著拮抗了吗啡与 BCP 联合使用的增强作用。
本研究结果表明,足底注射 BCP 产生的镇痛作用是通过激活 CB2 受体介导的,该受体刺激角质形成细胞内源性阿片β-内啡肽的局部释放。吗啡和 BCP 的联合注射可能是治疗化学性疼痛的一种替代方法。