Cannabinoid Modulation of Inflammed Nociceptors

描述(申请人提供)：大麻的止痛特性已经被注意了几个世纪。然而，由于大麻的精神活性和滥用倾向，使用大麻治疗疼痛是有限的。通过选择性激活外周大麻素受体，仍有可能用于治疗。大麻素1(CB1)受体定位于初级传入神经元和皮肤神经末梢。此外，先前使用急性和持续性疼痛(如炎症)的动物模型的研究表明，局部使用大麻受体激动剂可以产生外周介导的止痛作用。在这种外周介导的止痛中，大麻类物质在多大程度上改变了伤害性感受器的反应目前尚不清楚。 利用相关的行为学和活体梳理纤维电生理学方法，本提案的总体目标是确定大麻素减轻痛觉过敏的外周神经机制。我们推测，在佐剂诱发的炎症过程中，外周CB1受体的激活将降低皮肤A6和C伤害性感受器的诱发反应，并减轻痛觉过敏。 公共卫生相关性： 这些研究将为深入了解大麻素介导的镇痛的外周机制提供帮助。研究结果可能会对治疗疼痛的新型外周作用药物的未来发展产生直接影响。

DESCRIPTION (provided by applicant): The analgesic properties of cannabis have been noted for centuries. However, the use of cannabis to treat pain is limited due to its psychoactive properties and abuse liability. Therapeutic applications may still be possible through the selective activation of peripheral cannabinoid receptors. Cannabinoid 1 (CB1) receptors have been localized to primary afferent neurons and cutaneous nerve terminals. Also, previous studies using animal models of both acute and persistent pain, such as inflammation, have demonstrated that locally administered cannabinoid receptor agonists produce peripherally mediated antihyperalgesia. The extent to which cannabinoids alter responses of nociceptors in this peripherally mediated antihyperalgesia is not currently known. Using correlative behavioral and in vivo teased-fiber electrophysiological methods, the overall objective of this proposal is to determine the peripheral neural mechanisms by which cannabinoid decrease hyperalgesia. We hypothesize that during adjuvant-evoked inflammation, activation of peripheral CB1 receptors will decrease the evoked responses of cutaneous A6 and C nociceptors and attenuate hyperalgesia. PUBLIC HEALTH RELEVANCE: These studies will provide insight into the peripheral mechanisms of cannabinoid-mediated analgesia. Results may have a direct impact on the future development of novel, peripherally acting medications to treat pain.