Cannabinoid Modulation of Inflammed Nociceptors

描述（由申请人提供）：几个世纪以来，大麻的镇痛特性一直受到关注。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，治疗应用仍然是可能的。大麻素1（CB 1）受体已定位于初级传入神经元和皮肤神经末梢。此外，以前的研究使用急性和持续性疼痛，如炎症的动物模型，已经证明，局部施用大麻素受体激动剂产生外周介导的抗痛觉过敏。大麻素在这种外周介导的抗痛觉过敏中改变伤害感受器反应的程度目前尚不清楚。 使用相关的行为和在体内的挑逗纤维电生理方法，本建议的总体目标是确定大麻素减少痛觉过敏的外周神经机制。我们推测，在促炎剂诱发的炎症，外周CB1受体的激活将减少皮肤A6和C伤害性感受器的诱发反应，并减弱痛觉过敏。 公共卫生相关性： 这些研究将提供深入了解大麻素介导的镇痛外周机制。结果可能对未来开发新型外周作用药物治疗疼痛产生直接影响。

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.