CANNABINOID MODULATION OF HYPERALGESIA

描述：（改编自研究者摘要） 持续性疼痛和皮肤痛觉过敏与许多疼痛相关， 综合征传统的疼痛管理方法，如麻醉剂， 由于其不利的副作用，如耐受性和添加， 大麻素类药物的镇痛特性已被公认多年 但直到最近， 阐明。虽然大麻素传统上被认为可以产生 它们通过在中枢神经系统中的作用而具有抗伤害感受特性， 最近的证据表明，大麻素可能产生抗伤害感受， 外围的此外，低剂量的大麻素可能非常有效， 缓解痛觉过敏。 拟议的研究将调查周围神经机制， 有助于大麻素介导的抗伤害感受。我们的初步数据 提示：1）大麻素受体位于背根神经节（DRG） 含有降钙素基因相关肽（CGRP）的神经元; 2）足底 鞘内注射大麻素可以防止 辣椒素引起的痛觉过敏; 3）大麻素减少诱发释放的 来自培养的DRG神经元的GCRP。为了进一步研究外周机制， 大麻素抗伤害性，我们建议：确定抗痛觉过敏， 使用辣椒素的足底和鞘内大麻素的性质， 角叉菜胶炎症模型（目的1）;以确定是否大麻素 减少由辣椒素产生的皮肤伤害感受器的致敏作用， 角叉菜胶（目的2）;并确定大麻素是否减少递质 在体外和体内从初级传入纤维释放，并研究 基本机制。 这些研究将提供新的信息， 大麻素产生抗伤害感受。此外，结果将直接 大麻素通过外周神经通路减轻痛觉过敏的临床意义 机制等外周大麻素可能对管理某些 慢性疼痛，没有与传统药物相关的不良副作用 治疗

DESCRIPTION: (Adapted from the Investigator's Abstract) Persistent pain and cutaneous hyperalgesia are associated with many painful syndromes. Traditional pain management approaches, such as with narcotics, are problematic due to their adverse side effects such as tolerance and addition. Analgesic properties of cannabinoid drugs have been acknowledged for many years but it is only recently that the underlying neural mechanisms are being elucidated. Although cannabinoids have been traditionally believed to produce their antinociceptive properties through actions in the central nervous system, recent evidence suggests that cannabinoids may produce antinociception peripherally. Moreover, low doses of cannabinoids may be very effective in relieving hyperalgesia. The proposed studies will investigate the peripheral neural mechanisms that contribute to cannabinoid-mediated antinociception. Our preliminary data suggest that 1) cannabinoid receptors are located on dorsal root ganglion (DRG) neurons that contain calcitonin gene-related peptide (CGRP); 2) intraplantar and intrathecal injection of cannabinoids prevent the development of hyperalgesia produced by capsaicin; 3) cannabinoids decrease evoked release of GCRP from cultured DRG neurons. To further investigate peripheral mechanisms of cannabinoid antinociception, we propose: to determine antihyperalgesic properties of intarplantar and intrathecal cannabinoids using the capsaicin and carrageenan models of inflammation (Aim 1); to determine whether cannabinoids reduce sensitization of cutaneous nociceptors produced by capsaicin and carrageenan (Aim 2); and to determine whether cannabinoids decrease transmitter release from primary afferent fibers in vitro and in vivo, and investigate underlying mechanisms. These studies will provide new information on the mechanisms by which cannabinoids produce antinociception. Moreover, results will have direct clinical significance if cannabinoids attenuate hyperalgesia through peripheral mechanisms. Peripheral cannabinoids may be very effective for managing certain chronic pains without undesirable side effects associated with traditional therapies.