NEUROLOGICAL BASIS OF PAIN: ROLE OF CANNABINOIDS

疼痛的神经学基础：大麻素的作用

• 批准号: 6529145
• 负责人: J. Michael Walker
• 金额: $ 20.09万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6529145
• 关键词: cannabinoids; chronic pain; disease /disorder model; laboratory rat; nerve injury; neural information processing; neuroanatomy; neuropharmacology; pain; periaqueductal gray matter; sciatic nerve; sensory mechanism; spinal cord; spinal ganglion

DESCRIPTION: (Adapted from the Investigator's Abstract) The neurobiological basis of pain and the neural circuits that underlie pain perception and pain inhibition remain fundamental problems for neuroscientists. Much research in the past 25 years has focused on mechanisms in the brain that modulate pain sensitivity, especially those mechanisms related to the neurotransmitters and neuromodulators that control acute and chronic pain. Marijuana has been used for pain relief for centuries, but only recently has the mechanism of its actions on the neural processing of painful inputs been studied. Cannabinoids depress the reaction of nociceptive neurons in the spinal cord, lateral and medial thalamus. This action takes place by effects of cannabinoids on specific brain structures, the spinal cord, and the peripheral nerve itself. Besides depressing acute or nociceptive pain, cannabinoids are active in models of chronic pain, inflamation neuropathic pain and in an electrophysiological model of windup. Virtually nothing is known about the neuronal mechanisms of cannabinoid suppression of the pathological pain produced by nerve injury, which is the subject of this renewal application. The proposed experiments examine the effects of a cannabinoid agonist on pain behavior and spinal neural processing of tactile inputs in rats with chronic constriction injury of the sciatic nerve. The proposed studies further examine the effects of a cannabinoids on abnormally high levels of spontaneous discharge, the hyper excitability of mild and noxious mechanical stimuli and responses to stimulation of different peripheral fiber types. Pharmacological specificity will be examined using selective CB1 and CB2 cannabinoid receptor antagonists. These studies may shed light on the actions of endogenous cannabinoids in chronic pain because any effects of a cannabinoid antagonist that is opposite to that of an agonist may be the result of blockade of an endogenous modulator of the cannabinoid receptor. The sites of action of the drug will be examined in studies in which the compounds are applied locally to a specific brain region (the dorsal periaquductal gray), the spinal cord, the dorsal root ganglion or at the site of injury. The results of these studies will reveal mechanisms by which cannabinoids modulate the pathological pain, and suggests future studies directed at determining the role of endocannabinoids in pain processing.

描述：(改编自《调查者摘要》) 疼痛的神经生物学基础和疼痛背后的神经回路 感知和疼痛抑制仍然是神经科学家面临的基本问题。 在过去的25年里，许多研究都集中在大脑中的机制上 调节疼痛敏感性，特别是那些与 控制急性和慢性疼痛的神经递质和神经调节剂。 几个世纪以来，大麻一直被用来缓解疼痛，但直到最近才开始使用 其在痛觉输入的神经加工中的作用机制 学习。大麻素抑制脊髓内伤害性神经元的反应 脊髓、外侧和内侧丘脑。此操作的发生受以下影响 大麻素对特定的脑结构、脊髓和外周的影响 神经本身。除了抑制急性或伤害性疼痛，大麻类药物还 在慢性疼痛、炎症性神经病理性疼痛模型和 发条的电生理模型。 对大麻素的神经机制几乎一无所知。 抑制神经损伤产生的病理性疼痛，这是 此续期申请的标的。拟议中的实验检验了 大麻素激动剂对疼痛行为和脊髓神经加工的影响 坐骨神经慢性挤压伤大鼠触觉输入的变化 很有胆量。拟议的研究进一步考察了一种大麻类物质对 异常高水平的自发放电，轻度的过度兴奋 和有害的机械刺激以及对不同刺激的反应 外围光纤类型。药理特异度将用 选择性CB1和CB2大麻素受体拮抗剂。这些研究可能会使 内源性大麻素在慢性疼痛中的作用 与激动剂相反的大麻素拮抗剂的作用可能 是大麻素的内源性调节剂被阻断的结果 受体。药物的作用部位将在以下研究中进行检查 这些化合物局部应用于特定的大脑区域(背侧 导管周围灰质)、脊髓、背根神经节或在该部位 受伤的原因。这些研究的结果将揭示 大麻素调节病理性疼痛，并建议未来的研究 旨在确定内源性大麻素在疼痛处理中的作用。