SPINAL NOCICEPTIVE CODING--SPATIAL-TEMPORAL MECHANISMS

脊髓伤害编码——时空机制

• 批准号: 2265051
• 负责人: DAVID J MAYER
• 金额: $ 23.55万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 1996-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2265051
• 关键词: NMDA receptors; aminoacid inhibitor; caudate nucleus; decerebration; deoxyglucose; electrophysiology; glucose metabolism; glutamate receptor; heat stimulus; local anesthetics; neural information processing; neurophysiology; pain; periaqueductal gray matter; radiotracer; sciatic nerve; single cell analysis; spinal cord; spinal nerves

The long term goal of this research project is to characterize spinal cord spatial and temporal neural mechanisms that encode information related to acute and chronic pain. Progress during the last 3 years of this project has resulted in evidence that both spatial recruitment and impulse frequencies in spinal nociceptive neurons are likely to be critical factors in encoding nociceptive stimulus intensity as well as in encoding the distinction between non-nociceptive and nociceptive somatosensory events. The proposed continuation of these efforts will rely on the utilization of [14C]-2-deoxyglucose mapping procedures and electrophysiological recordings from dorsal horn nociceptive neurons to accomplish 7 SpecifiC aims: (1) To provide electrophysiological mapping of L2 to L5 neural activity under stimulus conditions used in the [14C]-2- deoxyglucose experiments so as to provide functional interpretations of our results with metabolic imaging analysis; (2) To more precisely delineate the rostral-caudal extent of elevated neural activity elicited by graded nociceptive thermal stimuli; (3) To determine the similarities and differences in the rat spinal cord of spatial patterns of elevated neural activity in response to nociceptive stimulation in spinalized, decerebrate, and intact preparations; (4) To determine how spatial recruitment and/or integration at the level of single spinal cord nociceptive neurons Can account for spatial summation of heat induced pain; (5) To compare the patterns of [14C]-2-deoxyglucose activity within the spinal cord across two types of nociceptive stimuli: thermal stimulation (45 degrees-49 degrees C) and formalin injection into the foot and to relate such patterns of activity with areas of spinal gray matter (at cervical levels and contralateral dorsal horn regions) known to be either inhibited or excited by the types of stimuli to be used ; (6) To further examine the spatial patterns of elevated neural activity in the spinal cords of rats experiencing experimental painful peripheral mononeuropathy and to compare such patterns with electrophysiological recordings of neural activity from L2 to L5; (7) To examine the effects of antagonists of the glutamate/aspartate receptor and local anesthetic agents on behavioral indexes of pain and spatial distributions of elevated neural activity within spinal cords of rats with a painful mononeuropathy. The results of this proposed work will provide an extensive characterization of the role of spatial and temporal factors in encoding nociceptive information under both acute and pathophysiological conditions. Finally, the analysis of pharmacological interventions on spatial recruitment and on abnormal pain-related behavior in a model of neuropathic pain may be helpful in providing new therapeutic approaches to treat neuropathic pain and perhaps other chronic pain disorders in man.

该研究项目的长期目标是表征脊髓 编码与有关信息有关的空间和时间神经机制 急性和慢性疼痛。在该项目的最后三年中进展 有证据表明空间招募和冲动 脊柱伤害性神经元中的频率可能很关键 编码伤害性刺激强度以及编码的因素 非伤害性和伤害性体感之间的区别 事件。这些努力的拟议延续将依靠 利用[14C] -2-脱氧葡萄糖映射程序和 从背角伤害神经元到的电生理记录到 完成7个具体目的：（1）提供的电生理映射 在[14C] -2-中使用的刺激条件下的L2至L5神经活动 脱氧葡萄糖实验，以提供 我们通过代谢成像分析的结果； （2）更精确 引起神经活动的升高的延髓审计范围 通过分级伤害性热刺激； （3）确定相似之处 和高架空间模式的大鼠脊髓差异 神经活动响应于脊柱刺激的伤害感受性刺激 杂交和完整的制剂； （4）确定如何空间 在单脊髓的水平上招募和/或集成 伤害性神经元可以解释热诱导的空间总和 疼痛; （5）比较[14C] -2-脱氧葡萄糖活性的模式 两种类型的伤害感受刺激的脊髓：热 刺激（45度-49度c）和福尔马林注入脚 并将这种活动模式与脊柱灰质区域联系起来 （在宫颈水平和对侧背角区域）已知为 要么被要使用的刺激类型抑制或激发； （6）至 进一步研究神经活动升高的空间模式 大鼠的脊髓经历了实验性疼痛的周围 单肌病并将此类模式与电生理学进行比较 L2到L5的神经活动的记录； （7）检查 谷氨酸/天冬氨酸受体和局部麻醉的拮抗剂 对疼痛行为指数和升高的空间分布的代理 大鼠脊髓内的神经活动，具有疼痛的单肌病。 这项拟议工作的结果将提供广泛的 空间和时间因素在编码中的作用的表征 急性和病理生理学下的伤害性信息 状况。最后，对药理学干预的分析 在一个模型中 神经性疼痛可能有助于提供新的治疗方法 治疗人类的神经性疼痛以及其他慢性疼痛障碍。