SEROTONERGIC CONTROL OF SPINAL CORD NEUROTRANSMISSION

脊髓神经传递的血清素控制

• 批准号: 2685612
• 负责人: PETER A GOLDSTEIN
• 金额: $ 9.53万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2685612
• 关键词: NMDA receptors; action potentials; calcium flux; calcium indicator; calcium ion; charge coupled device camera; digital imaging; dorsal horn; excitatory aminoacid; fluorescence microscopy; glutamates; laboratory rat; neural transmission; neurons; neuroregulation; neurotransmitter agonist; pain; sensory receptors; serotonin; serotonin inhibitor; serotonin receptor; spinal cord; synapses; tissue /cell culture; voltage /patch clamp; voltage gated channel

The long-term objective of this grant is to further understand the cellular mechanisms underlying the pathophysiology of both acute and chronic pain states. The neurophysiological mechanisms underlying the transmission and processing of nociceptive, or painful, stimuli within the central nervous system remain poorly understood. Multiple neurotransmitter system are thought to be involved in the transmission of pain signals, including but not limited to those mediated by glutamate and serotonin (5- HT). Although substantial evidence exists implicating glutamate as the principle neurotransmitter responsible for excitatory transmission, the direct and.or regulatory effects of the 5-HT system on the glutamatergic system are well defined. The overall purpose of this project is to help further define the interactions between the glutamatergic and 5-HT transmitter systems in the spinal chord so as to obtain a clearer understanding of the processes that regulate nociceptive afferent neurotransmission. To investigate how glutamatergic neurotransmission is regulated by 5-HT, an in vitro preparation will be used. Pre-synaptic stimulation is achieved by stimulating the dorsal root and post-synaptic whole-cell recordings are made from visually identified single neurons in the substantia gelatinosa using the patch clamp technique. Briefly, a thin transverse section of spinal cord with dorsal roots attached is obtained from post-natal rat pup. The spinal cord slice is then superfused in an extracellular bath solution containing selective agonists and antagonists for specific 5-HT receptor subtypes while recording dorsal root-evoked post-synaptic events. Proceeding in this manner will enable us to identify which 5-HT receptor subtypes modulate glutamatergic transmission. Once the receptor subtypes are identified, the site(s) of action, pre-and/or post-synaptic, will be identified. The results will hopefully provide new insights into the mechanisms of pain transmission as well as suggest novel methods for providing analgesia in both the acute and chronic setting.

这笔赠款的长期目标是进一步了解 急性和 慢性疼痛状态。神经生理机制 伤害感受性或痛苦的刺激的传播和处理 中枢神经系统的理解仍然很差。多个神经递质 人们认为系统参与疼痛信号的传播， 包括但不限于谷氨酸和5-羟色胺介导的那些（5- HT）。尽管存在大量证据，这意味着谷氨酸 负责兴奋性传播的主要神经递质， 直接和。或5-HT系统对谷氨酸能的调节作用 系统定义很好。该项目的总体目的是帮助 进一步定义谷氨酸能和5-HT之间的相互作用 脊柱和弦中的发射器系统，以获得更清晰的 了解调节伤害感染传入的过程 神经传递。 调查谷氨酸能神经传递如何受到5-HT的调节， 将使用体外制剂。实现突触前刺激 通过刺激背根和突触后的全细胞记录是 用视觉识别的单神经元制成明胶中的单个神经元 使用斑块夹技术。简而言之 带有背根的脊髓是从产后大鼠获得的 小狗。然后将脊髓切片超过细胞外浴 含有特定5-HT的选择性激动剂和拮抗剂的溶液 受体亚型在记录背根引起的突触后事件时。 以这种方式进行，使我们能够确定哪个5-HT受体 亚型调节谷氨酸能传播。一旦受体亚型 确定，前和​​/或突触后的动作部位将是 确定。 结果有望提供有关机制机制的新见解 疼痛传播以及建议提供镇痛的新方法 在急性和慢性环境中。