TRANSMITTER PHARMACOLOGY OF THE NEONATAL RAT SPINAL CORD

新生大鼠脊髓的递质药理学

• 批准号: 2420747
• 负责人: CHARLES M CONWAY
• 金额: $ 2.43万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2420747
• 关键词: afferent nerve; aging; calcitonin gene related peptide; developmental neurobiology; dorsal horn; high performance liquid chromatography; laboratory rat; neuropharmacology; neurotransmitter receptor; neurotransmitter transport; neurotransmitters; newborn animals; norepinephrine; pediatric pharmacology; radioimmunoassay; receptor binding; serotonin; substance P

Spinal pain processing mechanisms undergo dramatic changes during postnatal development and mature earlier at rostral than caudal spinal levels. This raises the possibility that the pharmacology of pain control in the neonatal chord may differ from that of the adult. Yet basic research is scarce regarding the developmental pharmacology of the spinal chord. The dorsal horn is an important site for study as it represents the location where spinal pain-transmitting (afferent peptide) and pain- modulating (bulbospinal monoamine) systems first converge. Given the maturational changes proceed rostro-caudally, independent analyses of rostral and caudal spinal levels (versus whole spinal chord) are required to avoid erroneous interpretation of developmental events. Consequently, these studies examine the developmental pharmacology of pain processing mechanisms in the spinal chord dorsal horn at cervical and lumbar spinal levels and employ a number of techniques including spinal slice perfusion, RIA, and HPLC. The specific aims target the cervical and lumbar enlargements and: 1) characterize maturational changes in dorsal horn transmitter levels of primary afferent substance P (SP) and calcitonin gene-related peptide (CGRP), and bulbospinal noradrenaline (NA) and serotonin (5-HT), 2) examine the evoked release of these neurotransmitters across age, 3) define the pharmacology of monoamine receptor systems that modulate the spinal release of SP and CGRP, and 4) study the development of the functional uptake and release of monamines by bulbospinal terminals. These studies will provide important new information about the developmental pharmacology of spinal pain processing and how they compare to those of the adult.

脊髓疼痛处理机制在治疗过程中发生了巨大的变化。 出生后的发育和成熟早于吻侧比尾侧脊髓 程度.这提出了一种可能性，即疼痛控制的药理学 在新生儿的弦可能不同于成人。但基本的 关于脊髓发育药理学的研究很少， 的和铉背角是一个重要的研究部位，因为它代表了 脊髓疼痛传递（传入肽）和疼痛- 调节（球脊髓单胺）系统首先会聚。鉴于 成熟的变化进行喙尾，独立的分析， 需要头侧和尾侧脊髓水平（相对于整个脊髓） 以避免对发育事件的错误解释。因此，委员会认为， 这些研究检查了疼痛处理的发育药理学 颈、腰段脊髓背角的机制 水平并采用许多技术，包括脊髓切片灌注， RIA和HPLC。具体目标是颈椎和腰椎 放大和：1）表征背角的成熟变化 初级传入P物质（SP）和降钙素的递质水平 基因相关肽（CGRP）和球脊髓去甲肾上腺素（NA）， 5-羟色胺（5-HT），2）检查这些神经递质的诱发释放 3）定义单胺受体系统的药理学， 调节脊髓SP和CGRP的释放; 4）研究脊髓损伤后 延髓脊髓神经元对单胺的功能性摄取和释放 terminals.这些研究将提供有关 脊髓疼痛处理的发育药理学及其比较 成年人的那些。