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ONTOGENY OF NEUROCHEMICAL MECHANISMS OF PAIN REACTIVITY

疼痛反应的神经化学机制的个体发生

基本信息

批准号：
6402839
负责人：
TAMARA E KING
金额：
$ 4.38万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-06-01 至
项目状态：
未结题

项目摘要

DESCRIPTION Infants are capable of responding to painful stimulation, however, these responses and the physiological mechanisms mediating these responses continue to develop after birth. The experiments proposed here examine changes observed in the neurokinin and glutamate neurotransmitter systems, which are involved in the pain responses of adult animals. Mice lacking the NK1 receptor (NK1 knockout), mice lacking the neuropeptides neurokinin-A and substance P (preprotachykinin-A knockout), and wildtype controls are tested for responsivity on acute and tonic pain, allodynia and hyperalgesia to determine the functional role of the neurokinin system across development. Involvement of the glutamate NMDA receptor in pain reactivity across development is also examined by intrathecal administration of MK-801, an NMDA receptor antagonist, in wildtype animals. The development of the interaction between the neurokinin neurotransmitter system is characterized by assessing the effect of intrathecal administration of MK-801 in NK1 knockout and preprotachykinin-A knockout mice. Alterations in the synthesis and expression of neurokinin, CGRP, and glutamate peptides and receptors in the knockout mice are assessed across development using in situ hybridization and immunocytochemistry. Understanding changes in the neurotransmitter systems across development is important in understanding the pain response, and treatment of pain in infants.

描述婴儿能够对疼痛刺激做出反应，然而，这些反应和介导这些反应的生理机制在出生后继续发展。这里提出的实验检查了神经激肽和谷氨酸神经递质系统中观察到的变化，这些变化与成年动物的疼痛反应有关。测试缺乏 NK1 受体（NK1 敲除）的小鼠、缺乏神经肽神经激肽-A 和 P 物质（前原速激肽-A 敲除）的小鼠以及野生型对照小鼠对急性和强直性疼痛、异常性疼痛和痛觉过敏的反应性，以确定神经激肽系统在整个发育过程中的功能作用。还通过在野生型动物中鞘内注射 MK-801（一种 NMDA 受体拮抗剂）来检查谷氨酸 NMDA 受体在整个发育过程中参与疼痛反应的情况。通过评估 NK1 敲除小鼠和前原速激肽-A 敲除小鼠鞘内注射 MK-801 的效果来表征神经激肽神经递质系统之间相互作用的发展。使用原位杂交和免疫细胞化学来评估基因敲除小鼠中神经激肽、CGRP 和谷氨酸肽和受体的合成和表达的变化。了解神经递质系统在发育过程中的变化对于了解婴儿的疼痛反应和疼痛治疗非常重要。