ONTOGENY OF NEUROCHEMICAL MECHANISMS OF PAIN REACTIVITY

疼痛反应的神经化学机制的个体发生

• 批准号: 6135943
• 负责人: TAMARA E KING
• 金额: $ 3.75万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6135943
• 关键词: NMDA receptors; behavior test; capsaicin; chronic pain; edema; fos protein; gene induction /repression; genetically modified animals; glutamates; growth /development; heat stimulus; hyperalgesia; immunocytochemistry; in situ hybridization; inhibitor /antagonist; laboratory mouse; neurogenesis; newborn animals; pain; pain threshold; substance P; tachykinin

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.

婴儿能够对疼痛刺激做出反应，然而，这些反应和调节这些反应的生理机制在出生后继续发展。本文提出的实验研究了在神经激肽和谷氨酸神经递质系统中观察到的变化，这些系统与成年动物的疼痛反应有关。缺乏NK1受体（NK1敲除）的小鼠，缺乏神经肽neurokinin- a和P物质（proprotachykinin - a敲除）的小鼠，以及野生型对照，测试了对急性和强直性疼痛、异常性疼痛和痛觉过敏的反应，以确定神经激肽系统在整个发育过程中的功能作用。在野生型动物中，通过鞘内给药MK-801（一种NMDA受体拮抗剂）也检查了谷氨酸NMDA受体在整个发育过程中的疼痛反应性。通过评估鞘内给药MK-801对NK1敲除小鼠和proproachykinin - a敲除小鼠的影响，神经激肽-神经递质系统之间相互作用的发展。利用原位杂交和免疫细胞化学评估敲除小鼠中神经激肽、CGRP、谷氨酸肽和受体的合成和表达的变化。了解发育过程中神经递质系统的变化对于理解婴儿疼痛反应和疼痛治疗非常重要。