ONTOGENY OF NEUROCHEMICAL MECHANISMS OF PAIN REACTIVITY

描述婴儿能够对痛苦的刺激做出反应，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。这里提出的实验检查了观察到的神经激肽和谷氨酸神经递质系统的变化，这两个系统与成年动物的疼痛反应有关。缺乏NK1受体(NK1基因敲除)的小鼠，缺乏神经肽神经激动素-A和P物质(原激动素-A前基因敲除)的小鼠，以及野生型对照小鼠，被测试对急性和紧张性疼痛、超敏和痛觉过敏的反应性，以确定神经激肽系统在发育过程中的功能作用。还通过鞘内注射NMDA受体拮抗剂MK-801，在野生型动物中研究了谷氨酸NMDA受体在整个发育过程中对疼痛反应的参与。神经激肽神经递质系统之间相互作用的发展是通过评估鞘内注射MK-801对NK1基因敲除和前速激肽-A基因敲除小鼠的影响来表征的。用原位杂交和免疫细胞化学方法评估了基因敲除小鼠在发育过程中神经激肽、降钙素基因相关肽和谷氨酸多肽及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了解婴儿的疼痛反应和疼痛的治疗非常重要。

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.