Periaqueductal Gray in Pain Modulatory Circuitry

尽管最近技术取得了进步，但实现适当的疼痛管理仍然是护士面临的挑战，疼痛仍然得不到充分治疗。该项目的主要目标是增加对身体内源性疼痛控制机制的理解，并期望开发更有效的治疗策略。该建议的具体目的是验证脑干部位的神经化学和神经元激活参与持续炎症和痛觉过敏后的下行调节的假设，以及腹侧PAG （vlPAG）在这些变化中起关键作用。这一假设将在持续炎症的大鼠模型中得到验证。两组大鼠，化学消融或完整的vlPAG，将在炎症后的三个时间点进行研究；0,3和24小时。预计，使用神经化学物质和Fos蛋白抗体，将看到炎症前后的差异。此外，拟议的实验将使申请人能够评估vlPAG在这些变化中的作用。本研究将为申请人提供研究内源性疼痛机制所需的各种研究技术，并将进一步发展未来的治疗领域。

Despite recent advances in technology, achieving adequate pain management continues to challenge nurses and pain continues to be undertreated. The primary goal of this project is to increase understanding of the body's endogenous mechanisms of pain control, with anticipation of developing more efficacious treatment strategies. The specific aim of this proposal is to test the hypothesis that neurochemistry and neuronal activation within brainstem sites involved in descending modulation of nociception change over time following persistent inflammation and hyperalgesia and that the ventrolateral PAG (vlPAG) plays a key role in these changes. This hypothesis will be tested in a rat model of persistent inflammation. Two groups of rats, either with a chemical ablation of or an intact vlPAG, will be studied at three time points following inflammation; 0, 3, and 24 hours. It is anticipated that, using antibodies to neurochemicals and Fos protein, differences will be seen prior to and following inflammation. Moreover, the proposed experiments will enable the applicant to assess the role of the vlPAG in these changes. This study will provide the applicant with a variety of research techniques necessary to study endogenous pain mechanisms and will further the field in developing future treatments.