Periaqueductal Gray in Pain Modulatory Circuitry

尽管最近的技术进步，实现充分的疼痛管理继续挑战护士和疼痛继续治疗不足。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检验以下假设：脑干部位内的神经化学和神经元激活参与持续性炎症和痛觉过敏后的伤害感受变化的下行调制，并且腹外侧PAG（vlPAG）在这些变化中起关键作用。该假设将在持续性炎症的大鼠模型中进行测试。将在炎症后的三个时间点（0、3和24小时）研究具有化学消融或完整vlPAG的两组大鼠。预计，使用神经化学物质和Fos蛋白的抗体，在炎症之前和之后将看到差异。此外，所提出的实验将使申请人能够评估vlPAG在这些变化中的作用。这项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，并将进一步开发未来的治疗方法。

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.