TRPA1 in Postoperative Pain

TRPA1 在术后疼痛中的作用

基本信息

  • 批准号:
    9362101
  • 负责人:
  • 金额:
    $ 29.36万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-09-01 至 2021-08-31
  • 项目状态:
    已结题

项目摘要

Project Summary Management of acute postoperative pain is an essential component of perioperative patient care. Despite a heightened awareness and increased efforts, pain after surgery continues to be a significant clinical problem. The long-term goal of this proposal is to identify novel targets for developing effective non-opioid treatments that can greatly reduce pain after surgery. The overall objective of this proposal is to understand the peripheral mechanisms by which muscle injury, in the course of surgery, activates and sensitizes nociceptive pathways, thereby leading to pain after surgery. The central hypothesis is that sustained pain-related behaviors after muscle injury are in part mediated by TRPA1 and its endogenous ligands in deep tissue. The rationale for the proposed research is that a better understanding of the mechanisms and origin of pain after surgery will allow us to develop new and innovative strategies for effective postoperative pain management. To accomplish the overall objective, the following specific aims are proposed: Aim 1. Establish the role of TRPA1 in muscle injury-related pain behaviors, in rodent models of surgery. The working hypothesis is that pharmacological or genetic inhibition of TRPA1 decreases ongoing, spontaneous pain behaviors and pain with activities that result from by muscle injury during surgery. Aim 2. Examine the effects of tissue injury by surgery on the production of endogenous TRPA1 ligands in the incised muscle environment. The working hypothesis of this aim is that endogenous TRPA1 ligands, such as reactive oxygen species and 4- hydroxynonenal, are increased in the wound environment after incision, contributing to activation of nociceptors via TRPA1. Aim 3. Define the role of TRPA1 in surgery-induced sensitization of muscle nociceptors. The working hypothesis of this aim is that nociceptors innervating incised muscle have greater responsiveness to TRPA1 ligands, compared to nociceptors innervating un-injured muscle. It is expected that the proposed research will demonstrate that endogenous TRPA1 ligands and the TRPA1 receptor are responsible for strong activation and sensitization of nociceptive pathways by incision of deep muscle tissues. These results will have an important positive impact, by identifying novel targets for improved treatment of postoperative pain, as well as greatly advancing our knowledge in the field of pain research.
项目摘要 急性术后疼痛的管理是围手术期患者的重要组成部分 在乎尽管提高了认识并加大了努力,但手术后的疼痛仍在继续 是一个重要的临床问题。该提案的长期目标是确定新的 开发有效的非阿片类药物治疗的目标,可以大大减少疼痛后, 手术本提案的总体目标是了解外围机制 在手术过程中,肌肉损伤通过其激活并敏化伤害感受性, 导致手术后疼痛。核心假设是, 肌肉损伤后的疼痛相关行为部分由TRPA1及其受体介导。 深部组织中的内源性配体。拟议研究的基本原理是, 了解手术后疼痛的机制和起源将使我们能够开发 有效的术后疼痛管理的新的和创新的策略。完成 在总体目标方面,提出了以下具体目标:目标1。确立...的作用 TRPA1在啮齿动物手术模型中与肌肉损伤相关的疼痛行为。工作 假设是TRPA 1的药理学或遗传抑制持续降低, 自发性疼痛行为和疼痛与活动所造成的肌肉损伤, 手术目标二。检查手术造成的组织损伤对生产的影响 内源性TRPA1配体在切割的肌肉环境。的工作假设 这一目的是内源性TRPA 1配体,如活性氧和4- 羟基壬烯醛在切口后的伤口环境中增加, 通过TRPA1激活伤害感受器。目标3。定义TRPA1在手术诱导的 肌肉伤害感受器的敏感化。这一目标的工作假设是, 支配切割的肌肉对TRPA 1配体的反应性更高, 支配未受伤肌肉的伤害感受器。预计拟议的研究将 证明内源性TRPA1配体和TRPA1受体负责 深部肌肉切开对伤害性感受通路的强烈激活和敏化 组织中通过确定新的目标,这些结果将产生重要的积极影响 改善术后疼痛的治疗,以及大大提高我们的知识, 疼痛研究领域。

项目成果

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