Primary Afferent Sensitization in Postoperative Pain

术后疼痛的初级传入敏化

• 批准号: 6598701
• 负责人: TIMOTHY JOHN BRENNAN
• 金额: $ 28.75万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6598701
• 关键词: behavior test; electrophysiology; gene targeting; genetically modified animals; hydrogen ions; hyperalgesia; laboratory rat; lactates; nerve growth factors; neurophysiology; nociceptors; pain; polymerase chain reaction; postoperative complications; receptor; sodium channel; southern blotting

DESCRIPTION (provided by applicant): Postoperative, incisional pain is a unique but common form of acute pain. Since effective postoperative analgesia reduces morbidity following surgery, new treatments continue to be investigated. The proposal is dedicated toward studies of the mechanisms that subserve acute postoperative pain. It is through the study of mechanisms that a better understanding of incisional pain can be achieved and new treatments can be advanced. The work proposed will specifically characterize the mechanisms for incisional pain at the primary afferent nerve terminal. Neurophysiologic, biochemical, and molecular approaches will be used in concert to examine the mechanisms that contribute to activation and sensitization of nociceptive afferent fibers and subsequent primary hyperalgesia. Our working hypothesis is that 1) nociceptors responding to heat develop background activity and heat sensitization after incision. This sensitization is caused by H+ ions and NGF increased by the incision acting on VR1 receptors contributing to heat hyperalgesia and nonevoked pain behaviors. VR1 activation does not influence behaviors indicating mechanical hyperalgesia. 2) MIAs are activated by incision and develop mechanosensitivity. H+ ions and lactate increased by incision activate ASIC channels contributing to mechanical hyperalgesia. Incision-induced changes in expression of receptors activated by low pH will be measured. These data will determine the particular afferents sensitized by incision and the role of receptors activated by decreased tissue pH on pain behaviors caused by the incision. The proposed experiments will advance our understanding of postoperative incisional pain and provide a basis for rationale design of new pharmacologic treatment modalities.

描述（由申请人提供）： 术后，切口疼痛是一种独特但常见的急性疼痛形式。由于有效的术后镇痛可降低手术后的发病率，因此不断研究新的治疗方法。该提案致力于研究促进术后急性疼痛的机制。通过研究机制，可以更好地了解切口疼痛并推进新的治疗方法。拟议的工作将具体描述初级传入神经末梢切口疼痛的机制。将联合使用神经生理学、生物化学和分子方法来检查有助于伤害性传入纤维的激活和敏化以及随后的原发性痛觉过敏的机制。我们的工作假设是：1）对热做出反应的伤害感受器在切口后会产生背景活动和热敏化。这种敏化是由作用于 VR1 受体的切口增加的 H+ 离子和 NGF 引起的，从而导致热痛觉过敏和非诱发性疼痛行为。 VR1 激活不会影响机械痛觉过敏的行为。 2) MIA 通过切口激活并产生机械敏感性。切口增加的 H+ 离子和乳酸激活 ASIC 通道，导致机械痛觉过敏。将测量由低pH激活的切口诱导的受体表达的变化。这些数据将确定切口敏感的特定传入神经，以及组织 pH 值降低激活的受体对切口引起的疼痛行为的作用。所提出的实验将增进我们对术后切口疼痛的理解，并为新的药物治疗方式的合理设计提供基础。