Oxytocin-mediated modulation of peripheral mechanical sensibility after injury

总结。 目前的提案解决了与催产素(Oxt)相关的基本神经生理学问题。 正常和神经损伤环境下的药理学和疼痛神经生物学。我们的目标是定义(A)OXT PK/PD 快速传导传入(A-纤维)与触觉(LTMR：低阈值机械感受器)的关系 伤害性反应(AHTMRs：A纤维高阈值机械感受器)，(B)研究L5 SNL在峰期的作用 损伤(L5)和未损伤(L4)传入的最大敏化(第2周)及OXT介导的调制 以及(C)OXT诱导的敏感性(L4)和兴奋性的调节之间的关系 (5)恢复后(8-12周)动物行为(正常或异常)。 我们的工作假说有两个部分：1)A纤维对损伤的反应(LTMR：脱敏和AHTMR： 敏化)对于外周介导的神经病状态的发展至关重要，以及2)oxt可以 解决这种状态，并通过将这些传入从异常兴奋性中解救出来来调节恢复。我们 预计这项研究将有助于理解OXT的生理效应，总体上 中枢效应可以通过OXT外周调制(与项目2的相互作用，Martin博士)来解释，以及 如何优化这些效应以治疗人类患者的疼痛(与项目3互动，Dr。 艾森纳赫)。

SUMMARY. The current proposal addresses fundamental neurophysiological questions related to oxytocin (OXT) pharmacology and pain neurobiology in normal and nerve injury settings. We aim to define (a) the OXT PK/PD relationships on fast-conducting afferents (A-fibers), both tactile (LTMRs: low threshold mechanoreceptors) and nociceptive (AHTMRs: A-fiber high threshold mechanoreceptors), (b) to study the effects of L5 SNL at the peak of maximal sensitization (week 2) on injured (L5) and uninjured (L4) afferents and the OXT-mediated modulation of these sensitization process and (c) to correlate the OXT-induced modulation of sensibility (L4) and excitability (L5) with the animal behavior (normal or abnormal) after recovery (weeks 8-12). Our working hypothesis has two parts: 1) that A-fibers response to injury (LTMR: desensitization and AHTMR: sensitization) is critical for the development of a peripheral mediated neuropathic state and 2) that OXT can resolve this state and modulate the recovery by rescuing these afferents from they abnormal excitability. We anticipate that this research will contribute to understanding the physiological effects of OXT, how much of overall central effects can be explained by the OXT peripheral modulation (interaction with Project 2, Dr. Martin), and how these effects can be optimized for the treatment of pain in human patients (interaction with Project 3, Dr. Eisenach).