PAIN AND HYPERALGESIA--MICRONEUROGRAPHY IN PATIENTS

慢性神经病理性疼痛背后的异常神经机制 将利用一系列新颖的方法在患者中探索痛觉过敏 严格的神经生理学技术现在可用于人类研究和 在我们实验室使用。 拟议实验的结果是 有望提高诊断和管理的科学基础 这些患者中，许多人目前正在接受考虑不周的临床治疗 调查或接受无效治疗。 实验计划将检验以下假设： 1. 异常敏感（或兴奋）初级活动 伤害感受器是自发疼痛和痛觉过敏的基础。 2. 低阈值有髓鞘机械感受器的活动异常兴奋 敏感的脊髓神经元引起自发性疼痛和痛觉过敏。 3. 交感传出活动，通过低阈值的兴奋 初级机械感受器或敏化伤害感受器，引发异常 导致自发性疼痛和痛觉过敏的机制。 这些基于科学的假设现在可以直接进行测试 患者，消除了从动物推断结果的必要性 研究。 同意的患者，经过我们的亲自检查和预选 神经感觉单元，将进行定量感觉测试和 在引入受控实验之前和期间的显微神经造影 变量旨在：a）选择性地自然或电动激活， 初级感觉单位的亚群； b) 选择性地机械地阻止 或药理学上的初级传入纤维亚群； c) 选择性地兴奋或抑制交感神经亚群 传出神经元； d) 在药理学上阻断全部或部分 同情心流出。 我们的初步研究结果有望带来显着的收益 来自基础科学和应用层面的研究。

Abnormal neuronal mechanisms underlying chronic neuropathic pain and hyperalgesia will be explored in patients, making use of a novel array of rigorous neurophysiological techniques now available for human studies and in use in our laboratory. Results from the proposed experiments are expected to improve the scientific foundation for diagnosis and management of these patients, many of whom presently undergo ill conceived clinical investigation or receive ineffectual treatment. The experimental plan will test the following hypotheses: 1. Activity in abnormally sensitive (or ephaptically excited) primary nociceptors underlies spontaneous pain and hyperalgesia. 2. Activity in low-threshold myelinated mechanoreceptors excites abnormally sensitive spinal neurons to cause the spontaneous pain and hyperalgesia. 3. Sympathetic efferent activity, through excitation of low-threshold primary mechanoreceptors or sensitized nociceptors, triggers the abnormal mechanisms responsible for spontaneous pain and hyperalgesia. These scientifically based hypotheses are now amenable to direct testing in patients, eliminating the necessity of extrapolating results from animal research. Consenting patients, personally examined and preselected through our Neurosensory Unit, will undergo quantitative sensory testing and microneurography before and during introduction of controlled experimental variables intended to: a) selectively activate, naturally or electrically, subpopulations of primary sensory units; b) selectively block, mechanically or pharmacologically, subpopulations of primary afferent fibers; c) selectively excite or depress, reflexly, subpopulations of sympathetic efferent neurons; d) block pharmacologically the whole or part of the sympathetic outflow. Results emerging from our preliminary studies promise significant yield from this research at both basic scientific and applied levels.