PAIN AND HYPERALGESIA--MICRONEUROGRAPHY IN PATIENTS

慢性神经病理性疼痛的异常神经机制 将在患者身上探索痛觉过敏，利用一系列新的 严格的神经生理学技术现在可用于人体研究和 在我们实验室使用中。建议的实验结果如下 期望提高诊断和管理的科学基础 这些患者中的许多人目前都经历了不良的临床 调查或者接受无效治疗的。 该实验计划将检验以下假设： 1.异常敏感(或感觉兴奋)的初级活动 伤害性感受器是自发疼痛和痛觉过敏的基础。 2.低阈值有髓机械感受器的活动异常兴奋 敏感的脊髓神经元可引起自发性疼痛和痛觉过敏。 3.低阈值兴奋的交感传出活动 初级机械感受器或敏化的伤害性感受器，触发异常 自发性疼痛和痛觉过敏的机制。 这些以科学为基础的假说现在可以直接在 患者，消除了从动物推断结果的必要性 研究。 同意的患者，亲自检查并通过我们的 神经感觉单位，将接受定量感觉测试和 对照实验引入前后的显微神经学检查 变量旨在：a)自然地或电地选择性地激活， 初级感觉单位的亚群；b)选择性地、机械地阻断 或药理上，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)药理上阻断全部或部分 感同身受的流出。 从我们的初步研究中得出的结果预示着巨大的收益 从基础科学和应用层面的这项研究。

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.