PAINFUL SMALL CALIBER FIBER NEUROPATHY IN AGING HUMANS

在晚年，正常人可能会受到一种 涉及小口径神经纤维的年龄相关性周围神经病， 产生复杂的、致残的、痛苦的症状。通过系统化 专门化临床方法的应用(定量心理物理 感官测试、热像仪和自主神经测试)，我们已经确定了两个 不同的亚型：a)脚和腿“灼热”的患者 客观上炎热，并随着降温而改善，以及，b)颠倒患者的形象 “灼伤”的四肢客观上是寒冷的，并随着降温而恶化 (奥乔亚，1989b)。 在表现出类似感觉的临床周围神经病患者中 现象，结合专业临床测试的初步调查 实验性选择性神经纤维阻滞，神经内 显微记录和活检神经的定量形态测量表明， “热”证是无髓鞘C细胞致敏的结果 伤害感受器(疼痛)感觉单位(Cline，Ochoa&Torebjork，1989)。这 在患者身上所描绘的“热”综合征在 急性辣椒素诱导的实验性神经源性炎症 应用(Culp，Ochoa，Cline&Dotson，1989)。“感冒”综合症可能 有相关的病理生理学或可能反映了典型的中枢释放 冷特异性传入损伤引起的C-伤害性感受器传入现象 (Yamitsky&Ochoa，1989a)。 这里提出的研究的主要目标是进一步描述 痛性老年神经病的临床现象学研究 一系列关于脑血管疾病病理生理学基础的具体假说 痛苦的症状。实验的设计是为了测试可能的存在 A)致敏的伤害性感受器，b)反向神经源性炎症，c) 与交感神经传出相关的多种血管收缩模式 活动或去神经，以及，d)中枢性去抑制原发疼痛 由于释放机构的输入。局部伤害性感受器敏化和 脱敏是通过特定的神经毒素产生的，例如 辣椒素，以测试疼痛和血管现象的病理生理学，以及 以预测潜在的治疗结果(Simone等人，1989)。 一个最终的目标是真正地治疗由 功能上保持连接的C伤害性感受器单元中的活动 皮肤感受器。这将通过废除这两项中的任何一项来尝试 主要是夸张的或中央不受限制的感觉输入 通过伤害性感受器脱敏对痛觉神经元进行排序。

In late life, otherwise normal individuals may be afflicted by an age-related peripheral neuropathy that involves small caliber nerve fibers, producing complex, crippling, painful syndromes. Through systematic application of specialized clinical methods (quantitative psychophysical sensory tests, thermography, and autonomic testing), we have identified two distinct subsyndromes: a) patients with "burning" feet and legs which are objectively hot and improve with cooling, and, b) reverse image patients with "burning" limbs which are objectively cold and worsen with cooling (Ochoa, 1989b). In patients with overt peripheral neuropathy expressing comparable sensory phenomena, preliminary investigation combining specialized clinical tests with experimental selective nerve fiber blocks, intraneural microrecordings, and quantitative morphometry of biopsied nerves, indicates that the "hot" syndrome results from sensitization of unmyelinated C nociceptor (pain) sensory units (Cline, Ochoa & Torebjork, 1989). This "hot" syndrome as delineated in patients is completely replicated during experimental neurogenic inflammation elicited by acute capsaicin application (Culp, Ochoa, Cline & Dotson, 1989). The "cold" syndrome might have related pathophysiology or may reflect a classic central release phenomenon of C nociceptor input due to damage of cold-specific afferents (Yamitsky & Ochoa, 1989a). The primary goals of the research proposed here are to further characterize the clinical phenomenology in painful late life neuropathy and to test a series of specific hypotheses concerning the pathophysiological basis for the painful syndromes. Experiments are designed to test possible existence of a) sensitized nociceptors, b) antidromic neurogenic inflammation, c) various patterns of vasoconstriction related to sympathetic efferent activity or denervation, and, d) central disinhibition of primary pain input due to release mechanisms. Local nociceptor sensitization and desensitization will be produced by means of specific neurotoxins, such as capsaicin, to test pathophysiology of the pains and vascular phenomena, and to predict potential therapeutic outcome (Simone, et al, 1989). An ultimate goal is to actually treat painful syndromes emanating from activity in C nociceptor units which remain functionally connected to cutaneous receptors. This will be attempted through abolition of either primarily exaggerated or centrally disinhibited sensory input from first order pain neurons by nociceptor desensitization.