PAINFUL SMALL CALIBER FIBER NEUROPATHY IN AGING HUMANS

在晚年，正常人可能会受到 涉及小口径神经纤维的年龄相关性周围神经病变， 产生复杂的、致残的、痛苦的综合症。通过系统 专业临床方法的应用（定量心理物理学 感觉测试，温度记录和自主测试），我们已经确定了两个 不同的亚综合征：a）患者的“燃烧”的脚和腿， 客观上热并且随着冷却而改善，以及，B）逆转患者的成像 肢体“灼热”，客观上是寒冷的，并随着冷却而恶化 （Ochoa，1989年b）。 在明显周围神经病变患者中， 现象，初步调查结合专业临床试验 用实验性选择性神经纤维阻滞， 显微记录和活检神经的定量形态测量表明， “热”综合征是由无髓鞘C 伤害感受器（疼痛）感觉单位（Cline，Ochoa & Torebjork，1989）。这 患者中描述的“热”综合征在 急性辣椒素诱发的实验性神经源性炎症 应用（Culp，Ochoa，Cline & Dotson，1989）。“冷”综合症可能 具有相关的病理生理学或可能反映了典型的中枢释放 冷特异性传入纤维损伤引起的C伤害性感受器传入现象 （Yamitsky & Ochoa，1989年a）。 本文提出的研究的主要目标是进一步表征 疼痛性晚期神经病的临床现象学，并测试 一系列具体的假设，关于病理生理学基础， 痛苦的综合症。实验的目的是为了测试可能存在的 a）致敏的伤害感受器，B）逆行性神经源性炎症，c） 与交感传出神经有关的各种血管收缩模式 活动或去神经支配，和，d）原发性疼痛的中枢去抑制 由于释放机制的输入。局部伤害感受器敏化和 脱敏将通过特定的神经毒素产生，例如 辣椒素，以测试疼痛和血管现象的病理生理学， 预测潜在的治疗结果（Simone等人，1989）。 最终的目标是真正治疗疼痛的综合症， C伤害感受器单位的活性，这些单位在功能上与 皮肤感受器这将通过废除 主要是夸大或中枢解除抑制的感觉输入，从第一 通过伤害感受器脱敏来排列疼痛神经元。

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.