MECHANISMS OF SYMPTOMS IN NEUROPATHIC PAIN & RSD

假设和具体目标集中在两组不同条件的病理生理学。 第一类是直立不耐受，特别是体位性心动过速综合征（POTS）。 第二类是神经性疼痛。 对神经性疼痛的研究已经被组织成两种类型的疼痛，一种是对正常非疼痛刺激的反应（异常性疼痛），另一种是对反射性交感神经营养不良之谜的反应。 异常性疼痛是对轻触（动态异常性疼痛）和压力（静态异常性疼痛）的反应。主要假设是POTS患者发生病毒感染后，可能是免疫介导的长度依赖性自主神经病变，继发性脑干机制随之发生，导致肾上腺素能亢进状态。 我们将评估直立性不耐受的病理生理学，使用显微神经摄影记录与姿势性心动过速综合征（POTS）患者和对照组的腓神经的肌肉交感神经活动。 我们将专门评估静息肌交感神经活动是否增加（由于中枢驱动增加）或减少（由于去神经支配），并评估varoflex反应性，是否对直立性应激和诱导的血压变化的反应受损。对具有动态机械异常性疼痛的神经性疼痛患者进行研究的假设是，低阈值机械感受器初级传入将神经冲动传播到中枢神经系统，并导致具有动态机械异常性疼痛的疼痛体验。 本研究将确定外周神经源性疼痛和动态机械异常性疼痛患者的单一低阈值机械感受器初级传入的快速重复神经内微刺激是否会导致疼痛作为具有电刺激阈值强度（受试者报告感知感觉的最低强度）的第一感知感觉。

The hypothesis and specific aims are focused on the pathophysiology of two different groups of conditions. The first group is orthostatic intolerance, specifically the postural tachycardia syndrome (POTS). The second group is neuropathic pain. The studies on neuropathic pain have been organized into 2 types of painfulness in response to a normally non-painful stimulus (allodynia) and to the enigma of reflex symmpathetic dystrophy. The allodynias are in response to light touch (dynamic allodynia) and to pressure (static allodynia). The primary hypothesis is that patients with POTS develop a post-viral, presumably immune-mediated length-dependent autonomic neuropathy and that secondary brain-stem mechanisms supervene, resulting in a hyperadrenergic state. We will evaluate the pathophysiology of orthostatic intolerance using microneurographic recordings of muscle sympathetic nerve activity from peroneal nerves of patients with the postural tachycardia syndrome (POTS) and controls. We will specifically evaluate if resting muscle sympathetic nerve activity is increased (due t increased central drive) or reduced (due to denervation) and, to evaluate varoflex responsiveness, if the response to orthostatic stress and to induced blood pressure alterations are impaired. The hypothesis for the study of patients with neuropathic pain who have dynamic mechanical allodynia is that low threshold mechanoreceptor primary afferents propagate neural impulses to the central nervous system and result in the experience of pain with dynamic mechanical allodynia. The study will determine if rapid repetitive intraneural microstimulation of single low threshold mechanoreceptor primary afferents in patients with peripheral neurogenic pain and dynamic mechanical allodynia causes pain as the first perceived sensation with liminal intensity (the lowest intensity at which the subjects reports a perceived sensation) of electrical stimulation.