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上。第一组是直立性不耐受，特别是体位性心动过速综合征（POTS）。第二组是神经性疼痛。神经性疼痛的研究被分为两种类型的疼痛，一种是对正常情况下非疼痛性刺激（异常性疼痛）的反应，另一种是对反射性交感神经营养不良之谜的反应。异位性疼痛是对轻触（动态异位性疼痛）和压力（静态异位性疼痛）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，继发性脑干机制发生，导致肾上腺素能亢进状态。我们将通过对体位性心动过速综合征（POTS）患者和对照组的腓神经肌肉交感神经活动的微神经记录来评估直立性不耐受的病理生理学。我们将特别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），并评估对直立应激和诱导血压改变的反应是否受损。对伴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神经将神经冲动传递到中枢神经系统，从而导致伴有动态机械异常性疼痛的疼痛体验。该研究将确定，对于周围神经源性疼痛和动态机械异常性疼痛患者，单一低阈值机械受体初级传入神经的快速重复神经内微刺激是否会导致疼痛作为电刺激阈值强度（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.