MECHANISMS OF SYMPTOMS IN NEUROPATHIC PAIN & RSD

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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.