Pathophysiology and diagnosis of neurological pain syndromes

描述（由申请人提供）：组织损伤引起的疼痛通常是短暂的，并随着损伤愈合而消退。但是有些病人患有慢性疼痛，没有疾病或疼痛部位最近的损伤来解释它。这些“神秘疼痛”的病人得到我们的医疗保健系统的服务很差。他们中的许多人患有未被重视的神经疾病或损伤，如果我们有更好的测试，这些疾病或损伤可以被识别和治疗。候选人是一名医学博士，神经学家和神经科学家，在外周神经和疼痛方面进行研究和临床研究培训。她的长期职业目标是识别和研究神经性疼痛（神经痛）综合征，并开发更好的诊断和研究方法。神经痛，无论是由局灶性神经损伤还是糖尿病等疾病引起的，都与传递疼痛感觉和调节身体组织功能的小直径轴突（小纤维）的远端变性特别相关。小纤维损伤几乎不可能通过常规检查或测试（肌电图/神经传导研究）来诊断，因此许多慢性疼痛患者仍然没有诊断或有效治疗。候选人的近期职业目标是完成工作，证明损伤引起的局灶性神经痛患者在身体另一侧的“镜像”神经以及直接受伤的神经中存在轴突变性。研究职业发展计划包括建立新的多学科合作，以开发研究和诊断小纤维疾病的新方法。环境，马萨诸塞州总医院（MGH）在哈佛医学院，提供优秀的资源，合作者，和许多潜在的临床医生/研究人员实习生从居民和研究员。许多慢性疼痛患者在MGH寻求治疗，包括那些被转介到候选人的JCAHO认证的皮肤活检实验室诊断可疑的小纤维多发性神经病，为这个项目提供了另一个资源。在MGH，这样的患者有一个小的远端腿皮肤活检和免疫标记，以允许计数内的小纤维神经末梢。在Aim 1中，计划进行皮肤活检检测的患者还将接受下肢远端、激光多普勒、皮肤血流研究，以评估血流测量是否（以及哪些）可以提供皮肤活检检测的非侵入性替代品。在目标2中，将为这些相同的患者提供足跟骨密度的超声测试，以测试小纤维多发性神经病也会导致骨丢失的假设。如果这是真的，这些患者可能有目前未被认识到的骨质疏松症和骨折的风险。此外，调节小纤维对骨骼的影响可能为骨质疏松症提供潜在的新治疗方法。目标3涉及与MGH的神经放射学家合作，优化3特斯拉磁共振成像设备和方法，使医生能够看到慢性神经损伤，使一些患者在看似轻微或愈合的损伤后出现“神秘疼痛”。

DESCRIPTION (provided by applicant): Pain from tissue injury is usually brief and resolves as the injury heals. But some patients have chronic pain with no disease or recent injury in the painful area to explain it. These "mystery pain" patients are poorly served by our health care system. Many among them have unappreciated nerve diseases or injuries that could be recognized and treated if we had better tests. The candidate is an MD, PhD neurologist and neuroscientist with research and clinical fellowship training in peripheral nerve as well as pain. Her long-term career goals are to identify and investigate neuropathic pain (neuralgia) syndromes, and to develop better objective methods for diagnosing and studying them. Neuralgia, whether caused by focal nerve injuries or diseases such as diabetes, is specifically associated with distal degeneration of the small diameter axons (small-fibers) that transmit pain sensations and regulate the body's tissue functions. Small-fiber damage is nearly impossible to diagnose by routine examination or testing (electromyography/nerve conduction studies), so many chronic pain patients remain in limbo without a diagnosis or effective treatment. The candidate's immediate career goal is to finish work showing that patients with focal neuralgia caused by injury have axonal degeneration in "mirror" nerves on the opposite side of the body, as well as in nerves that were directly injured. The research career development plan includes establishing new multidisciplinary collaborations to develop new methods of studying and diagnosing small-fiber disease. The environment, Massachusetts General Hospital (MGH) at Harvard Medical School, provides outstanding resources, collaborators, and many potential clinician/investigator trainees from among the residents and fellows. The many chronic-pain patients seeking care at MGH, including those referred to the candidate's JCAHO-accredited skin biopsy laboratory for diagnosis of suspected small-fiber polyneuropathies, provide another resource for this project. At MGH such patients have a small distal-leg skin biopsy removed and immunolabeled to permit counting the small-fiber nerve endings within. In Aim 1 patients scheduled for such skin biopsy testing will also be offered distal-leg, laser-Doppler, skin-blood-flow studies to evaluate if (and which) blood-flow measurements might provide a noninvasive substitute for skin-biopsy tests. In Aim 2 these same patients will be offered ultrasound tests of heel-bone density to test the hypothesis that small-fiber polyneuropathies also cause bone loss. If this is true, such patients may have currently unappreciated risk for osteoporosis and bone fracture. Plus, modulating small-fiber effects on bone might offer potential new treatments for osteoporosis. Aim 3 involves collaboration with MGH's neuroradiologists to optimize 3-Tesla magnetic resonance imaging equipment and methods to permit physicians to see the chronic nerve injuries that leave some patients with "mystery pain" after seemingly minor or healed injuries.