Pathophysiology and diagnosis of neurological pain syndromes

神经性疼痛综合征的病理生理学和诊断

• 批准号: 7472831
• 负责人: Anne Louise Oaklander
• 金额: $ 18.92万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7472831
• 关键词: Area; Axon; Biopsy; Blood flow; Bone Density; Caliber; Chronic; Clinical; Collaborations; Count; Development Plans; Diabetes Mellitus; Diagnosis; Disease; Distal; Doctor of Philosophy; Electromyography; Environment; Equipment; Esthesia; Fellowship; Fiber; Fracture; Functional disorder; General Hospitals; Goals; Healed; Healthcare Systems; Herpes zoster disease; Injury; Interdisciplinary Study; Laboratory Diagnosis; Lasers; Left; Leg; Magnetic Resonance Imaging; Massachusetts; Methods; Minor; Nerve; Nerve Endings; Neural Conduction; Neuralgia; Neurologic; Neurologist; Neurons; Nociception; Osteoporosis; Pain; Patient Schedules; Patients; Peripheral Nerves; Physicians; Polyneuropathy; Postherpetic neuralgia; Research; Research Personnel; Resources; Risk; Sensory; Side; Skin; Skin Substitutes; Syndrome; Testing; Tissues; Training; Ultrasonography; Work; blood flow measurement; bone; bone loss; calcaneum; care seeking; career; chronic pain; diabetic; healing; injured; loss of function; medical schools; nerve injury; nerve supply; painful neuropathy; sensory neuropathy

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.

描述（由申请人提供）：组织损伤引起的疼痛通常是短暂的，并随着损伤的愈合而消退。但有些患者有慢性疼痛，没有疾病或疼痛区域最近受伤来解释它。我们的医疗系统对这些“神秘疼痛”患者的服务很差。他们中的许多人患有未被发现的神经疾病或损伤，如果我们有更好的测试，这些疾病或损伤是可以被识别和治疗的。候选人是一名医学博士，神经学家和神经科学家，在周围神经和疼痛方面有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，并开发更好的客观诊断和研究方法。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）的远端变性有关。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没有得到诊断或有效的治疗。候选人的直接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的另一侧“镜像”神经以及直接受伤的神经中存在轴突变性。研究生涯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，麻省总医院（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/调查员实习生从住院医师和研究员。许多在MGH寻求治疗的慢性疼痛患者，包括那些被推荐到候选人jcaho认可的皮肤活检实验室诊断疑似小纤维多神经病变的患者，为该项目提供了另一种资源。在MGH，这样的患者需要切除一小块远端皮肤活检并进行免疫标记，以便计数其中的小纤维神经末梢。在Aim 1中，计划进行此类皮肤活检检查的患者还将提供远端腿部、激光多普勒、皮肤血流研究，以评估血流测量是否（以及哪种）可以作为皮肤活检检查的无创替代品。在目标2中，这些患者将接受足跟骨密度的超声检查，以验证小纤维多神经病变也会导致骨质流失的假设。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疗法。目标3包括与MGH的神经放射学家合作，优化3- tesla磁共振成像设备和方法，使医生能够看到慢性神经损伤，这些损伤使一些患者在看似轻微或愈合的损伤后留下“神秘的疼痛”。