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: 8056036
• 负责人: Anne Louise Oaklander
• 金额: $ 19万
• 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/8056036
• 关键词: Area; Award; Axon; Axotomy; Biopsy; Blood flow; Bone Density; Bortezomib; Caliber; Chronic; Clinical; Clinical Data; Clinical assessments; Collaborations; Complex Regional Pain Syndromes; Contralateral; Dana-Farber Cancer Institute; Data; Detection; Development Plans; Diabetes Mellitus; Diagnosis; Diagnostic; Diagnostic tests; Disease; Distal; Doctor of Medicine; Doctor of Philosophy; Dose; Electromyography; Environment; Equipment; Esthesia; Family; Fellowship; Fiber; Foundations; Fracture; Functional disorder; Funding; Funding Agency; General Hospitals; Goals; Healed; Healthcare Systems; Herpes zoster disease; Image; Injection of therapeutic agent; Injury; Interdisciplinary Study; Investigation; Joint Commission on Accreditation of Healthcare Organizations; Laboratory Diagnosis; Lasers; Left; Leg; Limb structure; Magnetic Resonance Imaging; Massachusetts; Measures; Methods; Minocycline; Minor; Modeling; Modification; Multiple Myeloma; National Institute of Neurological Disorders and Stroke; Nerve; Nerve Endings; Nerve Pain; Neural Conduction; Neuralgia; Neurites; Neurologic; Neurologist; Neurology; Neurons; Neuropathy; Nociception; Osteopenia; Osteoporosis; Pain; Pain Research; Patient Preferences; Patient Schedules; Patients; Peripheral Nerves; Pharmacologic Substance; Phase; Physicians; Polyneuropathy; Postdoctoral Fellow; Postherpetic neuralgia; Prevalence; Principal Investigator; Protocols documentation; Rattus; Recording of previous events; Research; Research Personnel; Resolution; Resources; Risk; Scanning; Sensory; Severities; Side; Skin; Skin Substitutes; Symptoms; Syndrome; Testing; Time; Tissues; Training; Ultrasonography; Velcade; Work; allodynia; axonal degeneration; blood flow measurement; bone; bone loss; calcaneum; care seeking; career; career development; chronic pain; density; diabetic; drinking water; effective therapy; healing; injured; loss of function; mechanical allodynia; medical schools; nerve injury; nerve supply; pain behavior; painful neuropathy; phase 2 study; prevent; sensory neuropathy; substantia spongiosa

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.

组织损伤引起的疼痛通常是短暂的，随着伤口的愈合，疼痛会消失。但一些患者有慢性疼痛，没有疾病或最近疼痛区域的损伤来解释它。这些“神秘的疼痛”患者在我们的医疗保健系统中的服务很差。他们中的许多人患有未被认识到的神经疾病或损伤，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。应聘者是医学博士、神经病学家和神经学家，在周围神经和疼痛方面有研究和临床研究员培训。她的长期职业目标是识别和研究神经病理性疼痛(神经痛)综合征，并开发更好的客观方法来诊断和研究它们。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，都与传递痛感和调节身体组织功能的小直径轴突(小纤维)的远端退化有关。小纤维损伤几乎不可能通过常规检查或测试(肌电/神经传导研究)来诊断，因此许多慢性疼痛患者仍处于无诊断或有效治疗的状态。这位候选人目前的职业目标是完成一项工作，表明因损伤而导致的局灶性神经痛患者身体另一侧的镜像神经以及直接受伤的神经存在轴突变性。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。哈佛医学院马萨诸塞州总医院(MGH)的环境提供了出色的资源、合作者和许多来自住院医生和研究员的潜在临床医生/研究人员培训人员。许多在MGH寻求治疗的慢性疼痛患者，包括那些被推荐到JCAHO认可的皮肤活检实验室诊断疑似小纤维多发性神经病的患者，为该项目提供了另一种资源。在MGH，这样的患者将小腿远端皮肤活检取出，并进行免疫标记，以便对其中的小纤维神经末梢进行计数。在AIM 1中，计划进行这种皮肤活组织检查的患者还将接受腿部远端、激光多普勒、皮肤血流研究，以评估是否(以及哪些)血流测量可以提供皮肤活组织检查的非侵入性替代。在目标2中，这些患者将接受脚跟骨密度的超声波测试，以验证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，这些患者目前可能有未被认识到的骨质疏松和骨折的风险。此外，调节小纤维对骨骼的影响可能会为骨质疏松症提供潜在的新疗法。AIM 3涉及与MGH的神经放射科医生合作，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，这些损伤使一些患者在看似轻微或痊愈的损伤后出现“神秘疼痛”。