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: 8252176
• 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/8252176
• 关键词: Area; Axon; Biopsy; Blood flow; Bone Density; Caliber; Chronic; Clinical; Collaborations; 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; Joint Commission on Accreditation of Healthcare Organizations; 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; axonal degeneration; blood flow measurement; bone; bone loss; calcaneum; care seeking; career; career development; chronic pain; diabetic; effective therapy; healing; injured; loss of function; medical schools; nerve injury; nerve supply; painful neuropathy; sensory neuropathy; Area; Axon; Biopsy; Blood flow; Bone Density; Caliber; Chronic; Clinical; Collaborations; 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; Joint Commission on Accreditation of Healthcare Organizations; 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; axonal degeneration; blood flow measurement; bone; bone loss; calcaneum; care seeking; career; career development; chronic pain; diabetic; effective therapy; 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）：组织损伤导致的疼痛通常是短暂的，并且随着损伤的愈合而解决。但是一些患者患有慢性疼痛，没有疾病或最近的疼痛区域受伤来解释它。这些“神秘疼痛”患者受我们的医疗保健系统服务不佳。其中许多人患有不受欢迎的神经疾病或受伤，如果我们有更好的测试，可以被识别和治疗。该候选人是医学博士，博士神经科医生和神经科学家，负责周围神经和疼痛的研究和临床研究金培训。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，并开发出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引起的还是糖尿病等疾病，都与小直径轴突（小纤维）的远端变性有关，这些轴突（小纤维）传递疼痛感并调节身体的组织功能。通过常规检查或测试（肌电图/神经传导研究）几乎无法诊断小纤维损害，因此许多慢性疼痛患者在没有诊断或有效治疗的情况下仍处于困境。候选人的直接职业目标是完成工作，表明受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具有轴突变性。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。哈佛医学院的马萨诸塞州综合医院（MGH）环境，提供了来自居民和研究员中的许多潜在的资源，合作者以及许多潜在的临床医生/调查员学员。许多在MGH寻求护理的慢性痛苦患者，包括那些提到候选人的JCAHO认可的皮肤活检实验室来诊断可疑的小型纤维多神经病，为该项目提供了另一种资源。在MGH，此类患者的远端皮肤活检切除并进行了免疫标记，以允许计算其中的小纤维神经末端。在AIM 1中，计划进行此类皮肤活检测试的患者还将提供远端腿，激光多普勒，皮肤血液流量研究，以评估（以及哪个）血液 - 流量测量值是否可以提供皮肤生物检查测试的无创替代品。在AIM 2中，这些相同的患者将获得脚跟骨密度的超声测试，以测试小纤维多神经病也会导致骨质流失的假设。如果这是真的，此类患者目前可能目前可能会对骨质疏松症和骨折的风险产生批评。另外，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的神经放射学家合作，以优化3台磁共振成像设备和方法，以允许医生看到在看似轻微或愈合的伤害后，这些慢性神经损伤使一些“神秘疼痛”的患者造成了慢性神经损伤。