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

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很短暂，并随着损伤的愈合而消失。但有些患者患有慢性疼痛，但疼痛部位没有任何疾病或最近受伤。我们的医疗保健系统对这些“神秘疼痛”患者的服务很差。他们中的许多人患有未被意识到的神经疾病或损伤，如果我们有更好的测试，这些疾病或损伤是可以被识别和治疗的。该候选人是一位医学博士、博士神经学家和神经科学家，接受过周围神经和疼痛方面的研究和临床进修培训。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在没有诊断或有效治疗的情况下仍处于困境。该候选人的近期职业目标是完成一项工作，表明因受伤而患有局灶性神经痛的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。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、合作者以及来自住院医师和研究员的许多潜在的临床医生/研究人员培训生。许多在 MGH 寻求治疗的慢性疼痛患者，包括转诊至候选者 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个资源。在麻省总医院，此类患者会进行小腿远端皮肤活检并进行免疫标记，以便对其中的小纤维神经末梢进行计数。在 Aim 1 中，计划进行此类皮肤活检测试的患者还将接受远端腿部激光多普勒皮肤血流研究，以评估血流测量是否（以及哪些）可以提供皮肤活检测试的无创替代品。在目标 2 中，将对这些患者进行跟骨密度超声检查，以检验小纤维多发性神经病也会导致骨质流失的假设。如果这是真的，这些患者可能存在目前未被意识到的骨质疏松症和骨折风险。另外，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 涉及与 MGH 的神经放射科医生合作，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出现“神秘疼痛”。

项目成果

Neuropathic itch.

• DOI: 10.1016/j.sder.2011.04.006
• 发表时间: 2011-06
• 期刊: SEMINARS IN CUTANEOUS MEDICINE AND SURGERY
• 作者: Oaklander, Anne Louise

The complex regional pain syndrome.

• DOI: 10.1016/b978-0-444-62627-1.00026-3
• 发表时间: 2015-01-01
• 期刊: Handbook of clinical neurology
• 作者: Oaklander, Anne Louise;Horowitz, Steven H
• 通讯作者: Horowitz, Steven H

Response to "A new definition of neuropathic pain".

对“神经性疼痛的新定义”的回应。

• DOI: 10.1016/j.pain.2012.01.012
• 发表时间: 2012
• 期刊: Pain
• 影响因子: 7.4
• 作者: Oaklander,AnneLouise;Wilson,PeterR;Moskovitz,PeterA;Manning,DonaldC;Lubenow,Timothy;Levine,JonD;Harden,NormanR;Galer,BradleyS;Cooper,MarkS;Bruehl,Stephen;Broatch,James;Berde,Charles;Bennett,GaryJ
• 通讯作者: Bennett,GaryJ

Non-invasive Transcranial Magnetic Stimulation (TMS) of the Motor Cortex for Neuropathic Pain-At the Tipping Point?

• DOI: 10.5041/rmmj.10130
• 发表时间: 2013
• 期刊: Rambam Maimonides medical journal
• 影响因子: 1.5
• 作者: Treister R;Lang M;Klein MM;Oaklander AL
• 通讯作者: Oaklander AL

Experimental comparison of parametric versus nonparametric analyses of data from the cold pressor test.

冷压测试数据的参数与非参数分析的实验比较。

• DOI: 10.1016/j.jpain.2015.03.001
• 发表时间: 2015
• 期刊: The journal of pain
• 作者: Treister,Roi;Nielsen,ChristopherS;Stubhaug,Audun;Farrar,JohnT;Pud,Dorit;Sawilowsky,Shlomo;Oaklander,AnneLouise
• 通讯作者: Oaklander,AnneLouise