PAIN AND PARESTHESIAS IN DIABETIC NEUROPATHY

糖尿病神经病的疼痛和感觉异常

• 批准号: 2272619
• 负责人: JOSE L OCHOA
• 金额: $ 21.29万
• 依托单位: GOOD SAMARITAN HOSP & MED CTR(PRTLND,OR)
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2272619
• 关键词: diabetic neuropathy; electrophysiology; human subject; hyperalgesia; inflammation; neural plasticity; neurophysiology; pain; pathologic process; sensory disorders; sensory mechanism

DESCRIPTION: In diabetes, the high prevalence, chronicity and crippling impact of sensory symptoms of neuropathic origin, such as parasthesias, spontaneous pains and hyperalgesias from skin and muscle, challenge the clinical scientist to update investigation of the pathophysiological bases of those anomalies. Basic scientific and clinical research have led, over the past decade, to discovery of abnormal peripheral and central neurophysiological mechanisms capable of inducing distressing sensations in neuropathy. There is also recent knowledge on processes which link sensory function with sympathetic nervous activity and also with sympathetic and nociceptor-mediated neurovascular control events. Such research has inspired the design of powerful new methods of investigation in humans: Among them are: *microneurography; intraneural microstimulation; measurement of biophysical factors that rectify nerve excitability; quantitate modality- specific psychophysical somatosensory tests; pharmacological and electrophysiologicaltests for sympathetic mediation of pain, and measurement of equivalents of neurogenic inflammation. Through applying a range of those methods we propose to investigate in patients with painful diabetic neuropathy the existence and mode of operation of newly recognized primary peripheral and secondary central abnormal sensory mechanisms which have been shown, by others and ourselves, to operate in neuropathic animals or in experimental human subjects. These include: *neurogenic inflammation and sensitization of pain receptors; abnormal biophysical rectification and ectopic electrical discharges in peripheral axons; central distribution of imbalanced afferent input; secondary breakdown and hyperexcitability of CNS circuits, and sympathetic mediation of sensory discharge. The contemporary medical paradigm on painful diabetic neuropathy is ready for a conceptual and methodological shift. The results anticipated from the present research plan would resteer current lines of investigation and management protocols for sensory dysfunction in diabetic neuropathy. Novel primary or secondary neuropathic mechanisms found to operate in general in diabetic neuropathy will be presented to scientists and to the industry as priorities for development of pharmacological or other treatment modalities. Individual patients will be spared therapies sometimes addressed at questionable mechanisms, and will be directed towards customized modalities of treatment.

描述：在糖尿病中，高患病率、慢性化和致残性 神经病理性起源的感觉症状的影响，如异感症， 来自皮肤和肌肉的自发性疼痛和痛敏，挑战 临床科学家将更新病理生理学研究 这些异常的基础。 在过去的十年里，基础科学和临床研究引领了 发现异常的外周和中枢神经生理学 能够在神经病中引起痛苦感觉的机制。 也有关于连接感觉功能的过程的最新知识 有交感神经活动，还有交感神经和 伤害性感受器介导的神经血管控制事件。这样的研究已经 启发了强大的人类研究新方法的设计： 其中包括： *显微神经摄影术；神经内微刺激；测量 纠正神经兴奋性的生物物理因素；量化形式- 特殊的心理物理体感试验.药理学和 交感神经调节疼痛的电生理测试，以及 神经源性炎症等效物的测量。 通过应用一系列这些方法，我们建议在 痛性糖尿病神经病变患者的存在及方式 新确认的初级外周和次级中枢的运作 异常的感觉机制，已经被其他人和 我们自己，在神经病动物或实验人类身上操作 研究对象。这些措施包括： *神经源性炎症和痛觉感受器敏化；异常 生物物理整流与外周异位放电 轴突；不平衡传入输入的中心分布；次级 中枢神经系统回路的击穿和过度兴奋，以及交感神经 感觉放电的调节。 痛性糖尿病神经病变的当代医学范式已经准备就绪 进行概念和方法上的转变。预期的结果来自 目前的研究计划将调整目前的调查方向 以及糖尿病神经病变感觉功能障碍的治疗方案。 新的原发或继发性神经病变机制在 糖尿病神经病变的一般情况将提交给科学家和 作为医药或其他行业优先发展的行业 治疗方式。个别患者将获得豁免治疗 有时是针对有问题的机制，并将针对 转向个性化的治疗方式。