Understanding multisensory hypersensitivity in chronic pain states

了解慢性疼痛状态下的多感觉超敏反应

• 批准号: 9332614
• 负责人: Mary Magdalen Heinricher
• 金额: $ 37.48万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-15 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9332614
• 关键词: Animal Model; Animals; Behavior; Behavioral; Brain; Brain Stem; Cells; Chronic; Clinical; Dependence; Electrophysiology (science); Elements; Endocrine; Equilibrium; Esthesia; Functional disorder; Hyperalgesia; Hypersensitivity; Hypothalamic structure; Inflammation; Inflammatory; Laboratories; Light; Mechanics; Migraine; Modality; Modeling; Neurons; Nociception; Output; Pain; Pain Disorder; Painless; Pathway interactions; Patients; Persistent pain; Phonophobias; Photophobia; Photosensitivity; Play; Rattus; Reporting; Response to stimulus physiology; Rodent Model; Role; Sensory; Smell Perception; Stimulus; Stress; Structure; System; Testing; Thalamic structure; Trigeminal System; Visual Pathways; Work; active control; base; behavioral response; chronic pain; extracellular; insight; multisensory; neurobiological mechanism; relating to nervous system; response; sound; transmission process; visual stimulus

PROJECT SUMMARY Many chronic pain patients complain of abnormal sensitivity to multiple sensory modalities, including light, sound, and smell. The underlying neural basis remains a puzzle and these claims are often viewed with suspicion, since sensory acuity per se is not enhanced, nor is there amplified processing in primary sensory pathways. The central thesis of this proposal is that dysfunction of brainstem pain-modulating systems, already thought to contribute to pain in these conditions, is also likely to play a role in multisensory hypersensitivity. This hypothesis is based on our unexpected observation that a subset of pain-modulating neurons in the rostral ventromedial medulla, the final output of an important brainstem pain-modulating system, respond to light. In three Specific Aims using single-cell recording approaches in rat, we will fully characterize the RVM response to light, generating stimulus-response functions and establishing the relevant spectrum. We will also determine whether photoresponsiveness of these neurons is enhanced in an animal model of migraine headache (where photosensitivity is well documented) or in a persistent inflammatory state. Finally, we will investigate “top-down” modulation of photoresponsiveness from a higher brain structure known to contribute to stress-induced hyperalgesia and implicated in endocrine, autonomic, and behavioral responses to mild stress. The present proposal brings together electrophysiological and behavioral approaches to determine how light engages pain-modulating systems, effectively converting a visual stimulus to a somatic sensation, producing discomfort and aversion. These studies will provide fundamental insights into the neurobiological mechanisms of multisensory hypersensitivity, information critical to developing more appropriate treatments for migraine and other chronic pain disorders.

项目摘要 许多慢性疼痛患者抱怨对多种含义的异常敏感性 方式，包括光，声音和气味。基础神经基础仍然是一个难题 而且这些主张通常会以可疑的方式看待，因为感觉敏锐本身不是 增强的，在主要感觉途径中也没有放大器处理。中央 该提议的论点是，脑干疼痛调节系统的功能障碍已经 被认为在这些条件下会导致疼痛的原因，也可能在多感官中发挥作用 高敏性。该假设是基于我们意外的观察结果，即 延髓腹侧髓质中的疼痛调节神经元，这是重要的最终输出 脑干调节系统，对光的反应。在三个特定目标中使用单细胞 大鼠记录方法，我们将充分表征RVM对光的响应，生成 刺激反应功能并建立相关频谱。我们还将确定 偏头痛动物模型中这些神经元的光呼应是否得到增强 头痛（光敏性有充分的记录）或处于持续的炎症状态。 最后，我们将调查从较高的较高的光报告调制的“自上而下”调制 大脑结构已知会导致压力引起的痛觉过敏，并与 内分泌，自主和行为对轻度压力的反应。目前的提议 汇集了电生理和行为方法，以确定如何光 参与疼痛调节系统，有效地将视觉刺激转化为体细胞 感觉，产生不适和厌恶。这些研究将提供基本 对多感觉超敏反应的神经生物学机制的见解，信息 对于为偏头痛和其他慢性疼痛开发更合适的治疗措施至关重要 疾病。