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: 10372237
• 负责人: Mary Magdalen Heinricher
• 金额: $ 37万
• 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 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10372237
• 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; 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; chronic pain patient; chronic painful condition; clinical pain; extracellular; insight; migraine treatment; 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.

项目概要 许多慢性疼痛患者抱怨对多种感觉异常敏感 模态，包括光、声音和气味，潜在的神经基础仍然是一个谜。 这些说法常常受到怀疑，因为感觉敏锐度本身并不 初级感觉通路中的处理过程得到增强，也没有放大。 该提案的论点是，脑干疼痛调节系统的功能障碍已经 人们认为在这些情况下会导致疼痛，也可能在多感觉中发挥作用 这个假设是基于我们意外的观察，即一部分 延髓头端腹内侧的疼痛调节神经元，是重要神经元的最终输出 脑干疼痛调节系统，利用单细胞对光做出三个特定目标。 记录大鼠的方法，我们将充分表征 RVM 对光的响应，产生 我们还将确定刺激-反应函数并建立相关频谱。 在偏头痛动物模型中这些神经元的光反应性是否增强 头痛（光敏性已被充分记录）或处于持续炎症状态。 最后，我们将从更高的角度研究光响应性的“自上而下”调制 已知大脑结构会导致压力引起的痛觉过敏并与 目前的建议是对轻度压力的内分泌、自主神经和行为反应。 结合电生理学和行为学方法来确定光如何 参与疼痛调节系统，有效地将视觉刺激转化为躯体刺激 这些研究将提供基础的感觉，产生不适和厌恶。 深入了解多感觉超敏反应的神经生物学机制、信息 对于开发更合适的偏头痛和其他慢性疼痛治疗方法至关重要 失调。