Functional peripheral and central vagal neural circuits of interoception inhibiting pain

内感受抑制疼痛的功能性外周和中枢迷走神经回路

• 批准号: 10544768
• 负责人: Man-Kyo Chung
• 金额: $ 72.46万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10544768
• 关键词: Ablation; Absence of pain sensation; Address; Adult; Affective; Anxiety; Arthralgia; Attenuated; Brain; Brain region; Cell Nucleus; Cognitive; Data; Diphtheria Toxin; Dopamine; Dopamine Antagonists; Economic Burden; Electric Stimulation; Emotional; FDA approved; Fibromyalgia; Genetic; Genetic Recombination; Head and neck structure; Health; Homeostasis; Human; Image; Inflammation; Injections; Interoception; Mandible; Mastication; Mediating; Mental Depression; Migraine; Modeling; Mood Disorders; Motion; Mus; Muscle; Musculoskeletal structure; Myofascial Pain Syndromes; Nerve; Neurons; Nociception; Orofacial Pain; Outcome; Pain; Pain Management Method; Pathway interactions; Patients; Peripheral; Physiological; Population; Presynaptic Terminals; Prevalence; Process; Regulation; Reporting; Role; Seizures; Signal Transduction; Source; Spinal Cord; Structure of trigeminal ganglion; Temporomandibular Joint; Temporomandibular Joint Disorders; Temporomandibular joint disorder pain; Testing; Tissues; Trigeminal System; Vagus nerve structure; Work; chronic pain; chronic pain management; chronic painful condition; comorbidity; designer receptors exclusively activated by designer drugs; diphtheria toxin receptor; dopaminergic neuron; emotion regulation; experience; improved; in vivo; joint inflammation; mouse model; neural; neural circuit; neurobiological mechanism; neurochemistry; neuromechanism; novel; opioid epidemic; optogenetics; pain behavior; pain inhibition; pain processing; pain signal; parabrachial nucleus; psychosocial; sound; temporomandibular pain; transmission process; vagus nerve stimulation

Functional peripheral and central vagal neural circuits of interoception inhibiting pain Interoception is the sense of the physiological condition of the body, and is critical for maintaining homeostasis and regulating cognitive and emotional processes. The neural processing of interoception can be regulated by electrical stimulation of the vagus nerve, which led to an FDA-approved therapy for seizure and depression. Interestingly, vagal stimulation also modulates intractable chronic pain in patients. However, the road to improving chronic pain management through the regulation of interoceptive inputs is blocked by our ignorance of the neurobiological mechanisms whereby vagal activity modulates chronic pain, posing a significant hurdle. To overcome this hurdle, we will focus on the neural mechanisms of vagal modulation in a mouse model of inflammation in temporomandibular joint (TMJ), a surrogate model of temporomandibular disorders (TMD). TMD is a prevalent form of chronic pain that often occurs as a comorbidity with other chronic pain conditions, such as migraine and fibromyalgia. Since chronic pain involves a wide range of neural processes ranging from peripheral nociception to affective and cognitive processing in the brain, it is possible that interoceptive inputs regulate pain pathways through multiple peripheral and central mechanisms. Vagal stimulation was suggested to inhibit transmission of pain signals at spinal cord through the regulation of descending pain modulatory pathways. Considering the high comorbidity of chronic pain and affective disorders, such as anxiety or depression, vagal inputs likely modulate pain through regulation of brain regions involved in emotional regulation. Furthermore, pain is driven by nociceptive processing by pain-sensing nerves at peripheral tissues, but vagal regulation of nociception in the periphery has not been reported. Here, our objective is to determine functional neural mechanisms by which interoception inhibits pain. Our central hypothesis is that vagal interoceptive circuits intersect with peripheral and central nociceptive pathways to inhibit pain from TMJ. We will test this hypothesis in the following specific aims.

内感受抑制疼痛的功能性外周和中枢迷走神经回路 内感受是对身体生理状况的感觉，对于维持体内平衡至关重要 以及调节认知和情绪过程。内感受的神经处理可以通过以下方式调节 电刺激迷走神经，这导致了 FDA 批准的治疗癫痫和抑郁症的疗法。 有趣的是，迷走神经刺激还可以调节患者的顽固性慢性疼痛。然而，通往 我们的无知阻碍了通过调节内感受输入来改善慢性疼痛管理 迷走神经活动调节慢性疼痛的神经生物学机制的研究构成了一个重大障碍。 为了克服这个障碍，我们将重点研究小鼠模型中迷走神经调节的神经机制。 颞下颌关节（TMJ）炎症，颞下颌疾病（TMD）的替代模型。 TMD 是慢性疼痛的一种普遍形式，通常与其他慢性疼痛病症同时发生，例如 偏头痛和纤维肌痛。由于慢性疼痛涉及广泛的神经过程，从外周 伤害感受影响大脑中的情感和认知处理，内感受输入可能会调节疼痛 通过多种外周和中枢机制的途径。迷走神经刺激被认为可以抑制 通过调节下行疼痛调节通路来在脊髓传递疼痛信号。 考虑到慢性疼痛和情感障碍（例如焦虑或抑郁）的高合并症，迷走神经 输入可能通过调节涉及情绪调节的大脑区域来调节疼痛。此外， 疼痛是由周围组织的痛觉神经的伤害性处理驱动的，但迷走神经调节 尚未有周围伤害感受的报道。在这里，我们的目标是确定功能神经 内感受抑制疼痛的机制。我们的中心假设是迷走神经内感受回路 与外周和中枢伤害感受通路交叉，抑制颞下颌关节疼痛。我们将检验这个假设 在以下具体目标中。