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

基本信息

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
项目类别：
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

项目摘要

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.

互感的功能性周围和中央迷走神经回路抑制疼痛互感是身体生理状况的感觉，对于维持体内平衡至关重要并调节认知和情感过程。际观察的神经处理可以通过对迷走神经的电刺激，导致了FDA批准的癫痫发作和抑郁疗法。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。但是，通往我们的无知阻止了通过调节感知性输入来改善慢性疼痛管理神经生物学机制，迷走神经活性调节慢性疼痛，构成巨大的障碍。为了克服这一障碍，我们将重点介绍迷走神经调节的神经机制颞下颌关节（TMJ）的炎症，颞下颌疾病的替代模型（TMD）。 TMD 是一种慢性疼痛的一种普遍形式偏头痛和纤维肌痛。由于慢性疼痛涉及各种神经过程对大脑中情感和认知处理的伤害感，互感输入可能调节疼痛通过多个外围和中央机制的途径。建议迷走神经刺激抑制通过调节下降疼痛调节途径在脊髓处的疼痛信号传播。考虑到慢性疼痛和情感障碍的高合并症，例如焦虑或抑郁，迷走神经输入可能通过调节情绪调节的大脑区域来调节疼痛。此外，疼痛是由于周围组织的疼痛感应神经的伤害性处理而驱动的，但迷走神经调节尚未报道周围的伤害感。在这里，我们的目标是确定功能神经互认为抑制疼痛的机制。我们的中心假设是迷走神经感受性电路与周围和中央伤害感受途径相交以抑制TMJ疼痛。我们将检验这个假设在以下特定目标中。