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 内感受是对身体生理状态的感觉，对维持内环境稳定至关重要 以及调节认知和情绪过程。内感受的神经处理可以通过 迷走神经的电刺激，这导致了FDA批准的癫痫和抑郁症的治疗。 有趣的是，迷走神经刺激还调节患者的顽固性慢性疼痛。然而，通往 通过调节内感受性输入来改善慢性疼痛的管理被我们的无知所阻碍 迷走神经活动调节慢性疼痛的神经生物学机制，构成了一个重大障碍。 为了克服这一障碍，我们将集中在迷走神经调制的神经机制，在小鼠模型， 颞下颌关节（TMJ）炎症，颞下颌关节紊乱病（TMD）的替代模型。TMD 是一种常见的慢性疼痛形式，经常与其他慢性疼痛病症合并发生，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， 伤害性感受对大脑中的情感和认知过程的影响，内感受性输入可能调节疼痛 通过多种外周和中枢机制的通路。迷走神经刺激可抑制 疼痛信号在脊髓的传递通过下行疼痛调节通路的调节。 考虑到慢性疼痛和情感障碍（如焦虑或抑郁）的高共病率，迷走神经痛 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，委员会认为， 疼痛是由外周组织的痛觉神经的伤害性处理驱动的，但迷走神经对疼痛的调节是由外周组织的痛觉神经的伤害性处理驱动的。 尚未报道外周的伤害感受。在这里，我们的目标是确定功能性神经 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相交以抑制来自TMJ的疼痛。我们将检验这一假设 以下具体目标。

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.