Functional peripheral and central vagal neural circuits of interoception inhibiting pain

内感抑制痛的功能性外周和中枢迷走神经回路 内感是对身体生理状况的感觉，对维持体内平衡至关重要。 以及调节认知和情绪过程。内感的神经加工可以通过以下方式调节 电刺激迷走神经，导致FDA批准了一种治疗癫痫和抑郁症的方法。 有趣的是，迷走神经刺激也能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输入来改善慢性疼痛的治疗 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，我们将重点研究迷走神经调节的神经机制。 作为颞下颌关节紊乱病(TMD)的替代模型，TMJ中的炎症。TMD 是一种常见的慢性疼痛，通常与其他慢性疼痛状况共病，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，从外周到 伤害性感觉与大脑中的情感和认知过程有关，可能是内感输入调节疼痛。 通过多个外周和中枢机制的通路。迷走神经刺激被认为是抑制 通过调节下行痛觉调制通路在脊髓传递痛觉信号。 考虑到慢性疼痛和情感障碍的高共患率，如焦虑或抑郁、迷走 输入可能通过调节参与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进行的伤害性处理驱动的，但迷走神经对 外周的伤害性反应还没有报道。在这里，我们的目标是确定功能神经 内感抑制疼痛的机制。我们的中心假设是迷走神经内感觉神经回路 与外周和中枢伤害性通路交叉，以抑制来自TMJ的疼痛。我们将检验这一假设 在以下具体目标中。

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.