Boosting mind-body mechanisms for mitigating autonomic dysfunction in migraine

摘要 偏头痛(MIG)是一种流行的(15%-20%)高度致残性疾病，具有复杂的神经生物学特征 以自主神经失调为特征的基础。正念冥想(MM)已被提出为 一种可能改善自主神经功能的行为干预。我们自己的数据和其他人的数据发现 增强的副交感神经驱动力(高频心率变异性水平更高，或称HF- HRV)，在仅仅8周的冥想训练之后。此外，冥想训练还能改善情绪 杏仁核对应激源的调节和相应的激活减少，同样如图所示 通过我们自己的数据和其他人的数据。自主神经功能正常化与杏仁核缩小 对应激源的反应可能是偏头痛的一个重要治疗靶点。多模式方法具有 显示出改善的临床结果，并在最近的医学研究所报告中建议使用 疼痛。我们认为心身疗法也是如此。MM在治疗偏头痛方面表现出了希望，而且 可能通过自上而下的机制运作，潜在地降低杏仁核的反应性，同时增强 自主神经功能，外周(如用HF-HRV评估)和中枢(如用fMRI评估 中央自治网络，或称CAN)。 此外，自下而上的治疗方法，如侵入性和非侵入性耳廓经皮迷走神经 刺激(TVNS)还可以减少偏头痛的频率和致残率。迷走神经传入在迷走神经核内传递 延髓孤束可能调节三叉神经感觉复合体兴奋性和超兴奋性 在更高级的大脑结构中(即“自下而上”的路径)。此外，延髓背侧迷走神经系统 与呼吸同步工作：NTS接受延髓腹侧呼吸群的抑制性输入 (VRG)吸气时的核，呼气时的易化性输入。这是一个极其重要的特性 这个回路，因为它建议利用这个NTS途径的干预应该与 呼吸。因此，我们小组开发了呼吸门控的耳迷走传入神经刺激。 (RAVANS)，它通过仅在呼气相刺激来优化tVNS对NTS的靶向。因此， RAVANS TVNS结合了对皮质/皮质下超兴奋性的自下而上的调制。总而言之，我们建议 包括RAVANS TVNS的MM培训将在增强(中央和 外周)自主功能和减轻患者对应激源的杏仁核多动 偏头痛。

Abstract Migraine (MIG) is a prevalent (15-20%) and highly disabling disorder, with complex neurobiological underpinnings characterized by autonomic dysregulation. Mindfulness meditation (MM) has been proposed as a behavioral intervention that may improve autonomic functioning. Our own data, and those of others, found enhanced parasympathetic drive (as evidenced by higher levels of high-frequency heart rate variability, or HF- HRV), after only 8 weeks of meditation training. In addition, meditation training promotes improved emotion regulation and corresponding decreased activation of the amygdala in response to stressors, again as shown by our own data and those of others. Normalization of autonomic functioning and reduction of amygdala response to stressors may be an important therapeutic target in migraineurs. Multimodal approaches have shown improved clinical outcomes, and have been recommended in the recent Institute of Medicine report on pain. We propose that this is also the case for mind-body therapies. MM has shown promise for migraine, and likely operates by top-down mechanisms, potentially reducing amygdala reactivity as well as enhancing autonomic functioning, both peripherally (as assessed with HF-HRV) and centrally (as assessed with fMRI in the Central Autonomic Network, or CAN). Additionally, bottom-up therapies such as invasive and non-invasive auricular transcutaneous vagus nerve stimulation (tVNS) also reduce migraine frequency and disability. In tVNS, vagal afference relayed to nucleus tractus solitarii (NTS) in the medulla may modulate trigeminal sensory complex excitability and hyperexcitability in higher brain structures (i.e., a “bottom-up” pathway). Furthermore, the dorsal medullary vagal system operates in synchrony with respiration: NTS receiving inhibitory inputs from medullary ventral respiratory group (VRG) nuclei during inhalation, and facilitatory input during expiration. This is a critically-important feature of this circuitry, as it suggests that interventions utilizing this NTS pathway should be synchronized with respiration. Hence, our group developed Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS), which optimizes tVNS targeting of NTS by stimulating only during the expiratory phase. Thus, RAVANS tVNS incorporates bottom-up modulation of cortical/subcortical hyperexcitability. In sum, we propose that MM training incorporating RAVANS tVNS will have a synergistic effect in enhancing (both central and peripheral) autonomic functioning and in mitigating amygdalar hyperactivity in response to stressors in patients with migraine.