We will briefly introduce the topics to be covered in the session.

Brief overview of the FDA-cleared non-invasive neuromodulation devices for primary headaches.

Human imaging techniques such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and Magnetoencephalography (MEG) provide crucial insights to our understanding of central pain mechanisms.
This presentation will explore results from imaging data that elucidate the role of the descending pain modulatory system and its dysfunction in chronic pain as well as provide insights into brain activation and connectivity patterns involved in pain perception, pain modulation, and pain sensitization.
Additionally, brain imaging data that explore the neural processes and therapeutic effects underlying neurostimulation techniques for chronic pain will be discussed.

Vagus nerve antomy and physiology relevant to head pain will be reviewed. The clinical data for the use of non-invasive vagus nerve stimulation will be presented.

Descending circuits originating in multiple brain regions and signaling through the periaqueductal grey (PAG) and rostroventromedial medulla (RVM) to the dorsal horn of the spinal cord are critical in the endogenous modulation of pain. The output of these pathways uses multiple neurotransmitter systems to modulate incoming nociceptive signals as they enter the central nervous system and are projected to the brain. These circuits are influenced by opioids through mu-opioid receptors that are expressed throughout these pathways. Endogenous pain control under situations of extreme emotional states is also thought to be mediated by the activity of these circuits. This presentation will review the anatomy of these descending modulatory circuits. Also covered will be data from preclinical studies that have tested the physiology and pharmacology of pain modulatory circuits in rodent models. For example, preclinical studies have shown that activity of intact descending modulatory circuits can regulate the expression of pain through the release of norepinephrine in the spinal cord, which is consistent with the efficacy of drugs for pain that modulate norepinephrine release or reuptake (e.g. clonidine and nortriptyline). Data will also be presented from studies that have examined plasticity in these pathways that may contribute to persistent forms of pain.