Noninvasive vagus nerve stimulation alters neural response and physiological autonomic tone to noxious thermal challenge

• Published in: PloS one 2019-02, Vol.14 (2), p.e0201212-e0201212
• Main Authors: Lerman, Imanuel, Davis, Bryan, Huang, Mingxiong, Huang, Charles, Sorkin, Linda, Proudfoot, James, Zhong, Edward, Kimball, Donald, Rao, Ramesh, Simon, Bruce, Spadoni, Andrea, Strigo, Irina, Baker, Dewleen G, Simmons, Alan N
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anesthesiology; Biology and Life Sciences; Brain; Brain - diagnostic imaging; Brain - physiopathology; Brain Mapping; Brain stem; Circuits; Computer engineering; Cortex (cingulate); Cortex (insular); Cortex (occipital); Cortex (somatosensory); Drug dosages; Epilepsy; FDA approval; Female; Functional magnetic resonance imaging; Galvanic skin response; Galvanic Skin Response - physiology; Headaches; Heart rate; Hot Temperature - adverse effects; Humans; Lower Extremity; Magnetic Resonance Imaging; Male; Medicine; Medicine and Health Sciences; Medulla oblongata; Mental depression; Mental health; Middle Aged; Motor nuclei; Nervous system; Neural circuitry; Neural networks; Neural Pathways - diagnostic imaging; Neural Pathways - physiopathology; Neural stimulation; Nuclei; Occipital lobe; Pain; Pain - diagnostic imaging; Pain - physiopathology; Pain Management - methods; Pain Perception - physiology; Physiological aspects; Physiology; Pilot Projects; Psychiatry; Research and Analysis Methods; Skin; Software; Somatosensory cortex; Stimulation; Stimuli; Thalamus; Thermal stimuli; Vagus nerve; Vagus Nerve Stimulation; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0201212

The mechanisms by which noninvasive vagal nerve stimulation (nVNS) affect central and peripheral neural circuits that subserve pain and autonomic physiology are not clear, and thus remain an area of intense investigation. Effects of nVNS vs sham stimulation on subject responses to five noxious thermal stimuli (applied to left lower extremity), were measured in 30 healthy subjects (n = 15 sham and n = 15 nVNS), with fMRI and physiological galvanic skin response (GSR). With repeated noxious thermal stimuli a group × time analysis showed a significantly (p < .001) decreased response with nVNS in bilateral primary and secondary somatosensory cortices (SI and SII), left dorsoposterior insular cortex, bilateral paracentral lobule, bilateral medial dorsal thalamus, right anterior cingulate cortex, and right orbitofrontal cortex. A group × time × GSR analysis showed a significantly decreased response in the nVNS group (p < .0005) bilaterally in SI, lower and mid medullary brainstem, and inferior occipital cortex. Finally, nVNS treatment showed decreased activity in pronociceptive brainstem nuclei (e.g. the reticular nucleus and rostral ventromedial medulla) and key autonomic integration nuclei (e.g. the rostroventrolateral medulla, nucleus ambiguous, and dorsal motor nucleus of the vagus nerve). In aggregate, noninvasive vagal nerve stimulation reduced the physiological response to noxious thermal stimuli and impacted neural circuits important for pain processing and autonomic output.