This will be a two-stage study to test whether t-VNS using the NEMOS device can activate the CAP and reduce markers of systemic inflammation. Stage A (healthy volunteers) stage B (patients with Juvenile Idiopathic Arthritis).

Stage A: healthy human volunteers. A randomized, single blind, three-period crossover design comparing the CAP activation effect of 10 minutes (active) versus 60 minutes (active) versus 10 minutes (sham) stimulation with the NEMOS device. CAP activation will be assessed by reduction in the in vitro release of LPS-inducible cytokines from whole blood.

Analysis of the reduction in whole blood cytokine release assay after 10 versus 60 minutes of stimulation, and the kinetics of the nadir of the whole blood cytokine release assay will inform the selection of dose duration and sampling time for Stage B. Performing this more extensive exploration of dose duration and kinetics in adults will allow one dose, and a single optimal sampling time in the JIA patients, thus minimizing blood drawing and discomfort in these children.

Stage B will be performed in patients with JIA. This will be an open label design examining the effect of the optimal dose duration (either 10 minutes or 60 minutes of stimulation, as determined by results of Stage A). All information regarding Stage B will be registered in a separate registration at clincialtrials.gov. in order to keep accuracy. All details below concerns only Stage A.

The vagus nerve mediates the "inflammatory reflex"; a mechanism the central nervous system utilizes to regulate innate and adaptive immunity (Andersson, 2012). The afferent arm of the reflex senses inflammation both peripherally and in the central nervous system, and down-regulates the inflammation via efferent neural outflow. The efferent arm of this reflex has been termed the "cholinergic anti-inflammatory pathway" (CAP). The reflex serves as a physiological regulator of inflammation by responding to environmental injury and pathogens with an appropriate degree of immune system activation An increasing body of evidence indicates that the CAP can also be harnessed to reduce pathological inflammation. Electrical neurostimulation of the vagus nerve (VNS) with either a surgically implantable device, or alternatively using a non-invasive device that stimulates the auricular branch of the vagus nerve (ABVN) may be a feasible means of modulating diseases characterized by excessive and dysregulated inflammation.

Inclusion Criteria:

• Signed informed consent
• Males and females ages 18-75, inclusive
• Subjects must be free from any active disease, and must not be on any medication that, in the opinion of the investigator, might compromise the measurement or interpretation of the study biomarkers
• Subjects must be able to attend all study visits

Exclusion criteria:

• Significant psychiatric disease or substance abuse
• Anatomic abnormalities, wounds, significant scars or skin disorders affecting the left pinna or external ear canal which would hinder the safe and proper use of the study device
• History of unilateral or bilateral vagotomy
• History of recurrent vasovagal syncope episodes
• Women who are pregnant or plan to conceive during the study. Women of childbearing potential must be willing to use a reliable form of birth control during the study.
• Known history of cardiac rhythm disturbances, atrioventricular block of greater than first degree, or cardiac conduction pathway abnormalities other than isolated right bundle branch block or isolated left anterior fascicle block
• Presence of previously implanted electrically active medical devices (e.g., cardiac pacemakers, automatic implantable cardioverter-defibrillators), or plans to implant such devices during the course of the study
• Planned use of any other external electrically active medical device during the course of the study (e.g., transcutaneous electrical nerve stimulation [TENS] units)
• Any investigational small molecule drug within 30 days of Day 0, visit investigational monoclonal antibody or soluble receptor within 3 months of Day 0 visit