Neurostimulation of the Cholinergic Antiinflammatory Pathway in Rheumatoid Arthritis and Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) cause significant morbidity and mortality. Despite significant therapeutic advances, the medical need for patients with these disorders remains high. An important neural-immune regulatory mechanism termed the “inflammatory reflex,” and its efferent arm, the “cholinergic antiinflammatory pathway” regulate innate and adaptive immunity. An emerging body of evidence indicates that stimulation of this pathway with implantable medical devices is a feasible therapeutic approach in disorders of dysregulated inflammation. Herein we describe the underlying biology and the preclinical experiments done in standard animal models that provided the rationale for testing in clinical trials. The preclinical development approach comprised elements of classic drug and medical device development, yet had unique features and challenges. “Bioelectronic medicines” having ideal characteristics of both drugs and medical devices hold great conceptual promise for treatment of systemic diseases in the future. However studies being done today will help determine whether neurostimulation of the cholinergic antiinflammatory pathway (NCAP) has the potential in the nearer term to fulfill the needs of patients, caregivers and payers for an additional potential treatment option for inflammatory disorders, and might thus become one of the first feasible examples of a bioelectronic medicine.