The many different functions and brain regions associated with the vagus nerve have led researchers to test its usefulness in treating several illnesses, including epilepsy, treatment-resistant depression, anxiety disorders, Alzheimer’s disease, migraines, fibromyalgia, obesity, and tinnitus.
The Food and Drug Administration’s approval of a vagus nerve stimulator (VNS) subsequent to a 1997 neurological devices panel meeting has remained controversial. In the only randomized, controlled trial of severe depression, VNS failed to perform any better when turned on than in otherwise similarly implanted patients whose device was not turned on, according to the agency’s summary of the data.
However, the discovery in 2007 by Kevin J. Tracey that vagus nerve stimulation inhibits inflammation by suppressing pro-inflammatory cytokine production (inflammatory reflex) has led to significant interest in the potential to use this approach for treating inflammatory diseases ranging from arthritis to colitis, ischemia, myocardial infarction, and heart failure (J Clin Invest. 2007;117[2]:289-96).
At present, the study by Dr. Koopman and her colleagues showed that vagus nerve stimulation (up to four times daily) by the implantable VNS in rheumatoid arthritis (RA) patients significantly inhibited tumor necrosis factor (TNF) production for up to 84 days. RA disease severity apparently improved significantly. The results of this investigation seem to confirm the crucial role played by the neuroendocrine immune system network in RA (Nat Rev Rheumatol. 2011;7[9]:500-2).
However, the question now is: Are there issues and limitations about this possible new approach to RA treatment based on previous experiences? An obvious issue is the limited number of adverse events reported by the authors.
In contrast, adverse events have been signaled in all previous studies for VNS use as expected: cardiac arrhythmia during implantation, intermittent decrease in respiratory flow during sleep, posttreatment increase of apnea hypopnea index, and the development of posttreatment mild obstructive sleep apnea in up to one-third of patients, a minority of whom develop severe obstructive sleep apnea clearly related to VNS therapy. Another study has shown alteration of voice in 66%, coughing in 45%, pharyngitis in 35%, and throat pain in 28% (Pediatr Neurol. 2008;38[2]:99-103). Other reports of VNS device adverse events range from hoarseness (very common) to frank laryngeal muscle spasm and upper airway obstruction (rare). Other nonspecific symptoms include headache, nausea, vomiting, dyspepsia, dyspnea, and paresthesia.
At present, the approach of VNS therapy in RA needs further strict investigations, especially regarding the large number of potential adverse events expected. In addition, the target of reducing TNF levels in RA patients is already obtainable with several other noninvasive and established treatments.
Maurizio Cutolo, MD, is professor of rheumatology and internal medicine and director of the research laboratories and academic division of clinical rheumatology in the department of internal medicine at the University of Genova (Italy). He has no relevant disclosures.
