Potential Benefit for Non Invasive Vagus Nerve Stimulation (nVNS) Using GammaCore in the Treatment of Raynaud's Phenomena.

Raynaud's phenomenon (RP) is a common vascular disorder that that affects approximately 10% of the general population. RP causes some areas of the body (i.e. fingers and toes) to feel cold and numb in response to cold exposure or emotional stress. Raynaud's phenomenon is characterized by reversible vasospasm of the fingers and toes. This reversible narrowing of the small arteries induces episodes of color changes of the fingers and toes. During an attack of Raynaud's, affected areas of the skin usually first turn white, then they often turn blue and feel cold and numb (pins and needles). As the fingers warm and circulation improves the affected areas may turn red, throb and tingle.

Moreover, Raynaud's phenomenon can be associated with significant morbidity that may include ulceration of fingers and loss of the fingers and toes due to repeated episodes of reversible narrowing of arteries supplying blood to the finger and toes. It is well known that cold exposure leads to episodes of RP, but the mechanism for cold sensitivity is not known, and treatment of RP is not satisfactory to the patients and their physicians.

Raynaud's phenomenon is classified as Primary Raynaud's phenomenon (PRP) in the absence of other vascular or connective tissue disease. Raynaud's phenomenon is classified as Secondary Raynaud's phenomenon (SRP) if it is associated with connective tissue disease, like systemic sclerosis (SSc, Scleroderma).

Treatment of Raynaud's phenomenon is not satisfactory in general, as current therapy employing calcium channel blockers and other vasodilators are frequently ineffective or not well tolerated, due to significant side effects.

Noninvasive vagus nerve stimulation (nVNS) is currently FDA approved for therapeutic uses in patient ages 12 and above to treat cluster and migraine headaches. Recent studies have shown that vagal nerve stimulation has vasodilatory and anti-inflammatory properties which has led to more preclinical research examining vagus nerve stimulation as treatment for a wider range of inflammatory and autoimmune disorders. Vagus nerve stimulation has shown promising results in treating chronic inflammatory disorders such as sepsis, lung injury, rheumatoid arthritis, and diabetes. Although there are no direct data to demonstrate vagus nerve stimulation's effect in Raynaud's phenomenon, the investigators believe that VNS's success in treating headache and migraine attacks indirectly support its use in Raynaud's phenomenon by its direct effect on vasospasms (narrowing of blood vessels). In fact migraine has been found as a risk factor for the development of Raynaud's phenomenon further supports this notion.