Gulf War Illness (GWI) has been a recognized consequence of our fighting the first Gulf War since spring of 1991 and still no treatments specifically for it exist. During the years since the first Gulf War, pharmaceutical treatments have become available for one complaint of Gulf Veterans with GWI, namely widespread pain and achiness. However, these treatments have three major drawbacks: they don't work on all patients; their effect often does not last more than a few months; and the side effects they produce are often so bad as to preclude their use. We present here a plan to test a new treatment to improve the widespread pain reported by many Gulf Veterans -- a hand-held device that stimulates the vagus nerve in the neck.

Vagus nerve stimulation (VNS) is approved by the Food and Drug Administration (FDA) to treat treatment-resistant epilepsy and depression. We became interested in using VNS as a modality to treat widespread pain for two reasons: first, patients receiving VNS reported having less pain and second, drugs to treat epilepsy and depression are in the same class as newly approved drugs to treat the widespread pain characteristic of fibromyalgia, a diagnosis which many Gulf vets also have. We did a safety and tolerability study in 14 women with fibromyalgia who tolerated surgical implantation and activation of the device as well as patients with the other FDA-approved indications for its use. Strikingly, many of the women got so much better that they no longer fulfilled criteria for the diagnosis of fibromyalgia. To determine that this effect was specific to VNS and was not a non-specific "placebo" type of response, a follow-up study comparing the actual device to one designed not to stimulate the vagus nerve is necessary.

We propose doing such a study on Gulf Veterans with GWI, characterized by a problem with widespread pain. Besides their pain, we will also assess the effect of VNS in alleviating migraine headache, another complaint of Gulf Veterans, which is common in the presence of widespread pain. Importantly, we are partnering with a company that has made a hand-held device that allows for stimulation of the vagus nerve without the need for surgery; it works by the patient putting it on the skin overlying the vagus nerve in their neck and then turning it on for 90-second periods three times a day. The device is programmed to deliver only six bouts of stimulation per day -- one to each side of the neck three times a day. It is then inactive until the next day. The fact that this device can be used without surgery and is non-invasive makes it extremely practical for use.

After collecting pretreatment measurement of pain severity and headache severity, Veterans will receive either the actual active VNS device or an inactive device, which does not stimulate the nerve. Veterans will use their device for 10 weeks -- providing similar information periodically over this period by responding to questions about the severity of their pain and headaches. They will then return to the Center for the final phase of the study where all Veterans will receive active devices. Ten weeks later, they will return to the Center to provide information to allow the investigators to gain further knowledge as to the effectiveness of actual VNS in relieving pain -- both throughout the body and in the head.