Fibromyalgia Syndrome (FMS) is a chronic pain disorder of unknown origin, characterized by diffuse body pain and tenderness. Evidence is accumulating that the pathogenesis of FMS may be associated with central dysregulation of pain regulatory systems manifesting itself psychophysically in abnormally high pain sensitivity and intolerance thresholds. Based on physiological data derived from animals and psychophysical data derived from humans, VNS therapy was found to reduce the intensity of laboratory pain, especially when sensitization of the central pain regulatory system, known as wind-up, was induced. Wind-up is thought to underlie chronic pain in FMS. Thus, VNS therapy may be a viable adjunctive treatment option for FMS patients. Conventional drug and behavioral therapies have proven to be largely unsuccessful in relieving FMS pain over time. While opioid maintenance therapy, the current 'last resort' treatment option for FMS patients with severe, unrelenting pain, is efficacious, it is often avoided for fear of addiction. Thus, unrelieved FMS pain leads to poor quality of life, disability, economic disadvantage, and over utilization of the health care system. VNS has the potential to be a break-through non-pharmacological treatment modality to relieve FMS pain and halt this process. FMS patients who are disabled and depressed are usually considered to have the poorest prognosis. The proposed pilot study will be an open label, non-randomized single-arm, longitudinal, single-center study of VNS. We plan to implant and study 30 FMS patients representative of the spectrum of refractory FMS patients. All patients will have been treatment resistant to at least two levels of a conventional four level pharmacological FMS pain management protocol. In line with recent prevalence estimates, one-third of our selected FMS sample will be work disabled and two-thirds will not be. Likewise, one-third of FMS patients studied will not have a concurrent depressive disorder, while two-thirds will. The primary aim of this pilot study is to define the limits of VNS safety and tolerability in patients with refractory FMS. This study will provide data regarding the proportion of FMS patients tolerating implantation of the VNS device, activation, and ramp up of VNS output current, as well as stimulation over a 3-months, acute, and a 9 months follow-up study period. In addition, we will estimate the range of VNS output current tolerated and determine whether the rates of any adverse events are higher in FMS than epilepsy or depression samples. These data will inform the design of a Phase HI trial about maximal stimulation intensities and the minimum duration of a trial that is possible in these patients. The secondary aim of this study, assuming VNS is tolerated, is to assess the impact of VNS therapy on symptoms of FMS (including pain intensity, physical function, patient's global impression of change [FM20], mood, and quality of life, as well as laboratory measures of pain sensitivity). ? ?

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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Serrate-Sztein, Susana
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University of Medicine & Dentistry of NJ
Schools of Medicine
United States
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Lange, Gudrun; Janal, Malvin N; Maniker, Allen et al. (2011) Safety and efficacy of vagus nerve stimulation in fibromyalgia: a phase I/II proof of concept trial. Pain Med 12:1406-13