Small fiber neuropathy is a disease in which the nerves that transmit painful signals from the body to the brain are dysfunctional. Patients with this disease suffer debilitating symptoms, most notably pain that feels like burning, shocking or stabbing. Emerging evidence increasingly points toward dysfunction of the immune system as a cause of some cases of small fiber neuropathy. In particular, recent work has identified autoantibodies to the Fibroblast Growth Factor Receptor 3 (FGFR3) in some patients with small fiber neuropathy. However, it is unknown whether these autoantibodies are the actual cause of small fiber neuropathy in these patients, or whether another pathological process is at work. Thus, the major goal of this project is to determine whether autoantibodies against FGFR3 do indeed cause small fiber neuropathy. To answer this question, we will use a translational strategy in which we evaluate the ability of patient-derived FGFR3 autoantibodies to produce features of small fiber neuropathy both in vivo and in vitro. The findings of this project will provide much needed insight into the role of FGFR3 autoantibodies in small fiber neuropathy and will provide a critical foundation for the development of novel therapies for this debilitating disease.