Animal Models of Diabetic Neuropathic Pain

Pain is frequently the earliest and most problematic syndrome of distal peripheral neuropathy (DPN) in diabetic patients. The variety of time of onset, duration and progression, modalities, and severity of individual presentations of painful DPN makes classification and evaluation of mechanisms of pain in patients with diabetic neuropathy an outstandingly difficult task. One critical step to address this issue is the need for large-scale prospective studies that start in pain-free prediabetic or diabetic subjects and use questionnaires and neurological bedside and quantitative sensory tests standardized to assess progression of all possible modalities and types of pain. By their nature, however, even the best equipped and designed clinical studies remain mostly observational, and in-depth understanding of human disease is not possible without studies in animal models. Over the past several decades, a wide variety of rodent models of diabetes have been developed and characterized. Progression of DPN in many of these models has also been studied and confirmed, and in this work, we review those data with a specific focus on the utility, challenges, and limitations of using rodent models in research on mechanisms of diabetic pain.