Model of acute painful diabetic neuropathy after rapid glycemic control
Acute painful diabetic neuropathy of rapid glycemic control (APDNRGC) is an acute and severe form of neuropathic pain, distinct from chronic neuropathic pain that afflict diabetic patients. APDNRGC develop after rapid glycemic control in both type 1 and type 2 diabetes. The pain may be sensitivity to temperature (thermal hyperalgesia) and/or touch (tactile allodynia), persists for months to years and rather resistant to conventional diabetic neuropathy treatment (Caravati, 1933, Tesfaye et al., 1996, Dabby et al., 2009, Gibbons and Freeman, 2010). The pathophysiology of APDNRGC is uncertain due to the lack of mechanistic knowledge resulting from the lack of animal models. This has precluded development of any therapy that could mitigate this debilitating condition. We have found that the insulin receptors are sensitized in diabetic rat sciatic nerve and that systemic insulin given to type 1 diabetic mice causes tactile allodynia within 60 min and persisted for at least 3 hours. In this proposal, we will develop and characterize a model of ADPNRGC for type 1 diabetes in order to understand the mechanism leading to this acute but persistent pain. We hypothesize that direct effects of insulin on peripheral nerve insulin receptors contribute to this condition. With this proposal, we aim at elucidating the pathogenic mechanisms for ADPNRGC, providing an avenue for effective therapies development.

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