Abstract
The most widely used model of Type I diabetic neuropathic pain (DNP) involves the injection of streptozotocin (STZ). Here we tested the hypothesis that behavioral signs of Type II DNP develop in the Zucker Diabetic Fatty (ZDF) rat. To do this, we evaluated behavioral responses to noxious mechanical (paw pressure), noxious heat (Hargreaves test and 52.5ºC hot‐plate test), and non‐noxious cool (6ºC cold plate) stimuli, blood glucose levels, in both ZDF obese rats and their lean controls. Rats arrived at 12 wk of age and were tested once a week for 12 weeks. Obese animals arrived hyperglycemic. Paw pressure threshold did not differ between strains at any time. Obese but not lean ZDF rats developed cold allodynia and heat allodynia at approximately 15 wk of age, and this was maintained for the duration of the study. Both cold and heat allodynia, but not hyperglycemia, were significantly reduced 105 min after a single intra‐peritoneal injection of the PPAR‐gamma agonist, pioglitazone in obese ZDF rats. These results suggest that the ZDF rat represents a more robust model of Type II DNP than previously thought, and indicate that FDA‐approved thiazolinedione drugs rapidly reduce DNP via a mechanism that is independent of their anti‐diabetic properties. Supported by NS62306, DA18732, and DA19656 to BKT.
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