Zucker Diabetic Fatty Rats as a Model for Painful Diabetic Neuropathy

Neuropathic pain is a severe complication of diabetic polyneuropathy (DPN). Preclinical evaluation of novel analgesics is mostly based on the rat Streptozotocin (STZ)-induced model that mimics features of diabetes type 1 and is typically characterized by an acute and severe development of the disease. However, there are currently no rodent models that reflect a more chronic phase of DPN. The current study evaluates evoked painlike and natural behaviors in twelve male Zucker Diabetic Fatty (ZDF) rat, a genetic model of spontaneously developed diabetes type 2, and twelve age-matched control Zucker Lean (ZL) rats over a period of in total 12 weeks. Withdrawal thresholds to tactile and pressure mechanical stimuli were significantly lower in ZDF rats compared to ZL rats staring with the onset of diabetes at the 9th week of age and persisted until the end of the study. In diabetic rats severity of mechanical allodynia was stably expressed, though mechanical hyperalgesia was constantly increasing throughout the study. Burrowing behavior and locomotor activity were significantly attenuated in diabetic rats compared to control rats. Both, reflex-withdrawal measures as well as the assessment of non-evoked, spontaneous behavior revealed a significant diabetes-associated behavioral alteration indicative of chronic pain. The research leading to these results is part of the Europain Collaboration, which has received support from the Innovative Medicines Initiative Joint Undertaking, under grant agreement no 115007, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007, 2013) and EFPIA companies' in kind contribution.