Novel noninvasive approach to study the pathogenesis of chronic diabetic neuropathy

Abstract

Diabetic neuropathy is characterized by hyperalgesia, tactile allodynia andloss of sensation. Reduction in small fibres in the skin is observed in chronicdiabetic patients. In rats, short-term exposure to diabetes did not affect theepidermal nerve fibre density (ENFD) but increase in ENFD was observedafter longer exposure to diabetes, which is different from diabetic neuropathypatients. These discrepancy may rise from the invasive methods, whichinvolves many steps like skin biopsy and PGP9.5 staining. Here we made useof YFP transgenic mice that express high level of yellowish-green fluorescentprotein in motor and sensory neuronal cell bodies, axons and the terminals.They were induced to become diabetic by streptozotocin injection (200 mg/kg bw). In the anesthetized mice, the YFP positive epidermal nerve fibreswere quantitated under fluorescent stereo-microscope at different time pointof diabetes. There was no change in ENFD at 4 weeks and 8 weeks ofdiabetes, but there was reduction of ENFD at 22nd weeks. The delayed heatsensation response was observed in diabetic YFP mice at 4th, 8th, 22nd weekof diabetes. The present data showing no ENFD change at early stages ofdiabetes and reduction of ENFD at late stage of diabetes is consistent to theprevious report from the diabetic patients. This is the first novel noninvasivemethod to document the loss of epidermal nerve fibres and loss of sensationin chronic diabetic animal models. The YFP transgenic mouse model is aninvaluable tool for investigating the mechanism of the aetiology of diabeticneuropathy and determining therapeutic efficacy of experimental drugs inchronic diabetic animals.