An early diagnostic tool for diabetic peripheral neuropathy in rats.

The skin's rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study was to investigate whether the skin rewarming rate in diabetic rats is related to microvascular changes and whether this is accompanied by changes observed in classical diagnostic methods for diabetic peripheral neuropathy. Computer-assisted infrared thermography was used to assess the rewarming rate after cold exposure on the plantar skin of STZ diabetic rats' hind paws. Peripheral neuropathy was determined by the density of intra-epidermal nerve fibers (IENFs), mechanical sensitivity, and electrophysiological recordings. Data were obtained in diabetic rats at four, six, and eight weeks after the induction of diabetes and in controls. Four weeks after the induction of diabetes, a delayed rewarming rate, decreased skin blood flow and decreased density of IENFs were observed. However, the mechanical hyposensitivity and decreased motor nerve conduction velocity (MNCV) developed 6 and 8 weeks after the induction of diabetes. Our study shows that the skin rewarming rate is related to microvascular changes in diabetic rats. Moreover, the skin rewarming rate is a non-invasive method that provides more information for an earlier diagnosis of peripheral neuropathy than the classical monofilament test and MNCV in STZ induced diabetic rats.

Long-term follow-up of peptidergic and nonpeptidergic reinnervation of the epidermis following sciatic nerve reconstruction in rats.

OBJECT: Peripheral nerve injuries are a commonly encountered clinical problem and often result in long-term functional deficits. The current gold standard for transected nerves is an end-to-end reconstruction, which results in the intermittent appearance of neuropathic pain. METHODS: To improve our understanding of the relation between this type of reconstruction and neuropathic pain, the authors transected and immediately end-to-end reconstructed the sciatic nerve in rats. The effect of this procedure on neuropathic pain, as measured by thermal and mechanical hypersensitivity at 4 different time points (5, 10, 20, and 30 weeks), was related to the density of peptidergic and nonpeptidergic fiber innervation in the glabrous skin of rats' hind paws. RESULTS: Thermal hypersensitivity occurring 20 weeks after reconstruction was accompanied by a significant increase in peptidergic epidermal fibers. However, the lesion-induced reduction in the density of nonpeptidergic epidermal fibers remained decreased at all experimental time points. Moreover, temporal collateral sprouting by undamaged saphenous nerve was visualized using the recently revised Evans blue extravasation technique. Strikingly, as the sciatic nerve repopulated rats' hind paw, the saphenous nerve withdrew to its original territory. CONCLUSIONS: The authors conclude that the transient thermal hypersensitivity is related to increased density of epidermal peptidergic fibers, which mainly originate from regenerating fibers. Furthermore, a changed composition in the peptidergic and nonpeptidergic epidermal fibers is demonstrated following end-to-end reconstruction of the sciatic nerve.