An early diagnostic tool for diabetic peripheral neuropathy in rats.

Shoista Kambiz,Marit H N Van Velzen,Steven E R Hovius,Joop A M J L Janssen,Naim Avazverdi,Saniye G Cosgun,Johan W Van Neck,Erik T Walbeehm

doi:10.1371/journal.pone.0126892

Abstract

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.

Highlights

Diabetic peripheral neuropathy is a common complication of diabetes
Diabetes was diagnosed in rats, when blood glucose levels were higher than 20 mmol/L during the entire 4 weeks after the induction of diabetes
While the blood flow remained low during further follow-up at 6 and 8 weeks after induction of diabetes, no significant difference in the percentage of CD31-positive endothelial cells was seen between diabetic rats and controls at these time points (Fig 4b–4f)

Summary

Introduction

Diabetic peripheral neuropathy is a common complication of diabetes. Assessment of the density of IENFs in a skin biopsy is considered to be a reliable method to measure diabetic peripheral neuropathy in both human diabetes and animal models with diabetes [1, 2]. Taking skin biopsies may be considered a risk factor in a disease where wound healing is prone to be disturbed. Skin biopsies cover only a small area and are invasive. Corneal nerve parameters and nerve conduction velocity are non-invasive diagnostic tools to determine.

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