Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy.

Victoria L Newton,Mary A Cotter,Norman E Cameron,Natalie J Gardiner,Jonathan D Guck

doi:10.1155/2017/4729284

Abstract

Spinal glial cell activation and cytokine secretion have been implicated in the etiology of neuropathic pain in a number of experimental models, including diabetic neuropathy. In this study, streptozotocin- (STZ-) induced diabetic rats were either untreated or treated with gabapentin (50 mg/kg/day by gavage for 2 weeks, from 6 weeks after STZ). At 8 weeks after STZ, hypersensitivity was confirmed in the untreated diabetic rats as a reduced response threshold to touch, whilst mechanical thresholds in gabapentin-treated diabetic rats were no different from controls. Diabetes-associated thermal hypersensitivity was also ameliorated by gabapentin. We performed a cytokine profiling array in lumbar spinal cord samples from control and diabetic rats. This revealed an increase in L-selectin, an adhesion molecule important for neutrophil transmigration, in the spinal cord of diabetic rats but not diabetic rats treated with gabapentin. Furthermore, we found an increase in the number of neutrophils present in the parenchyma of the spinal cord, which was again ameliorated in gabapentin-treated diabetic rats. Therefore, we suggest that dysregulated spinal L-selectin and neutrophil infiltration into the spinal cord could contribute to the pathogenesis of painful diabetic neuropathy.

Highlights

The prevalence of diabetes mellitus is increasing worldwide, which has significant health and economic implications
We demonstrate an increase in the levels of L-selectin, an adhesion molecule important for neutrophil transmigration, in the lumbar spinal cord after 8 weeks of diabetes
These data suggest a role for dysregulated L-selectin and spinal vasculature in diabetes that leads to an increase in infiltrating neutrophils in experimental diabetic neuropathy, which is ameliorated by treatment with gabapentin

Summary

Introduction

The prevalence of diabetes mellitus is increasing worldwide, which has significant health and economic implications. Associated costs include both primary treatment and treating the associated secondary complications such as retinopathy, nephropathy, and neuropathy [1]. One of the first-line treatments is gabapentin [7], an analogue of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), an anticonvulsant drug which is antiallodynic in neuropathic and inflammatory pain states [8]. Gabapentin can interact with several targets, including the α2-δ subunit of voltage-activated calcium channels [9] and the L-amino acid transporters (LAT-1 and LAT-2; [10]) and has been shown to reduce spinal microglial activation and allodynia in rats with experimental diabetes [11, 12]

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