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

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

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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.

Original languageEnglish
Article number4729284
JournalJournal of Diabetes
Publication statusPublished - 15 Feb 2017

Bibliographical note

This work was supported by a GlaxoSmithKline-BBSRC (UK) Ph.D. studentship (VLN; BB/J014478/1) and the authors thank the Centre for Integrated Mammalian Biology, Manchester, for support. Natalie J. Gardiner was supported by the Juvenile Diabetes Research Foundation (Natalie J. Gardiner: JDRF, USA: 2-2009-226). The authors thank Sumia Ali and Sarah Al-Adham for immunocytochemistry advice and Roger Meadows (University of Manchester Bioimaging Facility) for helping with microscopy.


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