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

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 b...

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Main Authors: Victoria L. Newton, Jonathan D. Guck, Mary A. Cotter, Norman E. Cameron, Natalie J. Gardiner
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2017/4729284
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author Victoria L. Newton
Jonathan D. Guck
Mary A. Cotter
Norman E. Cameron
Natalie J. Gardiner
author_facet Victoria L. Newton
Jonathan D. Guck
Mary A. Cotter
Norman E. Cameron
Natalie J. Gardiner
author_sort Victoria L. Newton
collection DOAJ
description 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.
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spelling doaj-art-abd3b6ff2733439fba29a7a32023e6082025-08-20T02:20:13ZengWileyJournal of Diabetes Research2314-67452314-67532017-01-01201710.1155/2017/47292844729284Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic NeuropathyVictoria L. Newton0Jonathan D. Guck1Mary A. Cotter2Norman E. Cameron3Natalie J. Gardiner4Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UKDivision of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UKSchool of Medical Sciences, University of Aberdeen, Aberdeen, UKSchool of Medical Sciences, University of Aberdeen, Aberdeen, UKDivision of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UKSpinal 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.http://dx.doi.org/10.1155/2017/4729284
spellingShingle Victoria L. Newton
Jonathan D. Guck
Mary A. Cotter
Norman E. Cameron
Natalie J. Gardiner
Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy
Journal of Diabetes Research
title Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy
title_full Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy
title_fullStr Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy
title_full_unstemmed Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy
title_short Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy
title_sort neutrophils infiltrate the spinal cord parenchyma of rats with experimental diabetic neuropathy
url http://dx.doi.org/10.1155/2017/4729284
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