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

doi:10.1155/2017/4729284

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

Medical Sciences

University of Manchester

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

9 Downloads (Pure)

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.

Original language	English
Article number	4729284
Journal	Journal of Diabetes
Volume	2017
DOIs	https://doi.org/10.1155/2017/4729284
Publication status	Published - 15 Feb 2017

Bibliographical note

Acknowledgments
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.

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1155/2017/4729284Licence: CC BY

Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy
Copyright © 2017 Victoria L. Newton et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/
Final published version, 3.86 MBLicence: CC BY

Cite this

@article{8f4df490a72b4e21a5744ef241903d1d,

title = "Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy",

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.",

keywords = "Journal Article",

author = "Newton, {Victoria L} and Guck, {Jonathan D} and Cotter, {Mary A} and Cameron, {Norman E} and Gardiner, {Natalie J}",

note = "Acknowledgments 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.",

year = "2017",

month = feb,

day = "15",

doi = "10.1155/2017/4729284",

language = "English",

volume = "2017",

journal = "Journal of Diabetes",

issn = "1753-0393",

publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy

AU - Newton, Victoria L

AU - Guck, Jonathan D

AU - Cotter, Mary A

AU - Cameron, Norman E

AU - Gardiner, Natalie J

N1 - Acknowledgments 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.

PY - 2017/2/15

Y1 - 2017/2/15

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1155/2017/4729284

DO - 10.1155/2017/4729284

M3 - Article

C2 - 28293643

SN - 1753-0393

VL - 2017

JO - Journal of Diabetes

JF - Journal of Diabetes

M1 - 4729284

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this