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Molecular Pain
Published in: Molecular Pain 1/2014

Open Access 01-12-2014 | Research

CXCR4 chemokine receptor signaling mediates pain in diabetic neuropathy

Authors: Daniela Maria Menichella, Belmadani Abdelhak, Dongjun Ren, Andrew Shum, Caroline Frietag, Richard J Miller

Published in: Molecular Pain | Issue 1/2014

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Abstract

Background

Painful Diabetic Neuropathy (PDN) is a debilitating syndrome present in a quarter of diabetic patients that has a substantial impact on their quality of life. Despite this significant prevalence and impact, current therapies for PDN are only partially effective. Moreover, the cellular mechanisms underlying PDN are not well understood. Neuropathic pain is caused by a variety of phenomena including sustained excitability in sensory neurons that reduces the pain threshold so that pain is produced in the absence of appropriate stimuli. Chemokine signaling has been implicated in the pathogenesis of neuropathic pain in a variety of animal models. We therefore tested the hypothesis that chemokine signaling mediates DRG neuronal hyperexcitability in association with PDN.

Results

We demonstrated that intraperitoneal administration of the specific CXCR4 antagonist AMD3100 reversed PDN in two animal models of type II diabetes. Furthermore DRG sensory neurons acutely isolated from diabetic mice displayed enhanced SDF-1 induced calcium responses. Moreover, we demonstrated that CXCR4 receptors are expressed by a subset of DRG sensory neurons. Finally, we observed numerous CXCR4 expressing inflammatory cells infiltrating into the DRG of diabetic mice.

Conclusions

These data suggest that CXCR4/SDF-1 signaling mediates enhanced calcium influx and excitability in DRG neurons responsible for PDN. Simultaneously, CXCR4/SDF-1 signaling may coordinate inflammation in diabetic DRG that could contribute to the development of pain in diabetes. Therefore, targeting CXCR4 chemokine receptors may represent a novel intervention for treating PDN.
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Metadata
Title
CXCR4 chemokine receptor signaling mediates pain in diabetic neuropathy
Authors
Daniela Maria Menichella
Belmadani Abdelhak
Dongjun Ren
Andrew Shum
Caroline Frietag
Richard J Miller
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Pain / Issue 1/2014
Electronic ISSN: 1744-8069
DOI
https://doi.org/10.1186/1744-8069-10-42

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