Email updates

Keep up to date with the latest news and content from Molecular Pain and BioMed Central.

Open Access Highly Accessed Research

CXCR4 chemokine receptor signaling mediates pain in diabetic neuropathy

Daniela Maria Menichella1*, Belmadani Abdelhak2, Dongjun Ren2, Andrew Shum2, Caroline Frietag2 and Richard J Miller2

Author Affiliations

1 Department of Neurology, Robert Lurie Medical Research Center, Northwestern University, Lurie 8-123, 303 E. Superior St, Chicago, IL, USA

2 Department of Molecular Pharmacology, Northwestern University, Chicago, IL, USA

For all author emails, please log on.

Molecular Pain 2014, 10:42  doi:10.1186/1744-8069-10-42

Published: 25 June 2014

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.

Keywords:
Chemokine; Neuropathic pain; Painful diabetic neuropathy; DRG neurons