CXCR4 chemokine receptor signaling mediates pain in diabetic neuropathy

Daniela M. Menichella*, Belmadani Abdelhak, Dongjun Ren, Andrew Shum, Caroline Frietag, Richard J. Miller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


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.

Original languageEnglish (US)
Article number42
JournalMolecular Pain
Issue number1
StatePublished - Jun 25 2014


  • Chemokine
  • DRG neurons
  • Neuropathic pain
  • Painful diabetic neuropathy

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Cellular and Molecular Neuroscience
  • Molecular Medicine


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