Central administration of C-X-C chemokine receptor type 4 antagonist alleviates the development and maintenance of peripheral neuropathic pain in mice

PLoS One. 2014 Aug 13;9(8):e104860. doi: 10.1371/journal.pone.0104860. eCollection 2014.

Abstract

Aim: To explore the roles of C-X-C chemokine receptor type 4 (CXCR4) in spinal processing of neuropathic pain at the central nervous system (CNS).

Methods: Peripheral neuropathic pain (PNP) induced by partial sciatic nerve ligation (pSNL) model was assessed in mice. Effects of a single intrathecal (central) administration of AMD3100 (intrathecal AMD3100), a CXCR4 antagonist, on pain behavior and pain-related spinal pathways and molecules in the L3-L5 spinal cord segment was studied compare to saline treatment.

Results: Rotarod test showed that intrathecal AMD3100 did not impair mice motor function. In pSNL-induced mice, intrathecal AMD3100 delayed the development of mechanical allodynia and reversed the established mechanical allodynia in a dose-dependent way. Moreover, intrathecal AMD3100 downregulated the activation of JNK1 and p38 pathways and the protein expression of p65 as assessed by western blotting. Real-time PCR test also demonstrated that substance P mRNA was decreased, while adrenomedullin and intercellular adhesion molecule mRNA was increased following AMD3100 treatment.

Conclusion: Our results suggest that central (spinal) CXCR4 is involved in the development and maintenance of PNP and the regulation of multiple spinal molecular events under pain condition, implicating that CXCR4 would potentially be a therapeutic target for chronic neuropathic pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Dose-Response Relationship, Drug
  • Heterocyclic Compounds / administration & dosage
  • Heterocyclic Compounds / pharmacology*
  • Injections, Spinal
  • Ligation
  • Mice
  • Neuralgia / drug therapy*
  • Neuralgia / etiology
  • Peripheral Nervous System Diseases / complications*
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Rotarod Performance Test
  • Sciatic Nerve / surgery
  • Spinal Cord / physiopathology

Substances

  • Heterocyclic Compounds
  • Receptors, CXCR4
  • plerixafor

Grant support

Funding for this study was provided by the departmental fund, Department of Anaesthesiology, The University of Hong Kong; the department fund, Department of Anaesthesiology, The University of Hong Kong had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.