title: Central administration of C-X-C chemokine receptor type 4 antagonist alleviates the development and maintenance of peripheral neuropathic pain in mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anaesthesiology, The University of Hong Kong, HKSAR, China; Laboratory and Clinical Research Institute for Pain, The University of Hong Kong, HKSAR, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Anaesthesiology, The University of Hong Kong, HKSAR, China; Laboratory and Clinical Research Institute for Pain, The University of Hong Kong, HKSAR, China.
authors.forename: Wai Lydia
authors.initials: WL
authors.lastname: Tai
authors.affiliation: Department of Anaesthesiology, The University of Hong Kong, HKSAR, China; Laboratory and Clinical Research Institute for Pain, The University of Hong Kong, HKSAR, China.
authors.forename: Liting
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Anaesthesiology, The University of Hong Kong, HKSAR, China; Laboratory and Clinical Research Institute for Pain, The University of Hong Kong, HKSAR, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Department of Anaesthesiology, The University of Hong Kong, HKSAR, China; Research Center of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, HKSAR, China.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Anatomy, The University of Hong Kong, HKSAR, China; Research Center of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, HKSAR, China; Laboratory and Clinical Research Institute for Pain, The University of Hong Kong, HKSAR, China.
authors.forename: Sookja Kim
authors.initials: SK
authors.lastname: Chung
authors.affiliation: Department of Anaesthesiology, The University of Hong Kong, HKSAR, China; Research Center of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, HKSAR, China; Laboratory and Clinical Research Institute for Pain, The University of Hong Kong, HKSAR, China.
authors.forename: Chi Wai
authors.initials: CW
authors.lastname: Cheung
mesh_terms: D000818:Animals; D001596:Benzylamines; D015153:Blotting, Western; D000080027:Cyclams; D004305:Dose-Response Relationship, Drug; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D008026:Ligation; D051379:Mice; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D045442:Rotarod Performance Test; D012584:Sciatic Nerve / Q000601:surgery; D013116:Spinal Cord / Q000503:physiopathology
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor