title: Role of monocyte chemoattractant protein-1, stromal derived factor-1 and retinoic acid in pathophysiology of neuropathic pain in rats.
abstract: BACKGROUND
  Chemokines have been recently recognized to play a role in chronic pain syndromes' pathophysiology. This study investigated the role of monocyte chemoattractant protein-1 (MCP-1), stromal cell derived factor-1 (SDF-1), and retinoic acid (RA) as targets for the therapeutic approach of neuropathic pain.
  
  
  METHODS
  A chronic constriction injury (CCI) model of neuropathic pain by unilateral ligation of left sciatic nerve was performed in adult female Wistar rats. The effects of doxycycline (Dox, 50 mg/kg/day i.p. for 7 days), single dose of bicyclam (5 mg/kg i.p.), RA (15 mg/kg/day i.p. for 7 days), and their combination(s) on behavioral tests of nociception (Von Frey filaments; paw pressure test) on days 0, 1, 3, 5, and 7 of operation were studied. Serum concentrations of MCP-1 and SDF-1 were measured by ELISA. Histological examination of the sciatic nerve was investigated.
  
  
  RESULTS
  CCI of sciatic nerve significantly induced mechanical allodynia and hyperalgesia and an increase of MCP-1 and SDF-1 serum levels. Dox-treated groups (Dox, Dox+bicyclam, Dox+RA, Dox+bicyclam+RA) and bicyclam-treated groups (bicyclam, Dox+bicyclam, bicyclam+RA, Dox+bicyclam+RA) attenuated CCI-induced behavioral and biochemical changes. RA inhibited CCI-induced mechanical hyperalgesia but produced a time-dependent reversal of allodynia. Histological findings showed degenerative changes of sciatic nerve after CCI that were partially recovered in Dox-treated groups.
  
  
  CONCLUSIONS
  These findings demonstrate an association between serum MCP-1 and SDF-1 concentrations and behavioral manifestations of neuropathic pain. RA administration decreased neuropathic pain (antihyperalgesic effect) but did not cause any improvement in sciatic nerve tissues, either alone or in combination with chemokine antagonists. Thus, chemokines may serve as potential targets for drug development in neuropathic pain treatment.
authors.forename: Enas Ahmed
authors.initials: EA
authors.lastname: Hamed
authors.forename: Hanan Sayed
authors.initials: HS
authors.lastname: Mohamed Farghaly
authors.forename: Asmaa Fathey
authors.initials: AF
authors.lastname: Abdel Mola
authors.forename: Minerva Kamal
authors.initials: MK
authors.lastname: Fahmi
authors.forename: Madiha Mohammed
authors.initials: MM
authors.lastname: Makhlouf
authors.forename: Mohamed Abdullah
authors.initials: MA
authors.lastname: Balfas
mesh_terms: D000818:Animals; D001596:Benzylamines; D018932:Chemokine CCL2 / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D000080027:Cyclams; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D009437:Neuralgia / Q000378:metabolism* / Q000473:pathology*; D059225:Nociception / Q000502:physiology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D001596:Benzylamines; C575935:CXCL12 protein, rat; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D014212:Tretinoin; D004318:Doxycycline; C088327:plerixafor