PMID- 26974138 OWN - NLM STAT- MEDLINE DCOM- 20170418 LR - 20211204 IS - 2191-0286 (Electronic) IS - 0792-6855 (Linking) VI - 27 IP - 4 DP - 2016 Jun 1 TI - Role of monocyte chemoattractant protein-1, stromal derived factor-1 and retinoic acid in pathophysiology of neuropathic pain in rats. PG - 411-24 LID - 10.1515/jbcpp-2015-0105 [doi] AB - 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. FAU - Hamed, Enas Ahmed AU - Hamed EA FAU - Mohamed Farghaly, Hanan Sayed AU - Mohamed Farghaly HS FAU - Abdel Mola, Asmaa Fathey AU - Abdel Mola AF FAU - Fahmi, Minerva Kamal AU - Fahmi MK FAU - Makhlouf, Madiha Mohammed AU - Makhlouf MM FAU - Balfas, Mohamed Abdullah AU - Balfas MA LA - eng PT - Journal Article PL - Germany TA - J Basic Clin Physiol Pharmacol JT - Journal of basic and clinical physiology and pharmacology JID - 9101750 RN - 0 (Benzylamines) RN - 0 (CXCL12 protein, rat) RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CXCL12) RN - 0 (Cyclams) RN - 0 (Heterocyclic Compounds) RN - 5688UTC01R (Tretinoin) RN - N12000U13O (Doxycycline) RN - S915P5499N (plerixafor) SB - IM MH - Animals MH - Benzylamines MH - Chemokine CCL2/*metabolism MH - Chemokine CXCL12/*metabolism MH - Cyclams MH - Disease Models, Animal MH - Doxycycline/pharmacology MH - Female MH - Heterocyclic Compounds/pharmacology MH - Hyperalgesia/drug therapy/metabolism MH - Neuralgia/*metabolism/*pathology MH - Nociception/physiology MH - Pain Measurement/methods MH - Pain Threshold/physiology MH - Rats MH - Rats, Wistar MH - Sciatic Nerve/metabolism MH - Tretinoin/*metabolism EDAT- 2016/03/15 06:00 MHDA- 2017/04/19 06:00 CRDT- 2016/03/15 06:00 PHST- 2015/08/29 00:00 [received] PHST- 2015/12/30 00:00 [accepted] PHST- 2016/03/15 06:00 [entrez] PHST- 2016/03/15 06:00 [pubmed] PHST- 2017/04/19 06:00 [medline] AID - /j/jbcpp.ahead-of-print/jbcpp-2015-0105/jbcpp-2015-0105.xml [pii] AID - 10.1515/jbcpp-2015-0105 [doi] PST - ppublish SO - J Basic Clin Physiol Pharmacol. 2016 Jun 1;27(4):411-24. doi: 10.1515/jbcpp-2015-0105.