title: Direct and indirect pharmacological modulation of CCL2/CCR2 pathway results in attenuation of neuropathic pain - In vivo and in vitro evidence.
abstract: The repeated administration of microglial inhibitor (minocycline) and CCR2 antagonist (RS504393) attenuated the neuropathic pain symptoms in rats following chronic constriction injury of the sciatic nerve, which was associated with decreased spinal microglia activation and the protein level of CCL2 and CCR2. Furthermore, in microglia primary cell cultures minocycline downregulated both CCL2 and CCR2 protein levels after lipopolysaccharide-stimulation. Additionally, in astroglia primary cell cultures minocycline decreased the expression of CCL2, but not CCR2. Our results provide new evidence that modulation of CCL2/CCR2 pathway by microglial inhibitor as well as CCR2 antagonist is effective for neuropathic pain development in rats.
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Piotrowska
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Kwiatkowski
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Rojewska
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Slusarczyk
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Wioletta
authors.initials: W
authors.lastname: Makuch
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Basta-Kaim
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Przewlocka
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: joamika@if-pan.krakow.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Mika
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D001569:Benzodiazepines / Q000627:therapeutic use; D048588:Benzoxazines / Q000627:therapeutic use; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008911:Minocycline / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D012585:Sciatica / Q000150:complications / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013141:Spiro Compounds / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D048588:Benzoxazines; D018932:Chemokine CCL2; C579117:RS 504393; D054390:Receptors, CCR2; D013141:Spiro Compounds; D001569:Benzodiazepines; C035734:SC 32855; D008911:Minocycline
keywords: CCL2/CCR2; Glia; Minocycline; Neuropathic pain; RS504393