Direct and indirect pharmacological modulation of CCL2/CCR2 pathway results in attenuation of neuropathic pain - In vivo and in vitro evidence

Anna Piotrowska; Klaudia Kwiatkowski; Ewelina Rojewska; Joanna Slusarczyk; Wioletta Makuch; Agnieszka Basta-Kaim; Barbara Przewlocka; Joanna Mika

doi:10.1016/j.jneuroim.2016.04.017

Direct and indirect pharmacological modulation of CCL2/CCR2 pathway results in attenuation of neuropathic pain - In vivo and in vitro evidence

J Neuroimmunol. 2016 Aug 15:297:9-19. doi: 10.1016/j.jneuroim.2016.04.017. Epub 2016 May 3.

Authors

Anna Piotrowska¹, Klaudia Kwiatkowski¹, Ewelina Rojewska¹, Joanna Slusarczyk², Wioletta Makuch¹, Agnieszka Basta-Kaim², Barbara Przewlocka¹, Joanna Mika³

Affiliations

¹ Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
² Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
³ Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: joamika@if-pan.krakow.pl.

PMID: 27397071
DOI: 10.1016/j.jneuroim.2016.04.017

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.

Keywords: CCL2/CCR2; Glia; Minocycline; Neuropathic pain; RS504393.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analgesics / therapeutic use*
Animals
Animals, Newborn
Benzodiazepines / therapeutic use
Benzoxazines / therapeutic use
Cells, Cultured
Chemokine CCL2 / genetics
Chemokine CCL2 / metabolism*
Chemokine CCL2 / therapeutic use
Disease Models, Animal
Gene Expression Regulation / drug effects
Hyperalgesia / drug therapy
Hyperalgesia / etiology
Male
Minocycline / pharmacology
Neuroglia / drug effects
Pain Threshold / drug effects
Physical Stimulation / adverse effects
Rats
Rats, Wistar
Receptors, CCR2 / genetics
Receptors, CCR2 / metabolism*
Sciatica / complications
Sciatica / drug therapy*
Signal Transduction / drug effects
Spinal Cord / drug effects
Spinal Cord / metabolism
Spiro Compounds / therapeutic use

Substances

Analgesics
Benzoxazines
Chemokine CCL2
RS 504393
Receptors, CCR2
Spiro Compounds
Benzodiazepines
SC 32855
Minocycline