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

- Minocycline decreased CCI-induced pain and upregulation of spinal CCL2 and CCR2.
- Minocycline reduced microglial upregulation of CCL2 and CCR2 after LPS stimulation.
- RS504393, CCR2 antagonist, reduced neuropathic pain in CCI-exposed rats.
- RS504393 decreased spinal microglial activation as well as CCL2 and CCR2.

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.

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