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Neuroscience. 2018 Feb 21;372:225-236. doi: 10.1016/j.neuroscience.2017.12.048. Epub 2018 Jan 6.

Anti-nociceptive Role of CXCL1 in a Murine Model of Peripheral Nerve Injury-induced Neuropathic Pain.

Author information

1
Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA; Center for Excellence in the Neurosciences, University of New England, Biddeford, ME 04005, USA; Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04473, USA. Electronic address: lcao@une.edu.
2
Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA; Center for Excellence in the Neurosciences, University of New England, Biddeford, ME 04005, USA.

Abstract

Both spinal cord infiltrating CD4+ T lymphocytes and microglial CD40 contribute to the maintenance of neuropathic pain-like behaviors induced by spinal nerve L5 transection (L5Tx), a murine model of neuropathic pain. Here, we sought to investigate the involvement of multiple chemokines in microglial CD40-mediated and CD4+ T lymphocytes-mediated L5Tx-induced sensory hypersensitivity. Spinal cord chemokine expression in CD4 knockout (KO), CD40 KO, and wild type (WT) BALB/c mice was determined at the protein level via multiplex assays and at the RNA level via quantitative real-time PCR. In WT mice, L5Tx induced significant increases in CCL2, CCL3, and CCL5 expression (protein and RNA) up to day 21 post-L5Tx, while CD4 KO mice displayed blunted, predominantly non-significant, responses in these chemokines at protein levels post-L5Tx. L5Tx also induced increased expression of these chemokines in CD40 KO mice; however, the overall protein levels of these chemokines were significantly lower than those in WT mice. Further, L5Tx induced a significant increase in CXCL1 at the protein level and in CXCR2 at RNA level only in CD40 KO mice. Intrathecal administration of CXCL1 in WT mice significantly reduced L5Tx-induced mechanical hypersensitivity. CD40 KO mice also displayed higher levels of Ly6G (neutrophil marker) RNA expression in the lumbar spinal cord post-L5Tx. Altogether, our data suggest that CD4+ T lymphocytes and microglial CD40 mediate their pro-nociceptive effects in part by promoting selected chemokine responses, and more importantly, CXCL1 can play an anti-nociceptive role in peripheral nerve injury-induced neuropathic pain, which is possibly mediated by infiltrating neutrophils.

KEYWORDS:

CD4; CD40; CXCL1; chemokines; neuropathic pain; spinal nerve L5 transection

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