Potential anti-nociceptive role of chemokine CXCL1 in peripheral nerve injury-induced neuropathic pain

Abstract

Abstract Our previous studies have indicated that both microglial CD40 and spinal cord infiltrating CD4+ T cells play critical roles in the maintenance of peripheral nerve injury-induced neuropathic pain using a murine model of neuropathic pain, spinal nerve L5 transection (L5Tx). It is well accepted that chemokines play important role in the development of neuropathic pain. To further understand the role of microglial CD40 and CD4+ T cells in peripheral nerve injury-induced spinal cord chemokine response, we determined the levels of various chemokines in the lumbar spinal cord in CD40 knockout (KO), CD4 KO, and wild type (WT) BALB/c mice post-L5Tx. Using a multiplex assay, a total of eight chemokines CXCL1 (KC), CCL1 (TCA-3), CCL2 (MCP-1), CCL3 (MIP-1 alpha), CCL5 (RANTES), CCL11 (Eotaxin), CCL17 (TARC), and CCL22 (MDC) were examined. In WT mice, but not KO mice, L5Tx induced significant, gradual increases in CCL2, CCL3 and CCL5 up to day 21 post-L5Tx. At RNA level, L5Tx induced less pronounced increases of these chemokines in both types of KO mice compared to WT mice. These reduced chemokine response correlate with our previous observation that both CD40 KO and CD4 KO mice displayed significantly less mechanical hypersensitivity following L5Tx. Interestingly, L5Tx induced a significant increase in CXCL1 only in CD40 KO mice. Intrathecal injection of CXCL1 significantly reduced L5Tx-induced mechanical hypersensitivity in WT mice, indicating a potential protective effect of CXCL1 in neuropathic pain. Altogether, our data suggest chemokines’ roles in the development of neuropathic pain are chemokine type-specific.