Differential lumbar spinal cord mononuclear cell responses among wild type, CD4 knockout, and CD40 knockout mice in spinal nerve L5 transection-induced neuropathic pain (54.17)

Abstract

Abstract We have previously demonstrated that both lumbar spinal cord-infiltrating CD4+ T cells and lumbar spinal cord microglial CD40 contribute to the maintenance of mechanical hypersensitivity in the murine model of neuropathic pain spinal nerve L5 transection (L5Tx). To further delineate the CD4 and CD40-mediated mechanisms involved in the development of L5Tx-induced neuropathic pain behaviors, we examined the lumbar spinal cord mononuclear cells of wild type (WT) BALB/c, BALB/c-CD4 knockout (KO), and BALB/c-CD40 KO mice in time course studies via flow cytometry. In WT mice, L5Tx significantly increased the total numbers of lumbar spinal cord mononuclear cells, microglial cells (CD45loCD11b+), and infiltrating leukocytes (CD45hi) in the ipsilateral side of the spinal cord on both days 3 and 7 post-surgery. Meanwhile, in CD4 KO mice, the only significant elevation in microglial cells was observed on day 7 post-L5Tx, and there were no increases in mononuclear cells and infiltrating leukocytes numbers post-L5Tx. On the other hand, in CD40 KO mice, L5Tx did not induce any of the changes observed in WT mice. Altogether, these data indicate that both CD4 and CD40 play a role in L5Tx-induced leukocyte infiltration into the lumbar spinal cord but have differential contributions to spinal cord microglial activation following peripheral nerve injury.