Astrocytic expression of CD137 in the lumbar spinal cord following sciatic nerve crush model of neuropathic pain in mice

Abstract

Previously we have shown that CD137–CD137 ligand (CD137L) mediates pro-nociceptive behaviors in the sciatic nerve crush (SNC) model of neuropathic pain. Global CD137L knockout (KO) mice and wildtype (WT) mice intrathecally treated with neutralizing antibody against either CD137L or CD137 displayed significantly reduced neuropathic pain-like behaviors and faster functional recovery compared to WT mice following SNC. To identify the cellular sources of CD137 and CD137L in the spinal cord, a series of immunohistochemistry analyses was performed. While we could not detect significant expression of CD137L (in part due to both technical and biological issues), we observed CD137 expression exclusively co-localized with astrocytic marker glial fibrillary acidic filament (GFAP). We then conducted a time course study of CD137 expression in the lumbar spinal cord dorsal horn region, the region relevant to nociceptive behaviors, in B6-CD137L KO and B6 WT mice. Significant increases in CD137 expression (represented by integrated density) were observed in WT mice from days 7 to 28 following either SNC or sham surgery. The expression of CD137 in KO mice was slightly (however not statistically significantly) higher than that in WT mice at baseline, and did not change overtime post-either surgery. When RNA expression of CD137 was evaluated, although SNC induced significant upregulation of GFAP RNA expression in WT mice, no changes in CD137 RNA expression were detected in any treatment groups or any genotype of mice. Altogether, we report a novel expression of CD137 on murine spinal cord astrocytes. The underlying mechanism through which astrocytic CD137 mediates SNC-induced nociceptive behavior requires further investigation. NIH/NINDS R01NS098426 (Cao) and Peter Caradonna from the COBRE Histology and Imaging Core funded by NIH/NIGMS P20GM103643 (Meng).