Role of CD137L in lumbar spinal cord microglial responses following sciatic nerve crush

Abstract

Abstract Neuropathic pain is one of the most devastating kinds of chronic pain, which is still largely treated sub-optimally in part due to incomplete understanding. Using murine sciatic nerve crush (SNC) model, we have shown that spinal cord CD137 ligand (CD137L; AKA 4-1BBL) contributes to the development of SNC-induced pain-like behaviors and functional recovery following SNC. Here, we further investigated the potential involvement of lumbar spinal cord microglial responses in CD137L-mediated behavioral changes following SNC. Mononuclear cells were isolated from lumbar spinal cords of both wild type (WT) B6 and B6_CD137L knockout (KO) mice via Percoll gradient followed by flow cytometric analysis at days 0 (naïve), 3, 7, 14, 28 and 56 following SNC or sham surgery. Microglia were identified as CD45lowCD11b+ populations. In WT mice, the total number of microglia peaked at day 14 and then gradually reduced following SNC. The increase of microglial numbers was minimal in all other groups compared to the WT SNC mice. Similar pattern of changes were also observed with the numbers of CD86+ microglia (pro-inflammatory phenotype) and CD206+ microglia (anti-inflammatory phenotype), however the numbers of CD206+ microglia were much less. Our results support the notion that reduced lumbar spinal cord microglial responses contributes to the reduction of pain-like behaviors and improved functional recovery in CD137L deficient mice. CD137L-mediated microglial responses will be further investigated to elucidate the role of spinal cord CD137L in the development of neuropathic pain. (Supported by NIH/NINDS R01NS098426 (Cao))