Involvement of CD137L in peripheral nerve injury-induced neuropathic pain behaviors (CAM1P.161)

Abstract

Abstract CD137L, also known as 4-1BBL, is a co-stimulatory molecule involved in many immune functions. CD137L-mediated signaling can promote monocyte/macrophage proliferation, migration, and production of proinflammatory factors; however, CD137L-mediated microglial responses have not been studied extensively. Here, we sought to investigate the role of microglial CD137L in the development of peripheral nerve injury-induced neuropathic pain using a murine model, spinal nerve L5 transection (L5Tx). First, compared to wild type (WT) controls, B6_CD137L knockout (KO) mice displayed significantly decreased L5Tx-induced mechanical and heat hypersensitivity starting at day 3 post-L5Tx until day 35 post-L5Tx when the experiment was terminated. To further determine the role of microglial CD137L, an anti-CD137L neutralizing antibody (Ab, clone TKS-1) was intrathecally injected into WT BALB/c mice daily from day 0 (before surgery) to day 7 post-L5Tx. The neutralizing Ab significantly reduced L5Tx-induced mechanical hypersensitivity but not the heat hypersensitivity. Our data indicate that spinal cord CD137L contributes to the maintenance of peripheral nerve injury-induced neuropathic pain-like behaviors. Future study will examine the involvement of microglial CD137L in L5Tx-induced lumbar spinal cord microglial and astrocyte activation.