Contribution of CD137-CD137L pathway in sciatic nerve crush-induced behavioral hypersensitivity and functional reduction

Abstract

Abstract The T cell costimulatory molecule CD137L is involved in the development of neuropathic pain following peripheral nerve injury. Previously, our work has shown that absence or neutralization of CD137L reduces hypersensitivity, sensory and functional impairment following a sciatic nerve crush (SNC). CD137L activation utilizes both a CD137-dependent and a CD137-independent pathway. To further determine the contribution of these pathways, we examined pain-like and functional recovery-related behavioral responses following intrathecal injection (IT) of a CD137 neutralizing antibody (αCD137; daily days 3–10) after SNC in male and female B6 mice. Mice were randomly assigned to 1 of 4 groups: PBS, 0.5μg isotype control, 0.1 or 0.5μg of αCD137, and then were evaluated for sensitivity (von Frey, Hargreaves, & cold plantar test), sensory (pin prick assay) and motor (hind limb grip strength, toe spread reflex and toe spacing score) functions before surgery and on post-surgery days 1–77. On post-SNC day 1, all groups showed changes in sensitivity and decreased sensory and motor functions. αCD137 treatment did not alter mechanical, heat or hypersensitivity compared to PBS- or isotype-treated controls. αCD137-treated groups showed faster sensory (pin prick score) and motor functional recovery (toe spread reflex, toe spacing), as well as slightly greater improvement in grip strength test compared to controls. Together, our results indicate partial involvement of the CD137-dependent pathway in SNC-induced sensory and motor function changes following peripheral nerve injury. (Supported by NIH/NINDS R01NS098426 (Cao))