Absence of CD137L decreases mechanical hypersensitivity and functional recovery time following sciatic nerve crush

Abstract

Abstract CD137 Ligand (CD137L), a tumor necrosis factor superfamily molecule, is involved in immune responses such as migration, proliferation and production of cytokines. To investigate the involvement of CD137L in pain development and nerve regeneration following peripheral nerve injury, we examined various pain-like and functional recovery-related behavioral responses in CD137L knockout (KO) mice and wild type (WT) B6 mice following sciatic nerve crush (SNC). Male and female B6 WT and CD137LKO mice underwent a sham or SNC surgery and were evaluated for hypersensitivity (von Frey, Hargreaves & cold water tail withdrawal tests), sensory (pin prick assay) and motor (hind limb grip strength, toe spread reflex and toe spacing score) functional recovery. Behaviors were assessed before surgery and on post-surgery days 1–77. On post-SNC Day 1, both KO and WT mice showed increased hypersensitivity and decreased sensory and functional responses. By Day 7, CD137LKO mice showed reduced mechanical hypersensitivity compared to WT and were responding at sham levels by Day 42, whereas WT controls reached sham levels by Days 56–63. Lack of CD137L did not alter warm or cold thermal hypersensitivity. Grip strength improved in both strains beginning on Day 7, but CD137LKO mice reached sham levels faster than WT controls (Day 17 vs. Day 70). No differences were found on toe spread reflex and toe spacing scores. Finally, pin prick scores revealed that sensory recovery in both strains of mice emerged on Day 7, but the CD137LKO mice responded similar to shams by Day 28, one week earlier than WT. Together, these results suggest that CD137L mediates the sensory hypersensitivity and impedes the restoration of sensory and motor functions following peripheral nerve injury.