Early treatment of a CD137L neutralizing antibody decreases mechanical hypersensitivity and functional recovery time following a sciatic nerve crush

Abstract

Abstract To investigate the role of CD137L in pain development and nerve regeneration following peripheral nerve injury, we examined pain-like and functional recovery-related behavioral responses following intrathecal injection (IT) of a CD137L neutralizing antibody (αCD137L; daily day 0–7) after sciatic nerve crush (SNC) in male and female B6 mice. Mice were randomly assigned to 1 of 4 groups: no IT, PBS, 0.1 or 0.5μg of αCD137L, 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) functional recovery before surgery and on post-surgery days 1–77. On post-SNC day 1, all groups showed changes in sensitivity and decreased sensory and functional responses. By day 7, αCD137L treated mice showed reduced mechanical hypersensitivity compared to no IT and PBS-treated controls and were at baseline levels by day 42, about 1–2 weeks earlier than both control groups. All groups showed hyposensitivity to heat stimulus on day 1, but quickly returned to baseline with no group differences. On days 1–35 hyposensitivity to a cold stimulus was also found in all groups, but αCD137Ltreated mice were slightly more sensitive on days 49–77. Grip strength improved in all groups on day 14 without significant group differences. On days 3–14, αCD137L-treated groups had higher toe space scores compared to controls. Finally, sensory recovery (pin prick) in αCD137L-treated groups emerged on day 3, a week earlier than the control groups. Together, our results suggest that CD137L likely contributes to sensory hypersensitivity and functional changes early on following peripheral nervy injury.