Contributions of SARM1 to neuropathic pain vary across nerve injury models

The purpose of this study is to determine if Sarm1 is required for the development of nerve injury induced neuropathic pain. Neuropathic pain after nerve injury often manifests as mechanical allodynia and thermal hyperalgesia. Wallerian degeneration has been reported to play a role in the development of nerve injury induced neuropathic pain. In addition, sterile alpha and TIR motif containing 1 (Sarm1) is a protein required for Wallerian degeneration and has been implicated in several non-axotomy neuropathic pain models. It is thus of our interest to determine the requirement of Sarm1 for the development of nerve injury induced neuropathic pain. Either the spared nerve injury (SNI), L4 Spinal Nerve Ligation (SNL), or chronic constriction injury (CCI) nerve injury model was performed on Sarm1KO mice and their littermate WT controls. Behavioral assays of evoked mechanical (von Frey, dynamic brush) and thermal (Hargreaves) sensitivity were performed at multiple time points before and after surgery to assess pain sensitivity. Alternatively, mice were videorecorded after injury and their spontaneous pain-related behaviors scored. Results Sarm1KO mice did not exhibit deficits in development of punctate or dynamic brush mechanical allodynia after CCI. Interestingly, however, Sarm1KO did exhibit a delay in development of heat hyperalgesia after CCI compared to WT controls. By contrast, Sarm1KO mice did not show deficits in development of either mechanical allodynia or thermal hyperalgesia after SNI and L4 SNL surgeries. However, preliminary results suggest a trend towards reduced spontaneous pain behaviors after SNI in SARM1 KO, compared to WT controls. Our data suggest that Sarm1 is required for the normal development of heat hyperalgesia but not mechanical allodynia after CCI. In summary, the role of Sarm1 in nerve injury induced neuropathic pain is both model and modality dependent. Grant support from Neurosurgery Pain Research Institute at Johns Hopkins Dr. Miriam and Sheldon Adelson Medical Research Foundation.