Functional Recovery after Peripheral Nerve Injury is Dependent on the Pro-Inflammatory Cytokines IL-1β and TNF: Implications for Neuropathic Pain

摘要: IL-1β and TNF are potential targets in the management of neuropathic pain after injury. However, importance IL-1 systems for peripheral nerve regeneration mechanisms by which these cytokines mediate effects to be fully elucidated. Here, we demonstrate that mRNA protein levels rapidly upregulated injured mouse sciatic nerve. Mice lacking both TNF, or type 1 receptor (IL-1R1) (TNFR1), showed reduced nociceptive sensitivity (mechanical allodynia) compared with wild-type littermates Microinjecting recombinant at site injury IL-1β- TNF-knock-out mice restored mechanical thresholds back observed mice. Importantly, recovery function was impaired IL-1β-, TNF-, IL-1β/TNF-knock-out Notably, infiltration neutrophils almost completely prevented distal stump IL-1R1 TNFR1. Systemic treatment an anti-Ly6G antibody deplete neutrophils, cells play essential role genesis pain, did not affect neurological axon regeneration. Together, results suggest targeting specific IL-1β/TNF-dependent responses, such as neutrophil infiltration, is a better therapeutic strategy than complete blockage cytokine production.