EFFICACY OF LET-7E IN REDUCING NEUROPATHIC PAIN VIA DUAL TARGETING OF NAP1L1 AND IMMUNE CELL INFILTRATION IN ATHLETES

Abstract

Background: Neuropathic pain (NP) significantly hampers athletic performance and recovery, necessitating effective therapeutic strategies. MicroRNAs, particularly Let-7e, have emerged as pivotal modulators in inflammatory and neuropathic pathways. This study explores the dual impact of Let-7e on NAP1L1 modulation and immune cell dynamics in the context of athletic health and injury recovery. Materials and Methods: Utilizing both bioinformatics and experimental approaches, we investigated Let-7e expression in spinal cord injury (SCI) models and LPS-stimulated microglial BV2 cells. The study applied RT-PCR for expression analysis, TIMER datasets for immune infiltration impacts, and ELISA for cytokine profiling (IL-1β, IL-6, TNF-α). Additionally, luciferase assays and western blotting elucidated the interaction between Let-7e and its target NAP1L1. Results: Let-7e levels were notably diminished in SCI contexts, correlating with increased neuropathic pain markers. Overexpression of Let-7e significantly attenuated inflammatory cytokines in BV2 cells, highlighting its potent anti-inflammatory effects. Bioinformatics confirmed Let-7e’s suppression of NAP1L1, a protein inversely modulated in the presence of Let-7e, which also influenced various immune cells relevant to inflammation and NP. Conclusion: The interplay between Let-7e, NAP1L1, and immune cell infiltration presents a promising avenue for developing targeted therapies for neuropathic pain management in athletes. Enhancing Let-7e expression could potentially mitigate pain and expedite recovery, fostering better athletic performance and wellbeing.