Swimming Exercise Ameliorates Neuropathic Pain and Is Associated with Hippocampal H19, miR-22, and Wnt/β-Catenin Signaling.

Physical activity is known to ameliorate neuropathic pain (NP); however, the underlying mechanisms, particularly those involving long non-coding RNAs (lncRNAs) in the hippocampus, remain poorly understood. In this study, we assessed the impact of swimming training on NP in a mouse model of sciatic nerve injury (SNI), with a focus on the lncRNA H19 and its associated signaling pathway. A male C57BL/6 mouse model of SNI was established and randomly divided into five groups: naïve, sham, sham + swim, SNI, and SNI + swim. The swimming groups underwent a 6-week training regimen. Pain thresholds were assessed at multiple time points post-modeling, and hippocampal tissues were collected on day 43 for analysis. Six weeks of swimming training significantly attenuated mechanical hypersensitivity in SNI mice. Compared with the SNI group, swimming training was associated with reduced hippocampal expression of H19, Wnt3a, and β-catenin. Histological analyses using HE and Nissl staining demonstrated improved neuronal morphology and preservation of neuronal structure in the hippocampus following swimming training. In addition, swimming training modulated hippocampal neuroinflammation, as evidenced by decreased levels of IL-6 and TNF-α and increased expression of the IL-10. These findings indicate that swimming training effectively alleviates NP and hippocampal neuroinflammation in SNI mice and is accompanied by coordinated changes in hippocampal H19, miR-22, and Wnt/β-catenin signaling. These associations suggest a potential involvement of H19-related molecular responses in exercise-mediated neuroprotection; however, further mechanistic studies are required to establish causal relationships.