Repetitive transcranial magnetic stimulation modulates neuroinflammation and cell apoptosis via the interaction between Ifit3 and Stat1 for the treatment of neuropathic pain

Inflamm Res. 2026 Mar 22;75(1):68. doi: 10.1007/s00011-026-02212-x.

ABSTRACT

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS), a non-invasive electrophysiological technique employed in the treatment of neuropathic pain (NeuP), still has an elusive therapeutic mechanism.

METHODS: In this study, transcriptomic and proteomic analyses were carried out on the brain tissues of rats with chronic constriction injury (CCI) models. Particular emphasis was placed on the key regulatory molecule Ifit3 and its interacting protein Stat1.

RESULTS: Findings revealed that rTMS was capable of significantly ameliorating the elevated expression levels of Ifit3 and Stat1 in the brain tissues of NeuP rats. Moreover, in in-vitro experiments, rTMS effectively mitigated the neuroinflammatory response and the degree of microglial apoptosis. Further investigations demonstrated that overexpressing Ifit3 led to an exacerbation of the aforementioned inflammation and apoptosis related manifestations. Conversely, silencing Ifit3 had a mitigating effect. Additionally, a high degree of consistency was observed in the expression changes of Stat1 and Ifit3.

CONCLUSIONS: Collectively, these research outcomes indicate that rTMS exerts its therapeutic effect on NeuP by modulating the inflammatory response and cell apoptosis. During this process, the interaction between Ifit3 and Stat1 assumes a pivotal regulatory role.

PMID:41865234 | DOI:10.1007/s00011-026-02212-x