Swimming exercise may alleviate neuropathic pain (NP) in spared nerve injury (SNI) mice by regulating pain-related genes, such as miR-183 and Cacna2d2. However, the related upstream mechanism remains unclear. The demethylase fat-mass and obesity-associated protein (FTO) in the dorsal root ganglia (DRG) participates in NP through m6A modification. However, whether FTO-regulated m6A modification contributes to the analgesic effect of swimming remains unknown. This study aimed to investigate the influence of swimming on FTO expression in the DRG of SNI mice and clarify its role in regulating the m6A modification of miR-183 by inhibiting FTO expression. We established a male SNI mouse model, performed intrathecal injections of adeno-associated viruses to knock down or overexpress FTO, and manipulated the expression of FTO in male and female miR-183 knockout mice. In addition, we subjected the above models to six weeks of swimming training and analyzed the effects on pain behavior, m6A modification levels, and the expression of target gene transcription and protein levels. We observed that swimming exercise downregulated FTO mRNA and protein expressions in the injured L4–L6 DRGs of SNI mice, promoted the m6A modification of miR-183, and showed an association with the increased expression levels of miR-183. These outcomes further reduced the downstream target gene Cacna2d2 and the BDNF/TrkB signaling pathway, which alleviated mechanical and cold allodynia. This study suggested that swimming exercise alleviates NP, potentially by downregulating FTO and promoting m6A methylation of miR-183. FTO-regulated m6A modification plays a key role in the mechanism of exercise-induced analgesia. Swimming exercise alleviates allodynia in peripheral nerve injury-induced NP, potentially by downregulating FTO and promoting the m6A methylation of miR-183, which reduces the downstream target genes Cacna2d2 and BDNF/TrkB.

Objective: This exploratory study aimed to evaluate the effects of electroacupuncture (EA) on pain and functional outcomes in patients with chronic nonspecific low back pain (CNLBP), and to investigate objective peripheral physiological responses associated with clinical improvement. Methods: In this prospective, double-blind, randomized sham-controlled trial, adults with CNLBP received EA at Shenshu (BL23) and an ipsilateral Ashi acupoint three times weekly for 2 weeks, followed by a 4-week follow-up. The primary outcome was pain intensity assessed by the Numeric Rating Scale (NRS), with responder analysis based on the minimal clinically important difference (MCID; ΔNRS ≥ 2). Secondary outcomes included the Oswestry Disability Index (ODI), local microcirculatory perfusion, skin temperature, and muscle tissue properties. Results: Compared with sham EA, EA significantly reduced pain intensity after the first session, after six sessions, and at follow-up (p < 0.003; r = 0.70–0.84). MCID responder rates were significantly higher in the EA group after the first session, six sessions and at follow-up (p < 0.003; RR = 3.75 and 6.00 after six sessions and follow-up, respectively). EA increased local blood flow at BL23 after the first and sixth sessions. Skin temperature showed only a transient within-group increase, without a significant adjusted between-group difference. Similar trends were observed at Ashi acupoint, and increased blood flow was associated with pain improvement. Conclusions: EA improved pain and functional outcomes in patients with CNLBP while inducing measurable peripheral vascular and physiological responses. Increased local blood flow may represent a candidate physiological correlate of EA-related symptom improvement. These findings support the exploration of objective physiological markers in acupuncture research.