Pain Modulation, Inflammation-Regulatory Mechanisms, and Translational Boundaries of Evidence for Acupuncture-Related Therapies in Knee Osteoarthritis: A Structured Narrative Review.

Background: Knee osteoarthritis is a common whole-joint disorder characterized by pain, functional limitation, cartilage degeneration, synovial inflammation, and subchondral bone remodeling. Acupuncture-related therapies are used as adjunctive nonpharmacological options, but their clinical role and biological interpretation require cautious assessment. Methods: A structured narrative search of PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and the Chinese Science and Technology Periodical Database was conducted through 31 May 2026. Clinical studies, evidence syntheses, guidelines, protocols, and preclinical studies were included when relevant to pain modulation, inflammation-related mechanisms, clinical efficacy, safety, or translational interpretation. Evidence was categorized as clinical evidence, guideline-based positioning, preclinical mechanistic evidence, research-design evidence, or translational limitation evidence. Results: Clinical evidence suggests that acupuncture-related interventions may provide short-term pain relief and functional improvement in some patients with knee osteoarthritis, although durability, effect size, and technique-specific superiority remain uncertain. Manual acupuncture, electroacupuncture, warm needle acupuncture, fire needling, acupuncture knife therapy, laser acupuncture, and combined regimens differ in stimulation mode, treatment dose, safety profile, and evidence strength. Preclinical studies suggest associations with synovial inflammation, cytokine networks, oxidative stress, autophagy, apoptosis, pyroptosis, cartilage matrix metabolism, neuroimmune regulation, and gut microbiota-related pathways. However, most mechanistic findings are derived from animal or cell models and should be interpreted as biological hypotheses rather than confirmed human causal mechanisms. Conclusion: Acupuncture-related therapies may be considered complementary options within individualized knee osteoarthritis management, but they should not replace education, exercise, weight control, pharmacological treatment, or surgery when indicated. Future studies should integrate standardized reporting, robust comparators, adequate follow-up, objective inflammatory biomarkers, imaging findings, pain phenotyping, and safety monitoring to clarify which patients may benefit most.