- 1. Department of Rehabilitation Medicine, Yingshan Hospital (Yingshan County People's Hospital), West China Hospital of Sichuan University, Yingshan, Sichuan 637700, P. R. China;
- 2. Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
- 3. Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
HE Chengqi,
Email: hxkfhcq@126.com
The degree of pain in knee osteoarthritis is often inconsistent with joint structural damage. After tissue injury, pain sensitization can occur, mediated by pro-inflammatory factors enhancing neuroinflammation and nociceptive input, which triggers significant pain. Currently, low-impact aerobic exercise can inhibit neuroinflammation and enhance descending pain inhibitory pathways, thereby reducing pain; isometric resistance training, on the other hand, reduces central sensitization effects by improving central nervous system plasticity. Both are core exercises for anti-inflammation and desensitization. This article focuses on the mechanisms of neuroinflammation, emphasizing anti-inflammation, avoiding harmful movements, and promoting descending inhibitory pathways and central plasticity. Based on this, targeted intervention programs are designed to provide basis for formulating optimal exercise strategies for patients with knee osteoarthritis.
Citation： WU Yulin, HE Chengqi. Exercise selection for knee osteoarthritis based on pain sensitization mechanisms. West China Medical Journal, 2026, 41(6): 1016-1020. doi: 10.7507/1002-0179.202605041 Copy
Copyright ? the editorial department of West China Medical Journal of West China Medical Publisher. All rights reserved
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| 2. | Brandt KD, Dieppe P, Radin EL. Etiopathogenesis of osteoarthritis. Rheum Dis Clin North Am, 2008, 34(3): 531-559. |
| 3. | Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain, 2011, 152(3 Suppl): S2-S15. |
| 4. | Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature, 1983, 306(5944): 686-688. |
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| 10. | da Silva LA, Thirupathi A, Colares MC, et al. The effectiveness of treadmill and swimming exercise in an animal model of osteoarthritis. Front Physiol, 2023, 14: 1101159. |
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- 1. Dieppe PA, Lohmander LS. Pathogenesis and management of pain in osteoarthritis. Lancet, 2005, 365(9463): 965-973.
- 2. Brandt KD, Dieppe P, Radin EL. Etiopathogenesis of osteoarthritis. Rheum Dis Clin North Am, 2008, 34(3): 531-559.
- 3. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain, 2011, 152(3 Suppl): S2-S15.
- 4. Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature, 1983, 306(5944): 686-688.
- 5. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science, 2000, 288(5472): 1765-1769.
- 6. 徐子涵, 尤浩軍. 運動誘發的鎮痛效應: 脊髓、皮層下和皮層機制. 生物化學與生物物理進展, 2022, 49(3): 481-491.
- 7. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet, 2019, 393(10182): 1745-1759.
- 8. Sharma L. Osteoarthritis of the knee. N Engl J Med, 2021, 384(1): 51-59.
- 9. Hu HY, Jia LN, Zhao WY, et al. Clinical effect and mechanism of aerobic exercise for knee osteoarthritis: a mini review. Front Physiol, 2025, 16: 1708750.
- 10. da Silva LA, Thirupathi A, Colares MC, et al. The effectiveness of treadmill and swimming exercise in an animal model of osteoarthritis. Front Physiol, 2023, 14: 1101159.
- 11. Zhao Z, Wang R, Guo Y, et al. Static low-angle squatting reduces the intra-articular inflammatory cytokines and improves the performance of patients with knee osteoarthritis. Biomed Res Int, 2019, 2019: 9617923.
- 12. Huston P. Why osteoarthritis of the knee is called “a wound that does not heal” and why Tai Chi is an effective treatment. Front Med (Lausanne), 2023, 10: 1208326.
- 13. Liu Z, Li M, Zhang L, et al. NGF signaling exacerbates KOA peripheral hyperalgesia via the increased TRPV1-labeled synovial sensory innervation in KOA rats. Pain Res Manag, 2024, 2024: 1552594.
- 14. Cha M, Bak H, Lee BH, et al. Alleviation of peripheral sensitization by quadriceps insertion of cog polydioxanone filaments in knee osteoarthritis rats. Biochem Biophys Res Commun, 2024, 698: 149549.
- 15. Morgan M, Nazemian V, Ooi LS, et al. Artemin sensitizes nociceptors that innervate the osteoarthritic joint to produce pain. Osteoarthritis Cartilage, 2023, 31(10): 1342-1352.
- 16. 李奇堯, 何晨暢, 黃銳, 等. 機械性疼痛在膝骨關節炎中的研究進展. 中華骨與關節外科雜志, 2024, 17(6): 573-580.
- 17. Ohashi Y, Uchida K, Fukushima K, et al. Mechanisms of peripheral and central sensitization in osteoarthritis pain. Cureus, 2023, 15(2): e35331.
- 18. Puts S, Njemini R, Bilterys T, et al. Linking intra-articular inflammatory biomarkers with peripheral and central sensitization in late-stage knee osteoarthritis pain: a pilot study. J Clin Med, 2024, 13(17): 5212.
- 19. Gautam M, Yamada A, Yamada A, et al. Distinct local and global functions of Aβ low-threshold mechanoreceptors in mechanical pain transmission. Res Sq, 2023: rs.3.rs-2939309.
- 20. Sagar DR, Nwosu L, Walsh DA, et al. Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat. Osteoarthritis Cartilage, 2015, 23(6): 906-913.
- 21. Schaible HG, K?nig C, Ebersberger A. Spinal pain processing in arthritis: neuron and glia (inter) actions. J Neurochem, 2024, 168(11): 3644-3662.
- 22. 馬翠, 葉鈺娟, 嚴興科. 杏仁核介導的痛情緒神經環路研究進展. 上海交通大學學報(醫學版), 2023, 43(10): 1304-1310.
- 23. Kiritoshi T, Yakhnitsa V, Singh S, et al. Cells and circuits for amygdala neuroplasticity in the transition to chronic pain. Cell Rep, 2024, 43(9): 114669.
- 24. Li X, Huang Y, Bai J. Spinal astrocytes involved in the pathogenesis and treatment of neuropathic pain. Front Cell Neurosci, 2025, 19: 1547524.
- 25. Malek N, Mlost J, Kostrzewa M, et al. Description of novel molecular factors in lumbar DRGs and spinal cord factors underlying development of neuropathic pain component in the animal model of osteoarthritis. Mol Neurobiol, 2024, 61(3): 1580-1592.
- 26. 張祥, 董洪權, 錢燕寧. 血-腦屏障的改變在外周致中樞炎癥中的作用及其與 POCD 的關系. 北京: 第十次全國麻醉學與復蘇進展學術會議論文集, 2015: 103-106.
- 27. 闞敏慧, 王天龍. 急性系統性炎癥介導中樞性炎癥機制的研究進展. 國際麻醉學與復蘇雜志, 2018, 39(2): 188-192.
- 28. Browne TJ, Smith KM, Gradwell MA, et al. Spinoparabrachial projection neurons form distinct classes in the mouse dorsal horn. Pain, 2021, 162(7): 1977-1994.
- 29. Bai Y, Pacheco-Barrios K, Pacheco-Barrios N, et al. Neurocircuitry basis of motor cortex-related analgesia as an emerging approach for chronic pain management. Nat Ment Health, 2024, 2(5): 496-513.
- 30. Liu CH, Feng HJ, Peng F, et al. Involvement of mediodorsal thalamus and its related neural circuit in pain regulation in mice. Neurobiol Dis, 2025, 215: 107056.
- 31. Tu Y, Li Z, Zhang L. Pain-preferential thalamocortical neural dynamics across species. Nat Hum Behav, 2024, 8(1): 149-163.
- 32. Salazar-Méndez J, Cuyul-Vásquez I, Viscay-Sanhueza N, et al. Structural and functional brain changes in people with knee osteoarthritis: a scoping review. Peer J, 2023, 11: e16003.
- 33. Amodeo G, Galimberti G, Ceruti S, et al. Physical exercise ameliorates pain, mood alterations and neuroinflammation in a murine model of osteoarthritis. Life Sci, 2025, 374: 123710.
- 34. Motokawa S, Sakamoto J, Sasaki R, et al. Low-intensity muscle contraction exercise reduces pain sensitivity by modulating peripheral pathology and spinal sensitization in end-stage knee osteoarthritis rats. Front Pain Res (Lausanne), 2025, 6: 1644177.
- 35. Yang Y, Wang J, Wang T, et al. Optimal resistance training strategies for knee osteoarthritis symptom relief: a systematic review and network meta-analysis. BMC Musculoskelet Disord, 2025, 27(1): 48.
- 36. Wang Y, Jin Z, Jia S, et al. Mechanical stress protects against chondrocyte pyroptosis through TGF-β1-mediated activation of Smad2/3 and inhibition of the NF-κB signaling pathway in an osteoarthritis model. Biomed Pharmacother, 2023, 159: 114216.
- 37. 周術鋒, 王芳, 彭永, 等. 12 周太極拳聯合漸進抗阻運動對膝關節骨性關節炎患者微循環功能及炎性因子的影響. 中國體育科技, 2023, 59(3): 44-49.
- 38. 蔡任, 錢佳佳, 許奇, 等. 游泳運動對膝骨關節炎小鼠軟骨退變和 NF-κB 激活的影響. 山東體育學院學報, 2021, 37(6): 25-33.
- 39. Huang L, Du W, Jin X, et al. Swimming exercise reduces H-type vessels by down-regulating the Hif-1α/VEGFa pathway in mice with osteoarthritis of the knee. BMC Musculoskelet Disord, 2025, 26(1): 657.
- 40. 王一迪. 水中運動干預對膝關節骨關節炎癥狀影響的 Meta 分析. 北京: 北京體育大學, 2022.
- 41. Rosada M, Speciali D, Dias de Oliveira FB, et al. Eight weeks of a lower limb resistance training protocol and gait performance in patients with symptomatic mild to moderate knee osteoarthritis.J Orthop Sci, 2024, 29(4): 1037-1045.
- 42. 馮燕. 抗阻運動對高脂飲食誘導的肥胖大鼠脂肪組織自噬和炎癥因子的影響. 基因組學與應用生物學, 2020, 39(2): 867-873.
- 43. Liu W, Yin M, Li H. Optimizing resistance training for pain management in knee and hip osteoarthritis: a pairwise and dose-response meta-analysis. Front Public Health, 2025, 13: 1623679.
- 44. 錢琨, 于辰曦, 李毅, 等. 運動處方在膝骨性關節炎應用的進展. 中國矯形外科雜志, 2023, 31(19): 1773-1777.
- 45. Liao Z, Zhao S, Fang S, et al. Comparative efficacy of various exercise therapies for chronic fatigue syndrome: a systematic review and network meta-analysis. iScience, 2025, 28(12): 114178.
- 46. Yan L, Li D, Xing D, et al. Comparative efficacy and safety of exercise modalities in knee osteoarthritis: systematic review and network meta-analysis. BMJ, 2025, 391: e085242.
- 47. 劉露, 安曉妤, 歐大芳, 等. 八段錦聯合穴位按摩輔助治療對老年膝關節骨性關節炎病人血清軟骨寡聚基質蛋白、低氧誘導因子表達的影響. 循證護理, 2023, 9(9): 1668-1672.
- 48. Yu L, Tian D, Su Z, et al. Mechanical stress overload promotes NF-κB/NLRP3-mediated osteoarthritis synovitis and fibrosis through Piezo1. Cell Signal, 2025, 132: 111786.
- 49. 《中國髕股關節骨關節炎診療指南(2020 年版)》發布. 中華醫學信息導報, 2020, 35(18): 15.
- 50. Sow TTM, Hasegawa T. Neuroimmune interactions in arthritis: linking pain sensitisation and inflammation. J Bone Miner Metab, 2026, 44(2): 213-220.
- 51. Mailhot B, Christin M, Tessandier N, et al. Neuronal interleukin-1 receptors mediate pain in chronic inflammatory diseases. J Exp Med, 2020, 217(9): e20191430.
- 52. Alad M, Yousef F, Epure LM, et al. Unraveling osteoarthritis: mechanistic insights and emerging therapies targeting pain and inflammation. Biomolecules, 2025, 15(6): 874.
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