Progress in mechanism of passive exercise and denervated muscular atrophy_West China Medical Journal

Authors：

WANG Yan ¹ , GUO Xiaojing ² , WANG Yan ³ ,  QIAN Chunsheng ¹

1. Department of Rehabilitation Medicine, the 962nd Hospital of the Chinese People’s Liberation Army Joint Logistics Support Force, Harbin, Heilongjiang 150006, P. R. China;
2. Second Clinical Medical College, Shanxi University of Traditional Chinese Medicine, Jinzhong, Shanxi 030619, P. R. China;
3. Rehabilitation Center, the Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150001, P. R. China;

Corresponding?author：

QIAN Chunsheng, Email: ydkf@hrbipe.edu.cn

Keywords：

Passive exercise; rehabilitation; denervation; muscular atrophy; mechanism

DOI：

10.7507/1002-0179.202509302

Video：

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Abstract Full text Figures/Tables Video References Cited by

Denervated muscle atrophy is a common complication in patients with nerve injury and neuromuscular diseases. Its mechanism involves multiple factors such as the regulation of neurotrophic factors, imbalance of protein synthesis and degradation, inflammatory response, oxidative stress, and changes in vascular microenvironment. As a non-invasive rehabilitation intervention, passive movement has shown important potential in delaying the atrophy of denervated muscle and promoting the recovery of neuromuscular function. Compared with active exercise, passive exercise activates neural pathways with a “bottom-up” sensory feedback pathway, which can maintain residual neural connections without increasing the nerve burden, reduce inflammation, and improve local circulation and psychological state through rhythmic mechanical stimulation. However, there are still some limitations in the relevant mechanism research, such as unclear specificity, weak clinical evidence, and lack of individualized regimen parameters. This article systematically reviews the physiological and molecular mechanisms, psychological regulation mechanisms, and clinical application status of passive movement intervention for denervated muscle atrophy, and integrates the physiological-psychological synergy pathway, aiming to provide systematic theoretical support and practical reference for the rehabilitation intervention of denervated muscle atrophy.

Citation： WANG Yan, GUO Xiaojing, WANG Yan, QIAN Chunsheng. Progress in mechanism of passive exercise and denervated muscular atrophy. West China Medical Journal, 2026, 41(6): 1021-1026. doi: 10.7507/1002-0179.202509302 Copy

1.	Yokogawa A, Kido K, Miura I, et al. Low-carbohydrate diet exacerbates denervation-induced atrophy of rat skeletal muscle under the condition of identical protein intake. J Cachexia Sarcopenia Muscle, 2025, 16(2): e13738.
2.	Dos Santos M, Bezprozvannaya S, McAnally JR, et al. A mechanistic basis of fast myofiber vulnerability to neuromuscular diseases. Cell Rep, 2025, 44(7): 115959.
3.	Suenaga T, Matsushima S, Masunaga T, et al. O-GlcNAcase inhibitor improves denervation-induced muscle atrophy in mice. J Cachexia Sarcopenia Muscle, 2025, 16(5): e70066.
4.	Zhang X, Xie L, Liu W, et al. Exoskeleton-guided passive movement elicits standardized EEG patterns for generalizable BCIs in stroke rehabilitation. J Neuroeng Rehabil, 2025, 22(1): 97.
5.	Petermann-Rocha F, Balntzi V, Gray SR, et al. Global prevalence of sarcopenia and severe sarcopenia: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle, 2022, 13(1): 86-99.
6.	Tari B, Heath M, Herold F, et al. Leveraging passive exercise to support brain health. Br J Sports Med, 2025, 59(3): 143-145.
7.	Onishi H. Cortical excitability following passive movement. Phys Ther Res, 2018, 21(2): 23-32.
8.	Hong CM, Jid LQ, Yee Esther CW. Effectiveness of continuous passive motion in total knee replacement patients with slow rehabilitation under ERAS pathway. J Orthop Trauma Rehabil, 2023, 30(1): 22104917221150532.
9.	Hao Z, Huo Z, Aixin-Jueluo Q, et al. Overexpression of EGFL7 promotes angiogenesis and nerve regeneration in peripheral nerve injury. Cell Biol Int, 2024, 48(11): 1698-1713.
10.	Grzelak N, Krutki P, B?czyk M, et al. Influence of altered serum and muscle concentrations of BDNF on electrophysiological properties of spinal motoneurons in wild-type and BDNF-knockout rats. Sci Rep, 2023, 13(1): 4571.
11.	Xu Q, Li Z, Su J, et al. Body weight support treadmill training combined with sciatic nerve electrical stimulation ameliorating motor function by enhancing PI3K/Akt proteins expression via BDNF/TrkB signaling pathway in rats with spinal cord injury. World Neurosurg, 2023, 178: e239-e253.
12.	Bai CH, Alizargar J, Peng CY, et al. Combination of exercise training and resveratrol attenuates obese sarcopenia in skeletal muscle atrophy. Chin J Physiol, 2020, 63(3): 101-112.
13.	楊璇, 李憲, 張鵬, 等. 被動運動對脊髓損傷大鼠后肢運動功能及骨骼肌的影響. 中國臨床解剖學雜志, 2018, 36(3): 299-303.
14.	Hu W, Huang Y, Yin W, et al. RUNX1 promotes denervation-induced muscle atrophy by activating the JUNB/NF-κB pathway and driving M1 macrophage polarization. Open Life Sci, 2025, 20(1): 20251157.
15.	Zhang N, Zhai L, Wong RMY, et al. Harnessing immunomodulation to combat sarcopenia: current insights and possible approaches. Immun Ageing, 2024, 21(1): 55.
16.	王艷, 王雅慧, 王艷, 等. TNF-α 和 IL-6 對胎兒生長受限胎兒骨骼肌的影響. 國際婦產科學雜志, 2024, 51(2): 161-166.
17.	Wu C, Tang L, Ni X, et al. Salidroside attenuates denervation-induced skeletal muscle atrophy through negative regulation of pro-inflammatory cytokine. Front Physiol, 2019, 10: 665.
18.	Mussbacher M, Derler M, Basílio J, et al. NF-κB in monocytes and macrophages - an inflammatory master regulator in multitalented immune cells. Front Immunol, 2023, 14: 1134661.
19.	Li F, Yin C, Ma Z, et al. PHD3 mediates denervation skeletal muscle atrophy through Nf-κB signal pathway. FASEB J, 2021, 35(4): e21444.
20.	Braun TP, Zhu X, Szumowski M, et al. Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic-pituitary-adrenal axis. J Exp Med, 2011, 208(12): 2449-2463.
21.	Huang Z, Zhong L, Zhu J, et al. Inhibition of IL-6/JAK/STAT3 pathway rescues denervation-induced skeletal muscle atrophy. Ann Transl Med, 2020, 8(24): 1681.
22.	Parveen A, Bohnert KR, Tomaz da Silva M, et al. MyD88-mediated signaling intercedes in neurogenic muscle atrophy through multiple mechanisms. FASEB J, 2021, 35(8): e21821.
23.	Li T, Yin D, Shi R. Gut-muscle axis mechanism of exercise prevention of sarcopenia. Front Nutr, 2024, 11: 1418778.
24.	Nukolova NV, Aleksashkin AD, Abakumova TO, et al. Multilayer polyion complex nanoformulations of superoxide dismutase 1 for acute spinal cord injury. J Control Release, 2018, 270: 226-236.
25.	Wang S, Yang X, Liu K, et al. Therapeutic potential of omaveloxolone in counteracting muscle atrophy post-denervation: a multi-omics approach. J Transl Med, 2024, 22: 991.
26.	Xu X, Zhang CJ, Talifu Z, et al. The effect of glycine and N-acetylcysteine on oxidative stress in the spinal cord and skeletal muscle after spinal cord injury. Inflammation, 2024, 47(2): 557-571.
27.	Shen Y, Zhang Q, Huang Z, et al. Isoquercitrin delays denervated soleus muscle atrophy by inhibiting oxidative stress and inflammation. Front Physiol, 2020, 11: 988.
28.	Zhang D, Cao L, Wang Z, et al. Salidroside mitigates skeletal muscle atrophy in rats with cigarette smoke-induced COPD by up-regulating myogenin and down-regulating myostatin expression. Biosci Rep, 2019, 39(11): BSR20190440.
29.	Fornelli C, Beltrà M, Zorzano A, et al. BNIP3 downregulation ameliorates muscle atrophy in cancer cachexia. Cancers (Basel), 2024, 16(24): 4133.
30.	Xie G, Jin H, Mikhail H, et al. Autophagy in sarcopenia: possible mechanisms and novel therapies. Biomed Pharmacother, 2023, 165: 115147.
31.	Wang M, Wu X, Jiao Y, et al. Life-long aerobic exercise is a non-pharmacological approach for inducing autophagy and delaying muscle atrophy in the aging population. Aging Dis, 2024, 16(4): 1842-1852.
32.	Triolo M, Hood DA. Manifestations of age on autophagy, mitophagy and lysosomes in skeletal muscle. Cells, 2021, 10(5): 1054.
33.	Ma H, Jing Y, Zeng J, et al. Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate muscle atrophy via the miR-132-3p/FoxO3 axis. J Orthop Translat, 2024, 49: 23-36.
34.	Tomaz Da Silva M, Joshi AS, Koike TE, et al. Targeted ablation of Fn14 receptor improves exercise capacity and inhibits neurogenic muscle atrophy. FASEB J, 2022, 36(12): e22666.
35.	Yang X, Xue P, Yuan M, et al. SESN2 protects against denervated muscle atrophy through unfolded protein response and mitophagy. Cell Death Dis, 2021, 12(9): 805.
36.	黃靖, 任亞鋒, 尚文雅, 等. 脊髓損傷后微循環的調控機制及治療策略. 解放軍醫學雜志, 2025, 50(3): 358-365.
37.	Delbono O, Rodrigues ACZ, Bonilla HJ, et al. The emerging role of the sympathetic nervous system in skeletal muscle motor innervation and sarcopenia. Ageing Res Rev, 2021, 67: 101305.
38.	He Z, Song Q, Yu Y, et al. Protein therapy of skeletal muscle atrophy and mechanism by angiogenic factor AGGF1. J Cachexia Sarcopenia Muscle, 2023, 14(2): 978-991.
39.	Lin H, Ma X, Sun Y, et al. Decoding the transcriptome of denervated muscle at single-nucleus resolution. J Cachexia Sarcopenia Muscle, 2022, 13(4): 2102-2117.
40.	Nasrallah FA, Mohamed AZ, Campbell ME, et al. Functional connectivity of brain associated with passive range of motion exercise: proprioceptive input promoting motor activation?. NeuroImage, 2019, 202: 116023.
41.	Wright S, Chiocchia V, Elugbadebo O, et al. The therapeutic potential of exercise in post-traumatic stress disorder and its underlying mechanisms: a living systematic review of human and non-human studies. Wellcome Open Res, 2025, 9: 720.
42.	Tays G, Bao S, Javidialsaadi M, et al. Consolidation of use-dependent motor memories induced by passive movement training. Neurosci Lett, 2020, 732: 135080.
43.	Doherty CJ, Incognito AV, Notay K, et al. Muscle sympathetic nerve responses to passive and active one-legged cycling: insights into the contributions of central command. Am J Physiol Heart Circ Physiol, 2018, 314(1): H3-H10.
44.	Han X, Ashraf M, Tipparaju SM, et al. Muscle-brain crosstalk in cognitive impairment. Front Aging Neurosci, 2023, 15: 1221653.
45.	Inoue DS, Janini Gomes M. Integrative insights into PNI: low-grade chronic inflammation, skeletal muscle wasting, and brain impairments. Brain Behav Immun Health, 2024, 40: 100838.
46.	周朝昀. 運動誘導神經可塑性生物學機制的研究進展. 國際精神病學雜志, 2023, 50(2): 210-214.
47.	Muccioli GG, Naslain D, B?ckhed F, et al. The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol, 2010, 6: 392.
48.	Jakubiec-Puka A, S?awińska U, Redowicz MJ, et al. Influence of locomotor training on the structure and myosin heavy chains of the denervated rat soleus muscle. Neurol Res, 2008, 30(2): 170-178.
49.	王世楊, 孫慧哲, 顏南, 等. 被動訓練促進失神經肌萎縮模型大鼠骨骼肌結構和功能的恢復. 中國組織工程研究, 2020, 24(32): 5138-5144.
50.	Gorgey AS, Lai RE, Khalil RE, et al. Neuromuscular electrical stimulation resistance training enhances oxygen uptake and ventilatory efficiency independent of mitochondrial complexes after spinal cord injury: a randomized clinical trial. J Appl Physiol, 2021, 131(1): 265-276.
51.	Nardone R, Orioli A, Golaszewski S, et al. Passive cycling in neurorehabilitation after spinal cord injury: a review. J Spinal Cord Med, 2017, 40(1): 8-16.
52.	Franz A, Hei? L, Schlotmann M, et al. Passive blood-flow-restriction exercise’s impact on muscle atrophy post-total knee replacement: a randomized trial. J Clin Med, 2025, 14(15): 5218.

1. Yokogawa A, Kido K, Miura I, et al. Low-carbohydrate diet exacerbates denervation-induced atrophy of rat skeletal muscle under the condition of identical protein intake. J Cachexia Sarcopenia Muscle, 2025, 16(2): e13738.
2. Dos Santos M, Bezprozvannaya S, McAnally JR, et al. A mechanistic basis of fast myofiber vulnerability to neuromuscular diseases. Cell Rep, 2025, 44(7): 115959.
3. Suenaga T, Matsushima S, Masunaga T, et al. O-GlcNAcase inhibitor improves denervation-induced muscle atrophy in mice. J Cachexia Sarcopenia Muscle, 2025, 16(5): e70066.
4. Zhang X, Xie L, Liu W, et al. Exoskeleton-guided passive movement elicits standardized EEG patterns for generalizable BCIs in stroke rehabilitation. J Neuroeng Rehabil, 2025, 22(1): 97.
5. Petermann-Rocha F, Balntzi V, Gray SR, et al. Global prevalence of sarcopenia and severe sarcopenia: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle, 2022, 13(1): 86-99.
6. Tari B, Heath M, Herold F, et al. Leveraging passive exercise to support brain health. Br J Sports Med, 2025, 59(3): 143-145.
7. Onishi H. Cortical excitability following passive movement. Phys Ther Res, 2018, 21(2): 23-32.
8. Hong CM, Jid LQ, Yee Esther CW. Effectiveness of continuous passive motion in total knee replacement patients with slow rehabilitation under ERAS pathway. J Orthop Trauma Rehabil, 2023, 30(1): 22104917221150532.
9. Hao Z, Huo Z, Aixin-Jueluo Q, et al. Overexpression of EGFL7 promotes angiogenesis and nerve regeneration in peripheral nerve injury. Cell Biol Int, 2024, 48(11): 1698-1713.
10. Grzelak N, Krutki P, B?czyk M, et al. Influence of altered serum and muscle concentrations of BDNF on electrophysiological properties of spinal motoneurons in wild-type and BDNF-knockout rats. Sci Rep, 2023, 13(1): 4571.
11. Xu Q, Li Z, Su J, et al. Body weight support treadmill training combined with sciatic nerve electrical stimulation ameliorating motor function by enhancing PI3K/Akt proteins expression via BDNF/TrkB signaling pathway in rats with spinal cord injury. World Neurosurg, 2023, 178: e239-e253.
12. Bai CH, Alizargar J, Peng CY, et al. Combination of exercise training and resveratrol attenuates obese sarcopenia in skeletal muscle atrophy. Chin J Physiol, 2020, 63(3): 101-112.
13. 楊璇, 李憲, 張鵬, 等. 被動運動對脊髓損傷大鼠后肢運動功能及骨骼肌的影響. 中國臨床解剖學雜志, 2018, 36(3): 299-303.
14. Hu W, Huang Y, Yin W, et al. RUNX1 promotes denervation-induced muscle atrophy by activating the JUNB/NF-κB pathway and driving M1 macrophage polarization. Open Life Sci, 2025, 20(1): 20251157.
15. Zhang N, Zhai L, Wong RMY, et al. Harnessing immunomodulation to combat sarcopenia: current insights and possible approaches. Immun Ageing, 2024, 21(1): 55.
16. 王艷, 王雅慧, 王艷, 等. TNF-α 和 IL-6 對胎兒生長受限胎兒骨骼肌的影響. 國際婦產科學雜志, 2024, 51(2): 161-166.
17. Wu C, Tang L, Ni X, et al. Salidroside attenuates denervation-induced skeletal muscle atrophy through negative regulation of pro-inflammatory cytokine. Front Physiol, 2019, 10: 665.
18. Mussbacher M, Derler M, Basílio J, et al. NF-κB in monocytes and macrophages - an inflammatory master regulator in multitalented immune cells. Front Immunol, 2023, 14: 1134661.
19. Li F, Yin C, Ma Z, et al. PHD3 mediates denervation skeletal muscle atrophy through Nf-κB signal pathway. FASEB J, 2021, 35(4): e21444.
20. Braun TP, Zhu X, Szumowski M, et al. Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic-pituitary-adrenal axis. J Exp Med, 2011, 208(12): 2449-2463.
21. Huang Z, Zhong L, Zhu J, et al. Inhibition of IL-6/JAK/STAT3 pathway rescues denervation-induced skeletal muscle atrophy. Ann Transl Med, 2020, 8(24): 1681.
22. Parveen A, Bohnert KR, Tomaz da Silva M, et al. MyD88-mediated signaling intercedes in neurogenic muscle atrophy through multiple mechanisms. FASEB J, 2021, 35(8): e21821.
23. Li T, Yin D, Shi R. Gut-muscle axis mechanism of exercise prevention of sarcopenia. Front Nutr, 2024, 11: 1418778.
24. Nukolova NV, Aleksashkin AD, Abakumova TO, et al. Multilayer polyion complex nanoformulations of superoxide dismutase 1 for acute spinal cord injury. J Control Release, 2018, 270: 226-236.
25. Wang S, Yang X, Liu K, et al. Therapeutic potential of omaveloxolone in counteracting muscle atrophy post-denervation: a multi-omics approach. J Transl Med, 2024, 22: 991.
26. Xu X, Zhang CJ, Talifu Z, et al. The effect of glycine and N-acetylcysteine on oxidative stress in the spinal cord and skeletal muscle after spinal cord injury. Inflammation, 2024, 47(2): 557-571.
27. Shen Y, Zhang Q, Huang Z, et al. Isoquercitrin delays denervated soleus muscle atrophy by inhibiting oxidative stress and inflammation. Front Physiol, 2020, 11: 988.
28. Zhang D, Cao L, Wang Z, et al. Salidroside mitigates skeletal muscle atrophy in rats with cigarette smoke-induced COPD by up-regulating myogenin and down-regulating myostatin expression. Biosci Rep, 2019, 39(11): BSR20190440.
29. Fornelli C, Beltrà M, Zorzano A, et al. BNIP3 downregulation ameliorates muscle atrophy in cancer cachexia. Cancers (Basel), 2024, 16(24): 4133.
30. Xie G, Jin H, Mikhail H, et al. Autophagy in sarcopenia: possible mechanisms and novel therapies. Biomed Pharmacother, 2023, 165: 115147.
31. Wang M, Wu X, Jiao Y, et al. Life-long aerobic exercise is a non-pharmacological approach for inducing autophagy and delaying muscle atrophy in the aging population. Aging Dis, 2024, 16(4): 1842-1852.
32. Triolo M, Hood DA. Manifestations of age on autophagy, mitophagy and lysosomes in skeletal muscle. Cells, 2021, 10(5): 1054.
33. Ma H, Jing Y, Zeng J, et al. Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate muscle atrophy via the miR-132-3p/FoxO3 axis. J Orthop Translat, 2024, 49: 23-36.
34. Tomaz Da Silva M, Joshi AS, Koike TE, et al. Targeted ablation of Fn14 receptor improves exercise capacity and inhibits neurogenic muscle atrophy. FASEB J, 2022, 36(12): e22666.
35. Yang X, Xue P, Yuan M, et al. SESN2 protects against denervated muscle atrophy through unfolded protein response and mitophagy. Cell Death Dis, 2021, 12(9): 805.
36. 黃靖, 任亞鋒, 尚文雅, 等. 脊髓損傷后微循環的調控機制及治療策略. 解放軍醫學雜志, 2025, 50(3): 358-365.
37. Delbono O, Rodrigues ACZ, Bonilla HJ, et al. The emerging role of the sympathetic nervous system in skeletal muscle motor innervation and sarcopenia. Ageing Res Rev, 2021, 67: 101305.
38. He Z, Song Q, Yu Y, et al. Protein therapy of skeletal muscle atrophy and mechanism by angiogenic factor AGGF1. J Cachexia Sarcopenia Muscle, 2023, 14(2): 978-991.
39. Lin H, Ma X, Sun Y, et al. Decoding the transcriptome of denervated muscle at single-nucleus resolution. J Cachexia Sarcopenia Muscle, 2022, 13(4): 2102-2117.
40. Nasrallah FA, Mohamed AZ, Campbell ME, et al. Functional connectivity of brain associated with passive range of motion exercise: proprioceptive input promoting motor activation?. NeuroImage, 2019, 202: 116023.
41. Wright S, Chiocchia V, Elugbadebo O, et al. The therapeutic potential of exercise in post-traumatic stress disorder and its underlying mechanisms: a living systematic review of human and non-human studies. Wellcome Open Res, 2025, 9: 720.
42. Tays G, Bao S, Javidialsaadi M, et al. Consolidation of use-dependent motor memories induced by passive movement training. Neurosci Lett, 2020, 732: 135080.
43. Doherty CJ, Incognito AV, Notay K, et al. Muscle sympathetic nerve responses to passive and active one-legged cycling: insights into the contributions of central command. Am J Physiol Heart Circ Physiol, 2018, 314(1): H3-H10.
44. Han X, Ashraf M, Tipparaju SM, et al. Muscle-brain crosstalk in cognitive impairment. Front Aging Neurosci, 2023, 15: 1221653.
45. Inoue DS, Janini Gomes M. Integrative insights into PNI: low-grade chronic inflammation, skeletal muscle wasting, and brain impairments. Brain Behav Immun Health, 2024, 40: 100838.
46. 周朝昀. 運動誘導神經可塑性生物學機制的研究進展. 國際精神病學雜志, 2023, 50(2): 210-214.
47. Muccioli GG, Naslain D, B?ckhed F, et al. The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol, 2010, 6: 392.
48. Jakubiec-Puka A, S?awińska U, Redowicz MJ, et al. Influence of locomotor training on the structure and myosin heavy chains of the denervated rat soleus muscle. Neurol Res, 2008, 30(2): 170-178.
49. 王世楊, 孫慧哲, 顏南, 等. 被動訓練促進失神經肌萎縮模型大鼠骨骼肌結構和功能的恢復. 中國組織工程研究, 2020, 24(32): 5138-5144.
50. Gorgey AS, Lai RE, Khalil RE, et al. Neuromuscular electrical stimulation resistance training enhances oxygen uptake and ventilatory efficiency independent of mitochondrial complexes after spinal cord injury: a randomized clinical trial. J Appl Physiol, 2021, 131(1): 265-276.
51. Nardone R, Orioli A, Golaszewski S, et al. Passive cycling in neurorehabilitation after spinal cord injury: a review. J Spinal Cord Med, 2017, 40(1): 8-16.
52. Franz A, Hei? L, Schlotmann M, et al. Passive blood-flow-restriction exercise’s impact on muscle atrophy post-total knee replacement: a randomized trial. J Clin Med, 2025, 14(15): 5218.

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