A novel application of transcranial pulse stimulation in rehabilitation: pain management in refractory knee osteoarthritis – a case series
DOI:
https://doi.org/10.2340/jrm.v57.42403Keywords:
Knee Osteoarthritis, Chronic Pain, noninvasive brain stimulation, Neuromodulation, TPS, Transcranial Pulse Stimulation, refractory painAbstract
Background: Knee osteoarthritis is the most common form of arthritis in adults and a leading cause of years lived with disability. Knee osteoarthritis is a significant burden on health systems worldwide.
Objective: This study evaluated the impact of transcranial pulse stimulation in pain intensity on a case series of 8 patients with refractory pain due to primary knee osteoarthritis.
Design: Prospective before-and-after case series.
Setting: Tertiary rehabilitation outpatient clinic at a university hospital.
Methods: Transcranial pulse stimulation was delivered in 6 sessions per participant on 8 patients, diagnosed with knee osteoarthritis using the American College of Rheumatology and the Kellgren–Lawrence radiographic grading criteria, with a nominal weekly interval but an adaptive schedule that accommodated individual and logistical constraints. Overall adherence to the programme, the effect on pain level on the Visual Analogue Scale and side effects were assessed.
Results: In total, 8 female patients were evaluated for the visual analogue scale score before and after therapy. Their ages ranged from 63 to 77 years, with an average of 69.3 (± 5.3) years. The mean initial (before therapy) Visual Analogue Scale score for the right knee was 6.4 (± 2.5) across the patients, and that score reduced to an average of 1.1 (± 1.6) by the end of the therapy. Similarly, the average for the left knee reduced from 7.2 (± 1.4) to 1.4 (± 1.8). This resulted in an average reduction in pain of 5.3 points for the right knee and of 5.8 points for the left knee. All patients improved their scores. Proper adherence and tolerance to the transcranial pulse stimulation protocol was observed, with no severe side effects.
Conclusion: Transcranial pulse stimulation reduced pain in patients with refractory pain due to primary knee osteoarthritis. It may be considered as an intervention for knee osteoarthritis patients with chronic disabling pain.
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References
GBD 2021 Osteoarthritis Collaborators. Global, regional, and national burden of osteoarthritis, 1990–2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol 2023; 5: e508.
Cohen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. Lancet 2021; 397: 2082. DOI: https://doi.org/10.1016/S0140-6736(21)00393-7
Imamura M, Shinzato GT, Sugawara AT, Uchiyama SST, Ayres DVM, Simis M, et al. The Institute of Physical Medicine and Rehabilitation, Hospital das Clínicas University of São Paulo School of Medicine comprehensive rehabilitation program for elderly people with knee osteoarthritis. Front Med 2022; 9: 1029140. DOI: https://doi.org/10.3389/fmed.2022.1029140
Shinzato GT, Assone T, Sandler PC, Pacheco-Barrios K, Fregni F, Radanovic M, et al. Non-invasive sound wave brain stimulation with Transcranial Pulse Stimulation (TPS) improves neuropsychiatric symptoms in Alzheimer’s disease. Brain Stimul 2024; 17: 413. DOI: https://doi.org/10.1016/j.brs.2024.03.007
Beisteiner R, Matt E, Fan C, Baldysiak H, Schönfeld M, Philippi Novak T, et al. Transcranial pulse stimulation with ultrasound in Alzheimer’s disease: a new navigated focal brain therapy. Adv Sci (Weinh) 2019; 7: 1902583. DOI: https://doi.org/10.1002/advs.201902583
Dörl G, Matt E, Beisteiner R. Functional specificity of TPS brain stimulation effects in patients with Alzheimer’s disease: a follow-up fMRI analysis. Neurol Ther 2022; 11: 1391. DOI: https://doi.org/10.1007/s40120-022-00362-8
Cont C, Stute N, Galli A, Schulte C, Logmin K, Trenado C, et al. Retrospective real-world pilot data on transcranial pulse stimulation in mild to severe Alzheimer’s patients. Front Neurol 2022; 13: 948204. DOI: https://doi.org/10.3389/fneur.2022.948204
Sprick U, Köhne M. Brain stimulation by noninvasive transcranial pulse stimulation (TPS) improves cognitive deficits and mood in Alzheimer’s disease. Presented at 2022 International Conference on Electrical, Computer, Communications and Mechatronics Engineering (ICECCME); 2022 Maldives, Maldives. Available from: https://doi.org/10.1109/ICECCME55909.2022.9988704 DOI: https://doi.org/10.1109/ICECCME55909.2022.9988704
Fong TKH, Cheung T, Ngan STJ, Tong K, Lui WYV, Chan WC, et al. Transcranial pulse stimulation in the treatment of mild neurocognitive disorders. Ann Clin Transl Neurol 2023; 10: 1885. DOI: https://doi.org/10.1002/acn3.51882
Matt E, Dörl G, Beisteiner R. Transcranial pulse stimulation (TPS) improves depression in AD patients on state-of-the-art treatment. Alzheimers Dement (N Y) 2022; 8: e12245. DOI: https://doi.org/10.1002/trc2.12245
Chen X, You J, Ma H, Zhou M, Huang C. Transcranial pulse stimulation in Alzheimer’s disease. CNS Neurosci Ther 2024; 30: e14372. DOI: https://doi.org/10.1111/cns.14372
Fernández-Castaño R, Fernández-Blázquez MÁ, Echevarría Fernández I, Cabrera-Freitag M, Freitag K. Effect of transcranial pulse stimulation for the treatment of Alzheimer’s disease and its related symptoms. Curr Alzheimer Res 2023; 20: 244. DOI: https://doi.org/10.2174/1567205020666230727102025
Giannoni-Luza S, Pacheco-Barrios K, Cardenas-Rojas A, Mejia-Pando PF, Luna-Cuadros MA, Barouh JL, et al. Noninvasive motor cortex stimulation effects on quantitative sensory testing in healthy and chronic pain subjects: a systematic review and meta-analysis. Pain 2020; 161: 1955. DOI: https://doi.org/10.1097/j.pain.0000000000001893
Kummer K, Sheets PL. Targeting prefrontal cortex dysfunction in pain. J Pharmacol Exp Ther 2024; 389: 268. DOI: https://doi.org/10.1124/jpet.123.002046
Chaim Filho F, Imamura M, Squarzoni P, Duran FLS, Busatto Filho G, Fregni F, et al. Neuroimage of patients with severe knee osteoarthritis brain volumetric evaluation. J Int Soc Phys Rehabil Med 2020; 3: S569.
Popescu T, Pernet C, Beisteiner R. Transcranial ultrasound pulse stimulation reduces cortical atrophy in Alzheimer’s patients: a follow-up study. Alzheimers Dement (N Y) 2021; 7(1): e12121. DOI: https://doi.org/10.1002/trc2.12121
Cheung T, Li TMH, Ho YS, Kranz G, Fong KNK, Leung SF, et al. Effects of transcranial pulse stimulation (TPS) on adults with symptoms of depression: a pilot randomized controlled trial. Int J Environ Res Public Health 2023; 20: 2333. DOI: https://doi.org/10.3390/ijerph20032333
Abicalaf CARP, Nakada LN, Santos FRA, Akiho I, Santos ACA, Imamura M, et al. Ultrasonography findings in knee osteoarthritis: a prospective observational cross-sectional study of 100 patients. Sci Rep 2021; 11: 16589. DOI: https://doi.org/10.1038/s41598-021-95419-3
Barbosa SP, Marques L, Sugawara A, Toledo F, Imamura M, Battistella L, et al. Predictors of the Health-Related Quality of Life (HRQOL) in SF-36 in knee osteoarthritis patients: a multimodal model with moderators and mediators. Cureus 2022; 14: e27339.
Marques LM, Barbosa SP, Pacheco-Barrios K, Goncalves FT, Imamura M, Battistella LR, et al. Motor event-related synchronization as an inhibitory biomarker of pain severity, sensitivity, and chronicity in patients with knee osteoarthritis. Neurophysiol Clin 2022; 52: 413. DOI: https://doi.org/10.1016/j.neucli.2022.09.006
Simis M, Imamura M, Pacheco-Barrios K, Marduy A, Melo PS, Mendes AJ, et al. EEG theta and beta bands as brain oscillations for different knee osteoarthritis phenotypes according to disease severity. Sci Rep 2022; 12: 1480. DOI: https://doi.org/10.1038/s41598-022-04957-x
Simis M, Pacheco-Barrios K, Vasquez-Avila K, Rebello-Sanchez I, Parente J, Castelo-Branco L, et al. Functional and neural correlates associated with conditioned pain modulation in patients with chronic knee osteoarthritis pain: a cross-sectional study. Life (Basel) 2023; 13: 1697. DOI: https://doi.org/10.3390/life13081697
Imamura M, Rebello-Sanchez I, Parente J, Marduy A, Vasquez-Avila K, Pacheco-Barrios K, et al. Factors associated with pain pressure threshold in both local and remote sites in knee osteoarthritis. PM R 2024; 16: 132. DOI: https://doi.org/10.1002/pmrj.13038
Marques LM, Castellani A, Barbosa SP, Imamura M, Battistella LR, Simis M, et al. Neuroplasticity changes in knee osteoarthritis (KOA) indexed by event-related desynchronization/synchronization during a motor inhibition task. Somatosens Mot Res 2024; 41: 149. DOI: https://doi.org/10.1080/08990220.2023.2188926
Gonçalves FT, Marques LM, Pessotto AV, Barbosa SP, Imamura M, Simis M, et al. OPRM1 and BDNF polymorphisms associated with a compensatory neurophysiologic signature in knee osteoarthritis patients. Neurophysiol Clin 2023; 53: 102917. DOI: https://doi.org/10.1016/j.neucli.2023.102917
Ingber DE. Cellular mechanotransduction: putting all the pieces together again. FASEB J 2006; 20: 811. DOI: https://doi.org/10.1096/fj.05-5424rev
d’Agostino M, Craig K, Tibalt E, Respizzi S. Shock wave as biological therapeutic tool: from mechanical stimulation to recovery and healing, through mechanotransduction. Int J Surg 2015; 24: 147. DOI: https://doi.org/10.1016/j.ijsu.2015.11.030
Hatanaka K, Ito K, Shindo T, Kagaya Y, Ogata T, Eguchi K, et al. Molecular mechanisms of the angiogenic effects of low-energy shock wave therapy: roles of mechanotransduction. Am J Physiol Cell Physiol 2016; 311: C378. DOI: https://doi.org/10.1152/ajpcell.00152.2016
Chighizola M, Dini T, Lenardi C, Milani P, Podestà A, Schulte C. Mechanotransduction in neuronal cell development and functioning. Biophys Rev 2019; 11: 701. DOI: https://doi.org/10.1007/s12551-019-00587-2
Chen KH, Qiu Z. Sensational astrocytes: mechanotransduction in adult brain function. Neuron 2022; 110: 2891. DOI: https://doi.org/10.1016/j.neuron.2022.08.007
Falleroni F, Bocchero U, Mortal S, Li Y, Ye Z, Cojoc D, et al. Mechanotransduction in hippocampal neurons operates under localized low picoNewton forces. iScience 2022; 25: 103807. DOI: https://doi.org/10.1016/j.isci.2022.103807
Lohse-Busch H, Reime U, Falland R. Symptomatic treatment of unresponsive wakefulness syndrome with transcranially focused extracorporeal shock waves. NeuroRehabilitation 2014; 35: 235. DOI: https://doi.org/10.3233/NRE-141115
Ciampa AR, Prati AC, Amelio E, Cavalieri E, Persichini T, Colasanti M, et al. Nitric oxide mediates anti-inflammatory action of extracorporeal shock waves. FEBS Lett 2005; 579: 6839. DOI: https://doi.org/10.1016/j.febslet.2005.11.023
Mariotto S, Cavalieri E, Amelio E, Ciampa AR, Prati AC, Marlinghaus E, et al. Extracorporeal shock waves: from lithotripsy to anti-inflammatory action by NO production. Nitric Oxide 2005; 12: 89. DOI: https://doi.org/10.1016/j.niox.2004.12.005
Mariotto S, Prati AC, Cavalieri E, Amelio E, Marlinghaus E, Suzuki H. Extracorporeal shock wave therapy in inflammatory diseases: molecular mechanism that triggers anti-inflammatory action. Curr Med Chem 2009; 16: 2366. DOI: https://doi.org/10.2174/092986709788682119
Knobloch K. The brain lymphatic system in Alzheimer’s disease. In: Knobloch K, Nedělka T. ESWT in neurology. Heilbronn: LEVEL10; 2022. p. 300–309.
Kylkilahti TM, Berends E, Ramos M, Shanbhag NC, Töger J, Markenroth Bloch K, et al. Achieving brain clearance and preventing neurodegenerative diseases: a glymphatic perspective. J Cereb Blood Flow Metab 2021; 41: 2137. DOI: https://doi.org/10.1177/0271678X20982388
Da Mesquita S, Papadopoulos Z, Dykstra T, Brase L, Farias FG, Wall M, et al. Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy. Nature 2021; 593: 255. DOI: https://doi.org/10.1038/s41586-021-03489-0
Zhang J, Kang N, Yu X, Ma Y, Pang X. Radial extracorporeal shock wave therapy enhances the proliferation and differentiation of neural stem cells by notch, PI3K/AKT, and Wnt/β-catenin signaling. Sci Rep 2017; 7: 15321. DOI: https://doi.org/10.1038/s41598-017-15662-5
Wojtecki L, Trenado C, Cont C, Zimmermann KM, Stute N, Schnitzler A. The great reset: transcranial pulse stimulation reduces global EEG-entropy in Alzheimer’s disease. Brain Stimulation 2021; 14: 1676. DOI: https://doi.org/10.1016/j.brs.2021.10.279
Wojtecki L, Cont C, Stute N, Galli A, Schulte C, Trenado C. Electrical brain networks before and after transcranial pulsed shockwave stimulation in Alzheimer’s patients. Geroscience 2025; 47: 953. DOI: https://doi.org/10.1007/s11357-024-01305-x
Matt E, Radjenovic S, Mitterwallner M, Beisteiner R. Current state of clinical ultrasound neuromodulation. Front Neurosci 2024; 18: 1420255. DOI: https://doi.org/10.3389/fnins.2024.1420255
Wang B, Ning H, Reed-Maldonado AB, Zhou J, Ruan Y, Zhou T, et al. Low-intensity extracorporeal shock wave therapy enhances brain-derived neurotrophic factor expression through PERK/ATF4 signaling pathway. Int J Mol Sci 2017; 18: 433. DOI: https://doi.org/10.3390/ijms18020433
Matt E, Kaindl L, Tenk S, Egger A, Kolarova T, Karahasanović N, et al. First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain. J Transl Med 2022; 20: 26. DOI: https://doi.org/10.1186/s12967-021-03222-5
Lohse-Busch H. Transcranial pulse stimulation (TPS) with focused extracorporeal shock waves: a new promising non invasive symptomatic treatment of Parkinson’s disease: casuistics and feasibility study. Preprint August 2021.
Osou S, Radjenovic S, Bender L, Gaal M, Zettl A, Dörl G, et al. Novel ultrasound neuromodulation therapy with transcranial pulse stimulation (TPS) in Parkinson’s disease: a first retrospective analysis. J Neurol 2024; 271: 1462. DOI: https://doi.org/10.1007/s00415-023-12114-1
Cheung T, Li TMH, Lam JYT, Fong KH, Chiu LY, Ho YS, et al. Effects of transcranial pulse stimulation on autism spectrum disorder: a double-blind, randomized, sham-controlled trial. Brain Commun 2023; 5: fcad226. DOI: https://doi.org/10.1093/braincomms/fcad226
Cheung T, Yee BK, Chau B, Lam JYT, Fong KH, Lo H, et al. Efficacy and safety of transcranial pulse stimulation in young adolescents with attention-deficit/hyperactivity disorder: a pilot, randomized, double-blind, sham-controlled trial. Front Neurol 2024; 15: 1364270. DOI: https://doi.org/10.3389/fneur.2024.1364270
Truong DQ, Thomas C, Hampstead BM, Datta A. Comparison of transcranial focused ultrasound and transcranial pulse stimulation for neuromodulation: a computational study. Neuromodulation 2022; 25: 606. DOI: https://doi.org/10.1016/j.neurom.2021.12.012
Slezak C, Flatscher J, Slezak P. A comparative feasibility study for transcranial extracorporeal shock wave therapy. Biomedicines 2022; 10: 1457. DOI: https://doi.org/10.3390/biomedicines10061457
Lodewyk K, Bagnell A, MacMaster FP, Newton AS. Adverse event monitoring and reporting in pediatric neuromodulatory studies: a systematic review. J Psychiatr Res 2024; 175: 359. DOI: https://doi.org/10.1016/j.jpsychires.2024.05.035
Radjenovic S, Dörl G, Gaal M, Beisteiner R. Safety of clinical ultrasound neuromodulation. Brain Sci 2022; 12: 1277. DOI: https://doi.org/10.3390/brainsci12101277
Transcranial Pulse Stimulation (TPS). Key Findings from the 2024 Survey on Transcranial Pulse Stimulation (TPS) (Internet). Tägerwilen: Storz Medical/TPS (cited 2024 Aug 9). Available from: https://www.tps-neuro.com/en/blog/2024-survey-on-transcranial-pulse-stimulation-tps
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Copyright (c) 2025 Marta Imamura, Gilson Tanaka Shinzato, Leandro Heidy Yoshioka, Sabrina Saemy Tome Uchiyama, Beatriz Akemi Tanaka, Lucas Ramos De Pretto, Felipe Fregni, Linamara Rizzo Battistella

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