The Prophylactic Effect of Acupuncture for Migraine Without Aura: A Randomized, Sham-Controlled, Clinical Trial

Abstract

Objective: Acupuncture is recognized as an effective migraine treatment, but the comparative long-term efficacy of different acupuncture methods at identical acupoints remains unclear. This study investigates the prophylactic effects of manual acupuncture (manual penetrating acupuncture, MPA) versus sham acupuncture (non-penetrating acupuncture, NPA) at the same acupoints.

Methods: In this multicenter, single-blind randomized controlled trial conducted across four Chinese clinical centers (May 2020 to September 2022), 192 migraineurs without aura (International Classification of Headache Disorders 3rd edition criteria) were randomized 1:1 to 12 sessions of MPA or NPA. Primary outcome was the change from baseline in migraine attack frequency at week 16; secondary outcomes included migraine attack frequency, responder rates, migraine days, and pain intensity (every 4 weeks), etc. Trial registration: No. ChiCTR2000032308.

Results: A total of 198 participants were randomly allocated to either MPA or NPA groups, 99 in each group. At 16 weeks, the change in MPA showed a greater reduction in migraine attacks versus NPA (mean difference [MD] = –0.6, 95% confidence interval [CI] –1.5 to 0.05; p = 0.069). MPA demonstrated superior responder rates (risk difference = 17.2%, 95% CI 5.2 to 29.1; p = 0.007) and pain reduction (MD = –0.6, 95% CI –1.1 to –0.2; p = 0.003) after treatment. At follow-up, MPA improved all migraine symptoms and some quality of life compared with NPA. Adverse events occurred in 5.1% of MPA participants.

Conclusions: Although MPA and NPA showed comparable preventive effects, MPA provided sustained symptom relief and quality-of-life improvements. Therefore, suitable acupoint selection establishes therapeutic potential, whereas acupuncture methods critically determine long-term clinical benefits.

Keywords

manual penetrating acupuncture / migraine without aura / non-penetrating acupuncture / randomized controlled trial

References

[1] D. W. Dodick, “Migraine,” Lancet 391, no. 10127 (2018): 1315-1330.

[2] M. S. Robbins, “Diagnosis and Management of Headache: A Review,” Jama 325, no. 18 (2021): 1874-1885.

[3] GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, Regional, and National Incidence, Prevalence, and Years Lived With Disability for 328 Diseases and Injuries for 195 Countries, 1990-2016: A Systematic Analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390(10100): 1211-1259.

[4] M. Ashina, Z. Katsarava, T. P. Do, et al., “Migraine: Epidemiology and Systems of Care,” Lancet 397, no. 10283 (2021): 1485-1495.

[5] E. Loder and P. Rizzoli, “Pharmacologic Prevention of Migraine: A Narrative Review of the State of the Art in 2018,” Headache 58, no. 3 (2018): 218-229.

[6] T. J. Schwedt, “Chronic Migraine,” Bmj 348 (2014): g1416.

[7] P. K. Chen and S. J. Wang, “Medication Overuse and Medication Overuse Headache: Risk Factors, Comorbidities, Associated Burdens and Nonpharmacologic and Pharmacologic Treatment Approaches,” Current Pain and Headache Reports 23, no. 8 (2019): 60.

[8] K. Linde, G. Allais, B. Brinkhaus, et al., “Acupuncture for the Prevention of Episodic Migraine,” Cochrane Database of Systematic Reviews (Online) 2016, no. 6 (2016): Cd001218.

[9] S. Xu, L. Yu, X. Luo, et al., “Manual Acupuncture Versus Sham Acupuncture and Usual Care for Prophylaxis of Episodic Migraine Without Aura: Multicentre, Randomised Clinical Trial,” Bmj 368 (2020): m697.

[10] L. Zhao, J. Chen, Y. Li, et al., “The Long-Term Effect of Acupuncture for Migraine Prophylaxis: A Randomized Clinical Trial,” JAMA Internal Medicine 177, no. 4 (2017): 508-515.

[11] Y. T. Fei, H. J. Cao, R. Y. Xia, et al., “Methodological Challenges in Design and Conduct of Randomised Controlled Trials in Acupuncture,” Bmj 376 (2022): e064345.

[12] B. Coste, “The Nobel Prize in Physiology or Medicine 2021: Temperature and Touch Sensors,” Medecine Sciences 38, no. 1 (2022): 96-98.

[13] World Medical Association. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. Jama 310, no. 20 (2013): 2191-2194.

[14] H. Macpherson, D. G. Altman, R. Hammerschlag, et al., “Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): Extending the CONSORT Statement,” Plos Medicine 7, no. 6 (2010): e1000261.

[15] Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd Edition. Cephalalgia 38, no. 1 (2018): 1-211.

[16] H. C. Diener, C. Tassorelli, D. W. Dodick, et al., “Guidelines of the International Headache Society for Controlled Trials of Preventive Treatment of Migraine Attacks in Episodic Migraine in Adults,” Cephalalgia 40, no. 10 (2020): 1026-1044.

[17] J. Chen, S. Zhou, M. Sun, et al., “Manual Acupuncture as Prophylaxis for Migraine Without Aura: Study Protocol for a Multi-Center, Randomized, Single-Blinded Trial,” Trials 23, no. 1 (2022): 574.

[18] W. Kou, I. Gareus, J. D. Bell, et al., “Quantification of DeQi Sensation by Visual Analog Scales in Healthy Humans After Immunostimulating Acupuncture Treatment,” American Journal of Chinese Medicine 35, no. 5 (2007): 753-765.

[19] National Clinical Guideline Centre. National Institute for Health and Clinical Excellence: Guidance. Headaches: Diagnosis and Management of Headaches in Young People and Adults (Royal College of Physicians (UK), 2012), https://www.ncbi.nlm.nih.gov/books/NBK327506/.

[20] R. H. Dworkin, D. C. Turk, K. W. Wyrwich, et al., “Interpreting the Clinical Importance of Treatment Outcomes in Chronic Pain Clinical Trials: IMMPACT Recommendations,” The Journal of Pain 9, no. 2 (2008): 105-121.

[21] R. R. Coeytaux, J. S. Kaufman, R. Chao, J. D. Mann, and R. F. Devellis, “Four Methods of Estimating the Minimal Important Difference Score Were Compared to Establish a Clinically Significant Change in Headache Impact Test,” Journal of Clinical Epidemiology 59, no. 4 (2006): 374-380.

[22] J. C. Cole, P. Lin, and M. F. Rupnow, “Minimal Important Differences in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version,” Cephalalgia 29, no. 11 (2009): 1180-1187.

[23] Y. Li, H. Zheng, C. M. Witt, et al., “Acupuncture for Migraine Prophylaxis: A Randomized Controlled Trial,” Cmaj 184, no. 4 (2012): 401-410.

[24] J. Liu, J. Mu, Q. Liu, W. Dun, M. Zhang, and J. Tian, “Brain Structural Properties Predict Psychologically Mediated Hypoalgesia in an 8-Week Sham Acupuncture Treatment for Migraine,” Human Brain Mapping 38, no. 9 (2017): 4386-4397.

[25] J. Y. He, X. Y. Tu, Z. F. Yin, et al., “Short-Term Effects of Cupping and Scraping Therapy for Chronic Nonspecific Low-Back Pain: A Prospective, Multicenter Randomized Trial,” Journal of Integrative Medicine 22, no. 1 (2024): 39-45.

[26] X. D. Meng, H. R. Guo, Q. Y. Zhang, et al., “The Effectiveness of Cupping Therapy on Chronic Fatigue Syndrome: A Single-Blind Randomized Controlled Trial,” Complementary Therapies in Clinical Practice 40 (2020): 101210.

[27] F. Feng, S. Yu, Z. Wang, et al., “Non-Pharmacological and Pharmacological Interventions Relieve Insomnia Symptoms by Modulating a Shared Network: A Controlled Longitudinal Study,” NeuroImage: Clinical 22 (2019): 101745.

[28] I. M. Gönenç and F. Terzioğlu, “Effects of Massage and Acupressure on Relieving Labor Pain, Reducing Labor Time, and Increasing Delivery Satisfaction,” The Journal of Nursing Research 28, no. 1 (2020): e68.

[29] D. Zeng, X. Yan, H. Deng, et al., “Placebo Response Varies Between Different Types of Sham Acupuncture: A Randomized Double-Blind Trial in Neck Pain Patients,” European Journal of Pain (London, England) 26, no. 5 (2022): 1006-1020.

[30] J. Q. Fan, W. J. Lu, W. Q. Tan, et al., “Effectiveness of Acupuncture for Anxiety Among Patients With Parkinson Disease: A Randomized Clinical Trial,” JAMA Network Open 5, no. 9 (2022): e2232133.

[31] Z. M. Cao, Y. C. Chen, G. Y. Liu, et al., “Abnormalities of Thalamic Functional Connectivity in Patients With Migraine: A Resting-State fMRI Study,” Pain and Therapy 11, no. 2 (2022): 561-574.

[32] J. Liu, S. Quan, L. Zhao, et al., “Evaluation of a Clustering Approach to Define Distinct Subgroups of Patients With Migraine to Select Electroacupuncture Treatments,” Neurology 101, no. 7 (2023): e699-e709.

[33] L. Liu, T. Tian, X. Li, et al., “Revealing the Neural Mechanism Underlying the Effects of Acupuncture on Migraine: A Systematic Review,” Frontiers in Neuroscience 15 (2021): 674852.

[34] L. Zhao, J. Liu, F. Zhang, et al., “Effects of Long-Term Acupuncture Treatment on Resting-State Brain Activity in Migraine Patients: A Randomized Controlled Trial on Active Acupoints and Inactive Acupoints,” PLoS ONE 9, no. 6 (2014): e99538.

[35] M. Linde, A. Fjell, J. Carlsson, and C. Dahlöf, “Role of the Needling Per Se in Acupuncture as Prophylaxis for Menstrually Related Migraine: A Randomized Placebo-Controlled Study,” Cephalalgia 25, no. 1 (2005): 41-47.

[36] J. Kong, D. T. Fufa, A. J. Gerber, et al., “Psychophysical Outcomes From a Randomized Pilot Study of Manual, Electro, and Sham Acupuncture Treatment on Experimentally Induced Thermal Pain,” The Journal of Pain 6, no. 1 (2005): 55-64.

[37] V. Napadow, R. P. Dhond, J. Kim, et al., “Brain Encoding of Acupuncture Sensation-Coupling On-Line Rating With fMRI,” Neuroimage 47, no. 3 (2009): 1055-1065.

[38] K. Linde, A. Streng, S. Jürgens, et al., “Acupuncture for Patients With Migraine: A Randomized Controlled Trial,” Jama 293, no. 17 (2005): 2118-2125.

[39] H. C. Diener, K. Kronfeld, G. Boewing, et al., “Efficacy of Acupuncture for the Prophylaxis of Migraine: A Multicentre Randomised Controlled Clinical Trial,” Lancet Neurology 5, no. 4 (2006): 310-316.

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