Abstract
Purpose of Review
To summarize the clinical neuroimaging evidence pertaining to the potential mechanisms of acupuncture for migraine prophylaxis.
Recent Findings
From a descriptive perspective, converging evidence from recent neuroimaging studies, mainly from functional MRI (fMRI) studies, has demonstrated that when compared with sham acupuncture, verum acupuncture could normalize the decrease of the functional connectivity of the rostral ventromedial medulla-trigeminocervical complex (RVM/TCC) network, frontal-parietal network, cingulo-opercular networks, and default mode network and could normalize sensorimotor network connectivity with sensory-, affective-, and cognitive-related brain areas. These areas overlap with those of the pain matrix. Verum acupuncture works in a more targeted and unique manner compared with sham acupuncture in patients with migraine.
Summary
These findings from neuroimaging studies may provide new perspectives on the validation of acupoints specificity and confirm the central modulating effects of acupuncture as a migraine prevention treatment. However, the exact mechanism by which acupuncture works for migraine prophylaxis remains unclear and warrants investigation. Future studies with larger sample sizes are still needed to confirm the current results and to further evaluate the complex and specific effects of acupuncture by analyzing different stimulus conditions, such as verum vs. sham acupuncture, deqi vs. no deqi, different acupuncture points or meridians, and different manipulation methods. Moreover, instead of focusing on the changes in a single area of the brain, researchers should focus more on the relationships among the functional connectivity network of brain areas such as the RVM/TCC, thalamus, anterior cingulate cortex (ACC), superior temporal gyrus (STG), and supplementary motor area (SMA) to explore the underlying mechanism of the effects of acupuncture.
Similar content being viewed by others
References
Patel NV, Bigal ME, Kolodner KB, Leotta C, Lafata JE, Lipton RB. Prevalence and impact of migraine and probable migraine in a health plan. Neurology. 2004;63(8):1432–8.
Lipton RB, Scher AI, Kolodner K, Liberman J, Steiner TJ, Stewart WF. Migraine in the United States: epidemiology and patterns of health care use. Neurology. 2002;58(6):885–94.
Stovner LJ, Zwart JA, Hagen K, Terwindt GM, Pascual J. Epidemiology of headache in Europe. Eur J Neurol. 2006;13(4):333–45.
Steiner TJ, Scher AI, Stewart WF, Kolodner K, Liberman J, Lipton RB. The prevalence and disability burden of adult migraine in England and their relationships to age, gender and ethnicity. Cephalalgia. 2003;23(7):519–27.
Sakai F, Igarashi H. Prevalence of migraine in Japan: a nationwide survey. Cephalalgia. 1997;17(1):15–22.
Cheung RT. Prevalence of migraine, tension-type headache, and other headaches in Hong Kong. Headache. 2000;40(6):473–9.
Hepp Z, Bloudek LM, Varon SF. Systematic review of migraine prophylaxis adherence and persistence. J Manag Care Pharm. 2014;20(1):22–33.
Wang SJ, Fuh JL, Young YH, Lu SR, Shia BC. Prevalence of migraine in Taipei, Taiwan: a population-based survey. Cephalalgia. 2000;20(6):566–72.
Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41(7):646–57.
Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343–9.
Stovner L, Hagen K, Jensen R, Katsarava Z, Lipton R, Scher A, et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia. 2007;27(3):193–210.
Menken M, Munsat TL, Toole JF. The global burden of disease study: implications for neurology. Arch Neurol. 2000;57(3):418–20.
Pringsheim T, Davenport W, Mackie G, Worthington I, Aube M, Christie SN, et al. Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci. 2012;39(2 Suppl 2):S1–59.
Linde K, Allais G, Brinkhaus B, Fei Y, Mehring M, Vertosick EA, Vickers A, White AR. Acupuncture for the prevention of episodic migraine. Cochrane Database Syst Rev. 2016 Jun 28;2016(6):CD001218. https://doi.org/10.1002/14651858.CD001218.pub3. PMID: 27351677; PMCID: PMC4977344..
Linde K, Allais G, Brinkhaus B, Manheimer E, Vickers A, White AR. Acupuncture for migraine prophylaxis. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD001218. https://doi.org/10.1002/14651858.CD001218.pub2. Update in: Cochrane Database Syst Rev. 2016;(6):CD001218. PMID: 19160193; PMCID: PMC3099267.
Li Z, Zeng F, Yin T, Lan L, Makris N, Jorgenson K, et al. Acupuncture modulates the abnormal brainstem activity in migraine without aura patients. Neuroimage Clin. 2017;15:367–75.
Zhao L, Liu J, Zhang F, Dong X, Peng Y, Qin W, 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. 2014;9(6):e99538.
Tu Y, Zeng F, Lan L, Li Z, Maleki N, Liu B, et al. An fMRI-based neural marker for migraine without aura. Neurology. 2020;94(7):e741–51.
Li K, Zhang Y, Ning Y, Zhang H, Liu H, Fu C, et al. The effects of acupuncture treatment on the right frontoparietal network in migraine without aura patients. J Headache Pain. 2015;16:518.
Zhang Y, Li KS, Liu HW, Fu CH, Chen S, Tan ZJ, et al. Acupuncture treatment modulates the resting-state functional connectivity of brain regions in migraine patients without aura. Chin J Integr Med. 2016;22(4):293–301.
Cai RL, Shen GM, Wang H, Guan YY. Brain functional connectivity network studies of acupuncture: a systematic review on resting-state fMRI. J Integr Med. 2018;16(1):26–33.
Sutherland HG, Albury CL, Griffiths LR. Advances in genetics of migraine. J Headache Pain. 2019;20(1):72.
Schulte LH, Allers A, May A. Hypothalamus as a mediator of chronic migraine: evidence from high-resolution fMRI. Neurology. 2017;88(21):2011–6.
Schulte LH, May A. The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain. 2016;139(Pt 7):1987–93.
Kramer DR, Fujii T, Ohiorhenuan I, Liu CY. Cortical spreading depolarization: pathophysiology, implications, and future directions. J Clin Neurosci. 2016;24:22–7.
Di Lorenzo C, Grieco GS, Santorelli FM. Migraine headache: a review of the molecular genetics of a common disorder. J Headache Pain. 2012;13(7):571–80.
Noseda R, Jakubowski M, Kainz V, Borsook D, Burstein R. Cortical projections of functionally identified thalamic trigeminovascular neurons: implications for migraine headache and its associated symptoms. J Neurosci. 2011;31(40):14204–17.
Dodick DW. Migraine. Lancet. 2018;391(10127):1315–30.
Charbit AR, Akerman S, Holland PR, Goadsby PJ. Neurons of the dopaminergic/calcitonin gene-related peptide A11 cell group modulate neuronal firing in the trigeminocervical complex: an electrophysiological and immunohistochemical study. J Neurosci. 2009;29(40):12532–41.
Fields HL, Malick A, Burstein R. Dorsal horn projection targets of ON and OFF cells in the rostral ventromedial medulla. J Neurophysiol. 1995;74(4):1742–59.
Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97(2):553–622.
Holden JE, Naleway E. Microinjection of carbachol in the lateral hypothalamus produces opposing actions on nociception mediated by alpha(1)- and alpha(2)-adrenoceptors. Brain Res. 2001;911(1):27–36.
Haanes KA, Edvinsson L. Pathophysiological mechanisms in migraine and the identification of new therapeutic targets. CNS Drugs. 2019;33(6):525–37.
Dimond EG. Acupuncture anesthesia. Western medicine and Chinese traditional medicine. JAMA. 1971;218(10):1558–63.
Zhao ZQ. Neural mechanism underlying acupuncture analgesia. Prog Neurobiol. 2008 Aug;85(4):355-75. https://doi.org/10.1016/j.pneurobio.2008.05.004. Epub 2008 Jun 5. PMID: 18582529.
Zhang ZJ, Wang XM, McAlonan GM. Neural acupuncture unit: a new concept for interpreting effects and mechanisms of acupuncture. Evid Based Complement Alternat Med. 2012;2012:429412.
Huang W, Pach D, Napadow V, Park K, Long X, Neumann J, et al. Characterizing acupuncture stimuli using brain imaging with FMRI--a systematic review and meta-analysis of the literature. PLoS One. 2012;7(4):e32960.
Maleki N, Gollub RL. What have we learned from brain functional connectivity studies in migraine headache? Headache. 2016;56(3):453–61.
Chong CD, Gaw N, Fu Y, Li J, Wu T, Schwedt TJ. Migraine classification using magnetic resonance imaging resting-state functional connectivity data. Cephalalgia. 2017;37(9):828–44.
Liu CH, Kung YY, Yeh TC, Hsu PS, Yang CJ, Cheng CM, et al. Differing spontaneous brain activity in healthy adults with two different body constitutions: a resting-state functional magnetic resonance imaging study. J Clin Med. 2019;8(7).
He T, Zhu W, Du SQ, Yang JW, Li F, Yang BF, et al. Neural mechanisms of acupuncture as revealed by fMRI studies. Auton Neurosci. 2015;190:1–9.
Stankewitz A, Aderjan D, Eippert F, May A. Trigeminal nociceptive transmission in migraineurs predicts migraine attacks. J Neurosci. 2011;31(6):1937–43.
Kroger IL, May A. Triptan-induced disruption of trigemino-cortical connectivity. Neurology. 2015;84(21):2124–31.
Egorova N, Gollub RL, Kong J. Repeated verum but not placebo acupuncture normalizes connectivity in brain regions dysregulated in chronic pain. Neuroimage Clin. 2015;9:430–5.
Chen X, Spaeth RB, Freeman SG, Scarborough DM, Hashmi JA, Wey HY, et al. The modulation effect of longitudinal acupuncture on resting state functional connectivity in knee osteoarthritis patients. Mol Pain. 2015;11:67.
Han JS. Acupuncture analgesia: areas of consensus and controversy. Pain. 2011;152(3 Suppl):S41–8.
Han Y, Wang J, Zhao Z, Min B, Lu J, Li K, et al. Frequency-dependent changes in the amplitude of low-frequency fluctuations in amnestic mild cognitive impairment: a resting-state fMRI study. Neuroimage. 2011;55(1):287–95.
Kim JH, Kim S, Suh SI, Koh SB, Park KW, Oh K. Interictal metabolic changes in episodic migraine: a voxel-based FDG-PET study. Cephalalgia. 2010;30(1):53–61.
Aderjan D, Stankewitz A, May A. Neuronal mechanisms during repetitive trigemino-nociceptive stimulation in migraine patients. Pain. 2010;151(1):97–103.
Rocca MA, Ceccarelli A, Falini A, Colombo B, Tortorella P, Bernasconi L, et al. Brain gray matter changes in migraine patients with T2-visible lesions: a 3-T MRI study. Stroke. 2006;37(7):1765–70.
Jin C, Yuan K, Zhao L, Zhao L, Yu D, von Deneen KM, et al. Structural and functional abnormalities in migraine patients without aura. NMR Biomed. 2013;26(1):58–64.
Wager TD, Rilling JK, Smith EE, Sokolik A, Casey KL, Davidson RJ, et al. Placebo-induced changes in FMRI in the anticipation and experience of pain. Science. 2004;303(5661):1162–7.
Maleki N, Barmettler G, Moulton EA, Scrivani S, Veggeberg R, Spierings EL, et al. Female migraineurs show lack of insular thinning with age. Pain. 2015;156(7):1232–9.
Sun R, Yang Y, Li Z, Li Y, Cheng S, Zeng F. Connectomics: a new direction in research to understand the mechanism of acupuncture. Evid Based Complement Alternat Med. 2014;2014:568429.
Tu Y, Ortiz A, Gollub RL, Cao J, Gerber J, Lang C, et al. Multivariate resting-state functional connectivity predicts responses to real and sham acupuncture treatment in chronic low back pain. Neuroimage Clin. 2019;23:101885.
Harris RE, Zubieta JK, Scott DJ, Napadow V, Gracely RH, Clauw DJ. Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opioid receptors (MORs). Neuroimage. 2009;47(3):1077–85.
Maleki N, Becerra L, Brawn J, Bigal M, Burstein R, Borsook D. Concurrent functional and structural cortical alterations in migraine. Cephalalgia. 2012;32(8):607–20.
Mainero C, Boshyan J, Hadjikhani N. Altered functional magnetic resonance imaging resting-state connectivity in periaqueductal gray networks in migraine. Ann Neurol. 2011;70(5):838–45.
Tessitore A, Russo A, Giordano A, Conte F, Corbo D, De Stefano M, et al. Disrupted default mode network connectivity in migraine without aura. J Headache Pain. 2013;14:89.
Henry DE, Chiodo AE, Yang W. Central nervous system reorganization in a variety of chronic pain states: a review. PM R. 2011;3(12):1116–25.
Villarreal Santiago M, Tumilty S, Macznik A, Mani R. Does acupuncture alter pain-related functional connectivity of the central nervous system? A systematic review. J Acupunct Meridian Stud. 2016;9(4):167–77.
Chen X, Spaeth RB, Retzepi K, Ott D, Kong J. Acupuncture modulates cortical thickness and functional connectivity in knee osteoarthritis patients. Sci Rep. 2014;4:6482.
Li J, Zhang JH, Yi T, Tang WJ, Wang SW, Dong JC. Acupuncture treatment of chronic low back pain reverses an abnormal brain default mode network in correlation with clinical pain relief. Acupunct Med. 2014;32(2):102–8.
Maeda Y, Kettner N, Lee J, Kim J, Cina S, Malatesta C, et al. Acupuncture-evoked response in somatosensory and prefrontal cortices predicts immediate pain reduction in carpal tunnel syndrome. Evid Based Complement Alternat Med. 2013;2013:795906.
Cao J, Tu Y, Orr SP, Lang C, Park J, Vangel M, et al. Analgesic effects evoked by real and imagined acupuncture: a neuroimaging study. Cereb Cortex. 2019;29(8):3220–31.
Zhao L, Chen J, Li Y, Sun X, Chang X, Zheng H, et al. The long-term effect of acupuncture for migraine prophylaxis: a randomized clinical trial. JAMA Intern Med. 2017;177(4):508–15.
Rothschild BM. Migraines-the parable of the people who were blind and the elephant. JAMA Intern Med. 2017;177(10):1536.
Funding
This study was supported by a grant from Kuang Tien General Hospital, Taichung, Taiwan, and Taipei Veterans General Hospital, Taipei, Taiwan. This research was supported by Ministry of Science and Technology, Taiwan (MOST109-2321-B-010-006), and Brain Research Center, National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan.
Author information
Authors and Affiliations
Contributions
CMC, CPY, and SJW were responsible for the study concept, design, and review and interpretation of the data. CMC, CPY, CCY, and PHS were responsible for drafting the manuscript. SJW made modifications to the study design and revised the manuscript. CMC, CPY, and PHS contributed to the collection and analysis. CMC, CPY, and SJW contributed to the interpretation of the data and revised the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare no competing interests.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Disclaimer
The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Chronic Daily Headache
Rights and permissions
About this article
Cite this article
Chang, CM., Yang, CP., Yang, CC. et al. Evidence of Potential Mechanisms of Acupuncture from Functional MRI Data for Migraine Prophylaxis. Curr Pain Headache Rep 25, 49 (2021). https://doi.org/10.1007/s11916-021-00961-4
Accepted:
Published:
DOI: https://doi.org/10.1007/s11916-021-00961-4