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Expert consensus on the use of botulinum toxin type A for the treatment of chronic migraine
Yangtze River Delta Smart Headache Management Committee, Neurotoxin Branch of the Chinese Society of Neuroscience
Journal of Neurology and Neurorehabilitation ›› 2026, Vol. 22 ›› Issue (2) : 77-89.
PDF(1511 KB)
PDF(1511 KB)
Expert consensus on the use of botulinum toxin type A for the treatment of chronic migraine
Migraine, with its high prevalence, ranks as the second leading cause of disability among neurological disorders. Chronic migraine, in particular, imposes a greater disease burden, leads to poorer quality of life for patients, and results in higher healthcare resource consumption. Current conventional oral preventive medications often suffer from inadequate efficacy, poor tolerability, and potential drug-drug interactions, which can contribute to the persistence of headaches. This makes chronic migraine a significant clinical challenge and public health issue. Botulinum toxin type A injection has gained widespread attention as an effective preventive treatment for chronic migraine. This expert consensus is developed based on domestic and international advances in diagnosis and treatment, combined with the actual situation in China, with the aim of guiding neurologists and other relevant clinicians in the standardized use of botulinum toxin type A for the management of chronic migraine.
Chronic migraine / Botulinum toxin type A / Treatment / Expert consensus
| [1] | STEINER T J, STOVNER L J. Global epidemiology of migraine and its implications for public health and health policy[J]. Nat Rev Neurol, 2023, 19(2):109-117. |
| [2] | FRAMPTON J E, SILBERSTEIN S. OnabotulinumtoxinA: A review in the prevention of chronic migraine[J]. Drugs, 2018, 78(5):589-600. |
| [3] | DIENER H C, DODICK D W, AURORA S K, et al. OnabotulinumtoxinA for treatment of chronic migraine: Results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial[J]. Cephalalgia, 2010, 30(7):804-814. |
| [4] | DIENER H C, DODICK D W, AURORA S K, et al. OnabotulinumtoxinA for treatment of chronic migraine: Results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial[J]. Cephalalgia, 2010, 30(7):804-814. |
| [5] | STEINER T J, STOVNER L J, JENSEN R, et al. Migraine remains second among the world's causes of disability, and first among young women: Findings from GBD2019[J/OL]. J Headache Pain, 2020, 21:137[2025-11-25]. . |
| [6] | NATOLI J L, MANACK A, DEAN B, et al. Global prevalence of chronic migraine: A systematic review[J]. Cephalalgia, 2010, 30(5):599-609. |
| [7] | MAY A, SCHULTE L H. Chronic migraine: Risk factors, mechanisms and treatment[J]. Nat Rev Neurol, 2016,12(8):455-464. |
| [8] | BIGAL M E, LIPTON R B. Concepts and mechanisms of migraine chronification[J]. Headache, 2008, 48(1):7-15. |
| [9] | Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition[J]. Cephalalgia, 2018, 38(1):1-211. |
| [10] | VOELKER R. What is chronic migraine?[J/OL]. Jama, 2025, 333(24):2216[2025-11-25]. . |
| [11] | OLIVEIRA R, GIL-GOUVEIA R, PULEDDA F. CGRP-targeted medication in chronic migraine-systematic review[J/OL]. J Headache Pain, 2024, 25(1):51[2025-11-25]. . |
| [12] | BIGAL M E, LIPTON R B. What predicts the change from episodic to chronic migraine?[J]. Curr Opin Neurol, 2009, 22(3):269-276. |
| [13] | CHOU T M, CHEN S P. Animal models of chronic migraine[J/OL]. Curr Pain Headache Rep, 2018, 22(6):44. . |
| [14] | SU M, YU S. Chronic migraine: A process of dysmodulation and sensitization[J/OL]. Mol Pain, 2018, 14:1744806918767697[2025-11-25]. . |
| [15] | EDVINSSON L, HAANES K A, WARFVINGE K. Does inflammation have a role in migraine?[J]. Nat Rev Neurol, 2019, 15(8):483-490. |
| [16] | GONG J, DUAN X, XIANG B, et al. Transcriptomic changes in the hypothalamus of mice with chronic migraine: Activation of pathways associated with neuropathic inflammation and central sensitization[J/OL]. Mol Cell Neurosci, 2024,131:103968[2025-11-25]. . |
| [17] | LIU Q, YAN R, WANG L, et al. Alpha-asarone alleviates cutaneous hyperalgesia by inhibiting hyperexcitability and neurogenic inflammation via TLR4/NF-κB/NLRP3 signaling pathway in a female chronic migraine rat model[J/OL]. Neuropharmacology, 2024, 261:110158[2025-11-25]. . |
| [18] | WEN Q, WANG Y, PAN Q, et al. MicroRNA-155-5p promotes neuroinflammation and central sensitization via inhibiting SIRT1 in a nitroglycerin-induced chronic migraine mouse model[J/OL]. J Neuroinflammation, 2021, 18(1):287[2025-11-25]. . |
| [19] | NELSON-MANEY N P, BáLINT L, BEESON A L, et al. Meningeal lymphatic CGRP signaling governs pain via cerebrospinal fluid efflux and neuroinflammation in migraine models[J/OL]. J Clin Invest, 2024, 134(15):e175616[2025-11-25]. . |
| [20] | IMIG C, MIN S W, KRINNER S, et al. The morphological and molecular nature of synaptic vesicle priming at presynaptic active zones[J]. Neuron, 2014, 84(2):416-431. |
| [21] | ROSSETTO O, PIRAZZINI M, MONTECUCCO C. Botulinum neurotoxins: Genetic, structural and mechanistic insights[J]. Nat Rev Microbiol, 2014, 12(8):535-549. |
| [22] | SUDHOF TC, RIZO J. Synaptic vesicle exocytosis[J/OL]. Cold Spring Harb Perspect Biol, 2011, 3(12):a005637[2025-11-25]. . |
| [23] | POZO-ROSICH P, ALPUENTE A, SILBERSTEIN S D, et al. Insights from 25?years of onabotulinumtoxinA in migraine-mechanisms and management[J]. Nat Rev Neurol, 2024, 20(9):555-568. |
| [24] | DE LA TORRE CANALES G, POLUHA R L, BONJARDIM L R, et al. Botulinum toxin-a effects on pain, somatosensory and psychosocial features of patients with refractory masticatory myofascial pain: A randomized double-blind clinical trial[J/OL]. Sci Rep, 2024, 14:4201[2025-11-25]. . |
| [25] | MATAK I, B?LCSKEI K, BACH-ROJECKY L, et al. Mechanisms of botulinum toxin type a action on pain[J/OL]. Toxins, 2019, 11(8):459[2025-11-25]. . |
| [26] | ZHANG X, STRASSMAN A M, NOVACK V, et al. Extracranial injections of botulinum neurotoxin type A inhibit intracranial meningeal nociceptors' responses to stimulation of TRPV1 and TRPA1 channels: Are we getting closer to solving this puzzle?[J]. Cephalalgia, 2016, 36(9):875-886. |
| [27] | MELO-CARRILLO A, STRASSMAN A M, SCHAIN A J, et al. Exploring the effects of extracranial injections of botulinum toxin type A on prolonged intracranial meningeal nociceptors responses to cortical spreading depression in female rats[J]. Cephalalgia, 2019, 39(11):1358-1365. |
| [28] | MELO-CARRILLO A, STRASSMAN A M, SCHAIN A J, et al. OnabotulinumtoxinA affects cortical recovery period but not occurrence or propagation of cortical spreading depression in rats with compromised blood-brain barrier[J]. Pain, 2021, 162(9):2418-2427. |
| [29] | DODICK D W, TURKEL C C, DEGRYSE R E, et al. OnabotulinumtoxinA for treatment of chronic migraine: Pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program[J]. Headache, 2010, 50(6):921-936. |
| [30] | BENDTSEN L, SACCO S, ASHINA M, et al. Guideline on the use of onabotulinumtoxinA in chronic migraine: A consensus statement from the European Headache Federation[J/OL]. J Headache Pain, 2018, 19(1):91[2025-11-25]. . |
| [31] | MARTINELLI D, ARCERI S, DE ICCO R, et al. BoNT-A efficacy in high frequency migraine: An open label, single arm, exploratory study applying the PREEMPT paradigm[J]. Cephalalgia, 2022, 42(2):170-175. |
| [32] | ALPUENTE A, GALLARDO V J, TORRES-FERRUS M, et al. Early efficacy and late gain in chronic and high-frequency episodic migraine with onabotulinumtoxinA[J]. Eur J Neurol, 2019, 26(12):1464-1470. |
| [33] | SACCO S, BRASCHINSKY M, DUCROS A, et al. European headache federation consensus on the definition of resistant and refractory migraine: Developed with the endorsement of the European Migraine & Headache Alliance (EMHA)[J/OL]. J Headache Pain, 2020, 21(1):76[2025-11-25]. . |
| [34] | ORNELLO R, ANDREOU A P, DE MATTEIS E, et al. Resistant and refractory migraine: Clinical presentation, pathophysiology, and management[J/OL]. eBioMedicine, 2024, 99:104943[2025-11-25]. . |
| [35] | AHMED F, ZAFAR H W, BUTURE A, et al. Does analgesic overuse matter? Response to OnabotulinumtoxinA in patients with chronic migraine with or without medication overuse[J/OL]. Springerplus, 2015, 4:589[2025-11-25]. . |
| [36] | GUERZONI S, PELLESI L, BARALDI C, et al. Long-term treatment benefits and prolonged efficacy of OnabotulinumtoxinA in patients affected by chronic migraine and medication overuse headache over 3?Years of therapy[J/OL]. Front Neurol, 2017, 8:586[2025-11-25]. . |
| [37] | NEGRO A, CURTO M, LIONETTO L, et al. OnabotulinumtoxinA 155 U in medication overuse headache: A two years prospective study[J/OL]. Springerplus, 2015, 4:826[2025-11-25]. . |
| [38] | CARONNA E, GALLARDO V J, HERNáNDEZ-BELTRáN N, et al. OnabotulinumtoxinA: An effective tool in the therapeutic arsenal for chronic migraine with medication overuse[J/OL]. Front Neurol, 2018, 9:808[2025-11-25]. . |
| [39] | LANG H, PENG C, WU K, et al. Efficacy and safety of onabotulinumtoxinA in the treatment of medication overuse headache: A systematic review[J/OL]. Front Neurol, 2024, 15:1453183[2025-11-25]. . |
| [40] | PIJPERS J A, KIES D A, LOUTER M A, et al. Acute withdrawal and botulinum toxin A in chronic migraine with medication overuse: A double-blind randomized controlled trial[J]. Brain, 2019, 142(5):1203-1214. |
| [41] | AHMED F, GAUL C, KOLLEWE K, et al. Real-world safety and efficacy of 156 U - 195 U OnabotulinumtoxinA in adults with chronic migraine: Results from the REPOSE study[J/OL]. BMC Neurol, 2025, 25(1):197[2025-11-25]. . |
| [42] | DIENER H C, DODICK D W, TURKEL C C, et al. Pooled analysis of the safety and tolerability of onabotulinumtoxinA in the treatment of chronic migraine[J]. Eur J Neurol, 2014, 21(6):851-859. |
| [43] | ?Z?N A ?. Does the efficacy of different doses of Botulinum neurotoxin in chronic migraine change in terms of age and sex?[J]. Gulhane Med J, 2020, 62(1):51-56. |
| [44] | MAVRIDI A, REDMOND A, ARCHONTAKIS-BARAKAKIS P, et al. Onabotulinumtoxina in the prevention of migraine in pediatric population: A systematic review[J/OL]. Toxins, 2024, 16(7):295[2025-11-25]. . |
| [45] | ROBINSON A Y, GROGAN P M. OnabotulinumtoxinA successfully used as migraine prophylaxis during pregnancy: A case report[J/OL]. Mil Med, 2014, 179(6):e703-e704[2025-11-25]. . |
| [46] | WONG H T, KHAN R, BUTURE A, et al. OnabotulinumtoxinA treatment for chronic migraine in pregnancy: An updated report of real-world headache and pregnancy outcomes over 14 years in Hull[J/OL]. Cephalalgia, 2025, 45(5):0333102425132 7387[2025-11-25]. . |
| [47] | MATHARU M, PASCUAL J, NILSSON REMAHL I, et al. Utilization and safety of onabotulinumtoxinA for the prophylactic treatment of chronic migraine from an observational study in Europe[J]. Cephalalgia, 2017, 37(14):1384-1397. |
| [48] | KHAN F A, MOHAMMED A E, POONGKUNRAN M, et al. Wearing off effect of OnabotulinumtoxinA near the end of treatment cycle for chronic migraine: A 4-year clinical experience[J]. Headache, 2020, 60(2):430-440. |
| [49] | RUSCHEWEYH R, ATHWAL B, GRYGLAS-DWORAK A, et al. Wear-off of OnabotulinumtoxinA effect over the treatment interval in chronic migraine: A retrospective chart review with analysis of headache diaries[J]. Headache, 2020, 60(8):1673-1682. |
| [50] | STOVNER L J, HAGEN K, TRONVIK E, et al. FollowTheSutures: Piloting a new way to administer OnabotulinumtoxinA for chronic migraine[J]. Cephalalgia, 2022, 42(7):590-597. |
| [51] | BONO F, MAZZA M R, MAGRO G, et al. Regional targeted subcutaneous injection of botulinum neurotoxin type A in refractory chronic migraine: A randomized, double-blind, placebo-controlled study[J/OL]. Toxins, 2023, 15(5):324[2025-11-25]. . |
| [52] | SANTORO A, FONTANA A, COPETTI M, et al. Real-world insights into the effectiveness and tolerability of OnabotulinumtoxinA in chronic migraine: A long-term evaluation of up to 11 years[J/OL]. Toxins, 2025, 17(4):208[2025-11-25]. . |
| [53] | PULEDDA F, SACCO S, DIENER H C, et al. International headache society global practice recommendations for preventive pharmacological treatment of migraine[J]. Cephalalgia, 2024, 44(9):3331024241269 735[2025-11-25]. . |
| [54] | PELLESI L, GARCIA-AZORIN D, RUBIO-BELTRáN E, et al. Combining treatments for migraine prophylaxis: The state-of-the-art[J/OL]. J Headache Pain, 2024, 25(1):214[2025-11-25]. . |
| [55] | SCUTERI D, LAWRENCE G W, IANNACCHERO R, et al. Efficacy and safety of mAbs anti-CGRP/CGRP R (eptinezumab and erenumab) or atogepant in combination with OnabotulinumtoxinA in refractory chronic migraine: A clinical trial protocol[J]. Pain Manag, 2025, 15(4):177-181. |
| [56] | DOMíNGUEZ C, POZO-ROSICH P, TORRES-FERRúS M, et al. OnabotulinumtoxinA in chronic migraine: Predictors of response. A prospective multicentre descriptive study[J]. Eur J Neurol, 2018, 25(2):411-416. |
| [57] | ALPUENTE A, GALLARDO V J, TORRES-FERRúS M, et al. Short and mid-term predictors of response to OnabotulinumtoxinA: Real-life experience observational study[J]. Headache, 2020, 60(4):677-685. |
| [58] | VIUDEZ-MARTíNEZ A, TORREGROSA A B, NAVARRETE F, et al. Understanding the biological relationship between migraine and depression[J/OL]. Biomolecules, 2024, 14(2):163[2025-11-25]. . |
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