肉毒毒素A治疗肌痉挛：机制、策略与精准治疗进展

doi:10.13418/j.issn.1001-165x.2026.2.17

PDF(1070 KB)

中国临床解剖学杂志 ›› 2026, Vol. 44 ›› Issue (2) : 234-238. DOI: 10.13418/j.issn.1001-165x.2026.2.17

综述

肉毒毒素A治疗肌痉挛：机制、策略与精准治疗进展

赵红波，杨胜波*

作者信息 +

Botulinum neurotoxin A in the treatment of muscle spasticity: A review of new advances in mechanism, therapeutic strategies, and precision therapy

Zhao Hongbo, Yang Shengbo*

Author information +

文章历史 +

摘要

肌痉挛常见于脑卒中、脊髓损伤等疾病，严重损害运动功能与生活质量。肉毒毒素A作为靶向性神经肌肉接头阻断剂，是治疗局灶性肌痉挛的一线方案。其经典机制为切割突触小体相关蛋白25，抑制乙酰胆碱释放。近年研究揭示，肉毒毒素A还具有多层级中枢调控作用：通过降低肌梭敏感性、恢复脊髓抑制平衡、阻断“疼痛-痉挛循环”，并驱动大脑皮层功能重组，形成系统性疗效。临床证实其可显著改善肌张力、关节活动度及疼痛。当前治疗趋于精准化，影像与电生理引导提升了注射准确性；针对神经入肌点、肌内神经密集区等新靶点的研究可实现“增效减量”；联合康复训练、冲击波等多模式方案展现出协同优势。其长期安全性尤其是对肌肉结构与免疫原性的影响仍需关注。未来需结合人工智能预测模型、新型制剂及多模态策略，推动治疗向更高层次的个体化与功能重塑发展。

Abstract

Muscle spasticity, frequently occurring after stroke or spinal cord injury, severely compromises motor function and quality of life. Botulinum neurotoxin A, a targeted neuromuscular junction blocker, serves as a first line treatment for focal spasticity. Its classic mechanism involves cleaving synaptosomal-associated protein 25, thereby inhibiting acetylcholine release. Recent research has unveiled its multi-level central modulatory effects. BoNT-A exerts systemic therapeutic benefits by reducing muscle spindle sensitivity, restoring spinal inhibitory balance, disrupting the “pain-spasm cycle,” and driving functional reorganization in the cerebral cortex. Clinically, it has proven effective in significantly improving muscle tone, range of motion, and pain. Current treatment is advancing toward greater precision. The use of imaging and electrophysiological guidance has enhanced injection accuracy. Research on novel targets, such as the nerve entry point and Intramuscular nerve dense region, aims to achieve "enhanced efficacy with reduced dosage." Furthermore, multimodal approaches combining BoNT-A with rehabilitation or extracorporeal shockwave therapy demonstrate synergistic advantages. However, long-term safety profiles, particularly concerning muscle structure and immunogenicity, require continued scrutiny. Future directions should integrate artificial intelligence-based prediction models, novel BoNT formulations, and multimodal strategies to advance treatment toward a higher standard of personalization and functional restoration.

导出引用

赵红波, 杨胜波. 肉毒毒素A治疗肌痉挛：机制、策略与精准治疗进展[J]. 中国临床解剖学杂志. 2026, 44(2): 234-238 https://doi.org/10.13418/j.issn.1001-165x.2026.2.17

Zhao Hongbo, Yang Shengbo. Botulinum neurotoxin A in the treatment of muscle spasticity: A review of new advances in mechanism, therapeutic strategies, and precision therapy[J]. Chinese Journal of Clinical Anatomy. 2026, 44(2): 234-238 https://doi.org/10.13418/j.issn.1001-165x.2026.2.17

中图分类号： R322

参考文献

[1] Wissel J, Ri S. Assessment, goal setting, and botulinum neurotoxin a therapy in the management of post-stroke spastic movement disorder: updated perspectives on best practice[J]. Expert Rev Neurother, 2022, 22(1): 27-42. DOI:10.1080/14737175.2021.2021072.
[2] Gupta AD, Baguley I, Estell J, et al. Statement of the Rehabilitation Medicine Society of Australia and New Zealand for the therapeutic use of botulinum toxin A in spasticity management[J]. Intern Med J, 2024, 54(1): 178-182. DOI:10.1111/imj.16300.
[3] Gracies JM, Esquenazi A, Brashear A, et al. Efficacy and safety of abobotulinumtoxin A in spastic lower limb: Randomized trial and extension[J]. Neurology, 2017, 89(22): 2245-2253. DOI:10.1212/WNL. 0000000000004687.
[4] Ibrahim H, Retailleau K, Hornby F, et al. A Novel Catalytically Inactive Construct of Botulinum Neurotoxin A (BoNT/A) Directly Inhibits Visceral Sensory Signalling[J]. Toxins (Basel), 2024, 16(1): 30. DOI: 10.3390/toxins16010030.
[5] Dunant Y, Gisiger V. Ultrafast and Slow Cholinergic Transmission. Different Involvement of Acetylcholinesterase Molecular Forms[J]. Molecules, 2017, 22(8): 1300. DOI:10.3390/molecules22081300.
[6] Pirazzini M, Rossetto O, Eleopra R, et al. Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology[J]. Pharmacol Rev, 2017, 69(2): 200-235. DOI:10.1124/pr.116.012658.
[7] Zhou K, Luo W, Liu T, et al. Neurotoxins Acting at Synaptic Sites: A Brief Review on Mechanisms and Clinical Applications[J]. Toxins (Basel), 2022, 15(1): 18. DOI:10.3390/toxins15010018.
[8] Weise D, Weise CM, Naumann M. Central Effects of Botulinum Neurotoxin-Evidence from Human Studies[J]. Toxins (Basel), 2019, 11(1): 21. DOI:10.3390/toxins11010021.
[9] Li S, Francisco GE, Rymer WZ. A new definition of poststroke spasticity and the interferenceof spasticity with motor recovery from acute to chronic stages[J]. Neurorehabil Neural Repair, 2021, 35(7): 601-610.
[10] Hok P, Veverka T, Hluštík P, et al. The Central Effects of Botulinum Toxin in Dystonia and Spasticity[J]. Toxins (Basel), 2021, 13(2): 155. DOI:10.3390/toxins13020155.
[11] Aslami ZV, Weitzner AS, Padovano W, et al. Evaluating mechanisms and surgical alternatives to hyperselective neurectomy for treatment of spasticity in a rat model of spinal cord injury[J]. Plast Reconstr Surg, 2025, 10: 1097. DOI:10.1097/PRS.0000000000012487.
[12] Simic J, Østlie K, Biering-Sørensen F, et al. The effect of short-term treatment with botulinum toxin a on muscle stiffness in stroke patients: an exploratory study[J]. J Rehabil Med, 2025, 57: jrm44318. DOI:10.2340/jrm.v57.44318.
[13] Costamagna D, Bastianini V, Corvelyn M, et al. Botulinum Toxin Treatment of Adult Muscle Stem Cells from Children with Cerebral Palsy and hiPSC-Derived Neuromuscular Junctions[J]. Cells, 2023, 12(16): 2072. DOI:10.3390/cells12162072.
[14]Poenaru D, Sandulescu MI, Cinteza D. Pain Modulation in Chronic Musculoskeletal Disorders: Botulinum Toxin, a Descriptive Analysis[J]. Biomedicines, 2023, 11(7): 1888. DOI:10.3390/biomedicines11071 888.
[15]Rasetti-Escargueil C, Palea S. Embracing the Versatility of Botulinum Neurotoxins in Conventional and New Therapeutic Applications[J]. Toxins (Basel), 2024, 16(6): 261. DOI:10.3390/toxins16060261.
[16]Vinehout K, Tynes K, Sotelo MR, et al. Changes in Cortical Activity in Stroke Survivors Undergoing Botulinum Neurotoxin Therapy for Treatment of Focal Spasticity[J]. Front Rehabil Sci, 2021, 2: 735819. DOI:10.3389/fresc.2021.735819.
[17]Veverka T, Hok P, Trnečková M, et al. Interhemispheric parietal cortex connectivity reflects improvement in post-stroke spasticity due to treatment with botulinum toxin-A[J]. J Neurol Sci, 2023, 446: 120588. DOI:10.1016/j.jns.2023.120588.
[18]Weise D, Weise CM, Naumann M. Central Effects of Botulinum Neurotoxin-Evidence from Human Studies[J]. Toxins (Basel), 2019, 11(1): 21. DOI:10.3390/toxins11010021.
[19] Cummins DD, Park HJ, Panov F. Neurosurgical treatment of spasticity: a potential return to the cerebellum[J]. Neurosurg Focus, 2024, 56(6): E3. DOI:10.3171/2024.3.FOCUS2446.
[20] Masakado Y, Abo M, Kondo K, et al. Efficacy and safety of incobotulinumtoxinA in post-stroke upper-limb spasticity in Japanese subjects: results from a randomized, double-blind, placebo-controlled study (J-PURE)[J]. J Neurol, 2020, 267(7): 2029-2041. DOI:10.1007/s00415-020-09777-5.
[21] Intiso D, Simone V, Bartolo M, et al. High Dosage of Botulinum Toxin Type A in Adult Subjects with Spasticity Following Acquired Central Nervous System Damage: Where Are We at?[J]. Toxins (Basel), 2020, 12(5): 315. DOI:10.3390/toxins12050315.
[22]Yan Y, Fu X, Xie X, et al. Hip Adductor Intramuscular Nerve Distribution Pattern of Children: A Guide for BTX-A Treatment to Muscle Spasticity in Cerebral Palsy[J]. Front Neurol, 2019, 10: 616. DOI:10.3389/fneur.2019.00616.
[23]Ibrahim AA, Ollenschläger M, Klebe S, et al. Mobile digital gait analysis captures effects of botulinum toxin in hereditary spastic paraplegia[J]. Eur J Neurol, 2024, 31(8): e16367. DOI:10.1111/ene.163 67.
[24] Zorowitz RD, Jacinto J, Ashford S, et al. Muscle selection and dosing in patients undergoing treatment with abobotulinumtoxinA for lower limb spasticity in real-world practice[J]. J Rehabil Med, 2025, 57: jrm42605. DOI:10.2340/jrm.v57.42605.
[25]Gresits OZ, Vezér M, Engh MA, et al. Limited evidence of functional benefit after upper limb Botulinum Toxin treatment in children with cerebral palsy: systematic review and meta-analysis[J]. Am J Phys Med Rehabil, 2025, 104(2): 108-116. DOI:10.1097/PHM0000000000002533.
[26]Aygün Bilecik N, Tuna S, Karataş Ö, Balcı N. The impact of repeated applications of Botulinum Toxin A on the spasticity of the upper limb in stroke patient, Cohort study[J]. J Clin Med, 2025, 14(8): 2735. DOI:10.3390/jcm14082735.
[27]Rahman E, Carruthers JDA, Rao P, et al. Predictive Modeling of Immunogenicity to Botulinum Toxin A Treatments for Glabellar Lines[J]. Plast Reconstr Surg, 2025, 155(4): 676e-688e. DOI:10.1097/PRS.0000000000011748.
[28]Ellenbogen A, Hauser RA, Patel AT, et al. Efficacy Remaining at Time of Requested Re-Treatment for Cervical Dystonia: A Potential New Treatment Paradigm with Daxibotulinum toxin A[J]. Toxins (Basel), 2025, 17(3):133. DOI:10.3390/toxins17030133.
[29]Tsuchiya M, Morita A, Hara Y. Effect of Dual Therapy with Botulinum Toxin A Injection and Electromyography-controlled Functional Electrical Stimulation on Active Function in the Spastic Paretic Hand[J]. J Nippon Med Sch, 2016, 83(1): 15-23. DOI:10.1272/jnms.83.15.
[30]Déniz A, Saavedra P, Marrero I, et al. Effectiveness of Unfocused vs. Focal Shock Waves Combined with Botulinum Toxin on Spasticity in Brain-Damaged Patients[J]. Toxins (Basel), 2025, 17(5): 209. DOI: 10.3390/toxins17050209.
[31]Takeuchi K, Takebayashi T, Hanioka D, et al. Comparison of tendon and muscle belly vibratory stimulation in the treatment of post-stroke upper extremity spasticity: a retrospective observational pilot study[J]. Sci Rep, 2024,14(1): 4151. DOI:10.1038/s41598-024-54815-1.
[32]Jacinto J, Balbert A, Bensmail D, et al. Selecting Goals and Target Muscles for Botulinum Toxin A Injection Using the Goal Oriented Facilitated Approach to Spasticity Treatment (GO-FAST) Tool[J]. Toxins (Basel), 2023, 15(12): 676. DOI:10.3390/toxins15120676.
[33]周家宇, 杨胜波. 前臂前群肌痉挛神经阻滞靶点定位的研究进展[J]. 中国临床解剖学杂志, 2023, 41(4):496-498. DOI:10.13418/j.issn. 1001-165x.2023.4.23.
Zhou JY, Yang SB. Progress on the localization of nerve block target for anterior forearm muscles spasticity[J]. Chin J Clin Anat, 2023, 41(4): 496-498. DOI: 10.13418/j.issn.1001-165x.2023.4.23.
[34]Hauret I, Dobija L, Givron P, et al. Effectiveness of Ultrasound-guided VS Electrical-stimulation-guided Botulinum Toxin Injections in Triceps Surae Spasticity after Stroke: A Randomized Controlled Study[J]. J Rehabil Med, 2023, 55: jrm11963. DOI:10.2340/jrm.v55.11963.
[35]Graciani MT, Costa FHR, Rosso ALZ, et al. EMG versus US: a randomized clinical trial comparing the efficacy in guiding botulinum toxin treatment in cervical dystonia[J]. Arq Neuropsiquiatr, 2025, 83(6): 1-8. DOI:10.1055/s-0045-1809542.
[36]Albert AM, Magimairaj HP, Lakshmanan J, et al. Localizing motor entry points of adductor muscles of thigh for motor point procedures in the treatment of adductor spasticity[J]. Anat Cell Biol, 2024, 57(4): 503-510. DOI:10.5115/acb.24.065.
[37]Chen R, He L, He X, et al. Experimental study of the center of the intramuscular nerve dense region of the masseter muscle as the optimal botulinum neurotoxin A injection site[J]. Ann Anat, 2025, 261: 152697. DOI:10.1016/j.aanat.2025.152697.
[38]He X, Wen S, Liu X, et al. Optimal target localization for botulinum toxin A in treating splenius muscles dystonia based on the distribution of intramuscular nerves and spindles[J]. Anat Sci Int, 2025, 101(1): 44-53. DOI:10.1007/s12565-025-00831-8.
[39]Bavikatte G, Esquenazi A, Dimyan MA, et al. Safety and Real-World Dosing of OnabotulinumtoxinA for the Treatment of Adult Spasticity: Post Hoc Analysis of the Adult Spasticity International Registry Study[J]. Am J Phys Med Rehabil, 2024, 103(7): 580-587. DOI:10.1097/PHM.0000000000002410.
[40]Hwang IS, Ryu JW, Jin S, et al. Long-Term Enhancement of Botulinum Toxin Injections for Post-Stroke Spasticity by Use of Stretching Exercises-A Randomized Controlled Tria[J]l. Toxins (Basel), 2024, 16(6):267. DOI:10.3390/toxins16060267.
[41]Li HX, Xu K, Chen SL, et al. Current techniques for the treatment of spasticity and their effectiveness[J]. EFORT Open Rev, 2025, 10(5): 237-249. DOI:10.1530/EOR-2024-0156.
[42]Sagerfors M, Blaszczyk I, Chemnitz A, et al. Trends in spasticity-reducing surgery and botulinum toxin treatment for post-stroke spasticity: a register study on 6,258 patients in Sweden, 2010-2021[J]. J Rehabil Med, 2025, 57: jrm42684. DOI:10.2340/jrm.v57.42684.
[43]Leblong E, Piette P, Anne C, et al. Switox: Retrospective Analysis of Botulinum Toxin Switching in Management of Spasticity[J]. Toxins (Basel), 2025, 17(3): 103. DOI:10.3390/toxins17030103.
[44]Multani I, Manji J, Hastings-Ison T, et al. Botulinum Toxin in the Management of Children with Cerebral Palsy[J]. Paediatr Drugs. 2019, 21(4): 261-281. DOI:10.1007/s40272-019-00344-8.
[45]Li Z, Chong Y, Jin L, et al. Botulinum Toxin Treatment for Calf Contouring Based on the Study of Combined Injection of Gastrocnemius and Soleus[J]. Aesthet Surg J, 2024, 44(5): 545-555. DOI:10.1093/asj/sjad365.
[46]Krasavina DA, Ivanov DO, Orlova OR, et al. [Sequential use of botulinum toxin A and bovhyaluronidase azoximer in the correction of post-stroke spasticity][J]. Zh Nevrol Psikhiatr Im S S Korsakova, 2025, 125(2): 80-85. DOI:10.17116/jnevro202512502180.
[47]Spina S, Facciorusso S, Cinone N, et al. Integrating Telemedicine in Botulinum Toxin Type-A Treatment for Spasticity Management: Perspectives and Challenges from Italian Healthcare Professionals[J]. Toxins (Basel), 2024, 16(12): 529. DOI:10.3390/toxins16120529.