Objective To conduct a systematic evaluation of the safety of botulinum toxin type A (BTX-A) in the treatment of pain.

Methods A computer-based literature search was performed in the CNKI, VIP, Wanfang Data, SinoMed, PubMed, Cochrane Library, Embase,  and Web of Science databases for studies investigating adverse reactions associated with the intramuscular administration of BTX-A for pain management, covering the period from January 2013 to December 2025. Meta-analysis was performed using RevMan 5.4 software.

Results A total of 18 randomized controlled trials involving 1,164 patients were included; among these, 112 cases of adverse reactions related to the intramuscular administration of BTX-A were identified. The adverse reactions primarily affected the following systems: skin and appendages, central and peripheral nervous systems, urinary system, digestive system, and musculoskeletal system. Specific adverse reactions mainly included ptosis of the upper eyelid, local muscle weakness, pain at the injection site, and neck weakness/fatigue. The Meta-analysis results demonstrated that there was no statistically significant difference in the overall incidence of adverse reactions between BTX-A and the control group (P>0.05). Subgroup analysis revealed that the risk of adverse reactions to BTX-A was significantly lower in the headache subgroup compared to the control group [RR=0.59,95%CI (0.42, 0.82), P=0.002]; however, no statistically significant difference in adverse reaction rates was observed between the two groups in the neuralgia or other pain subgroups (P>0.05).

Conclusion The overall clinical safety profile of BTX-A for the treatment of various types of migraine, neuralgia, and other pain conditions is favorable. Adverse reactions to BTX-A are predominantly mild local reactions; however, safety concerns associated with its use still exist. Clinically, it is essential to strictly follow operational guidelines for neurotoxic medications, implement comprehensive medication monitoring throughout treatment, and ensure the therapy's safety and efficacy.

1. PirazziniM, RossettoO, EleopraR, et al. Botulinum neurotoxins: biology, pharmacology, and toxicology[J]. Pharmacol Rev, 2017, 69(2): 200-235. DOI: 10.1124/pr.116.012658.

2. IntisoD, BascianiM, SantamatoA, et al. Botulinum toxin type A for the treatment of neuropathic pain in neuro-rehabilitation[J]. Toxins, 2015, 7(7): 2454-2480. DOI: 10.3390/toxins7072454.

3. XiaoL, MackeyS, HuiH, et al. Subcutaneous injection of botulinum toxin A is beneficial in postherpetic neuralgia[J]. Pain Med, 2010, 11(12): 1827-1833. DOI: 10.1111/j.1526-4637.2010.01003.x.

4. 中国医师协会神经内科医师分会, 中国研究型医院学会头痛与感觉障碍专业委员会. 中国偏头痛诊治指南 (2022 版)[J]. 中国疼痛医学杂志, 2022, 28(12): 881-898.Chinese Medical Association Neurology Branch, Chinese Research Hospital Association Headache and Sensory Disorders Professional Committee. Chinese migraine diagnosis and treatment guidelines (2022 edition)[J]. Chinese Journal of Pain Medicine, 2022, 28(12): 881-898. DOI: 10.3969/j.issn.1006-9852.2022.12.001.

5. 蒋仙国, 潘元美, 潘丽珍, 等. A 型肉毒毒素治疗慢性偏头痛的专家共识[J]. 神经病学与神经康复学杂志,2026, 22(2): 77-89.JiangXG, PanYM, PanLZ, et al. Expert consensus on the use of botulinum toxin type A for the treatment of chronic migraine[J]. Journal of Neurology and Neurorehabilitation, 2026, 22(2): 77-89. DOI: 10.12022/jnnr.2025-0315.

6. JacksonJL, KuriyamaA, HayashinoY. Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis[J]. JAMA, 2012, 307(16): 1736-1745. DOI: 10.1001/jama.2012.505.

7. 中华医学会神经病学分会头痛协作组, 王永刚, 刘恺鸣. 中国成人偏头痛预防性治疗药物临床对照试验专家共识[J]. 中华内科杂志, 2023, 62(5): 481-492.Headache Collaborative Group of Chinese Medical Association Neurology Branch, WangYG, LiuKM, et al. Expert consensus on clinical controlled trials of prophylactic medications for migraine in Chinese adults[J]. Chinese Journal of Internal Medicine, 2023, 62(5): 481-492. DOI: 10.3760/cma.j.cn112138-20221031-00805.

8. 李冰冰, 孟祥慧, 李欣, 等. A型肉毒毒素治疗带状疱疹后遗神经痛的研究进展[J]. 牡丹江医科大学学报, 2025, 46(3): 117‑120. [LiBB, MengXH, LiX, et al. Research progress of botulinum toxin type A in the treatment of postherpetic neuralgia[J]. Journal of Mudanjiang Medical University, 2025, 46(3): 117-120.DOI: 10.13799/j.cnki.mdjdyxb.2025.03.024.

9. 刘明煦, 吴兰香, 田胜, 等. A型肉毒毒素治疗慢性偏头痛合并三叉神经痛1例[J]. 中国疼痛医学杂志, 2023, 29(8): 636-638.LiuMX, WuLX, TianS, et al. One case of chronic migraine combined with trigeminal neuralgia treated by botulinum toxin type A[J]. Chinese Journal of Pain Medicine, 2023, 29(8): 636-638. DOI: 10.3969/j.issn.1006-9852.2023.08.012.

10. KimSR, ChangM, KimAH, et al. Effect of botulinum toxin on masticatory muscle pain in patients with temporomandibular disorders: a randomized, double-blind, placebo-controlled pilot study[J]. Toxins, 2023, 15(10): 589. DOI: 10.3390/toxins15100597.

11. CrespiJ, BratbakD, DodickDW, et al. Pilot study of injection of onabotulinumtoxinA toward the sphenopalatine ganglion for the treatment of classical trigeminal neuralgia[J]. Headache, 2019, 59(8): 1229-1239. DOI: 10.1111/head.13608.

12. 李华亮, 潘平雷, 陈佳慧, 等. A型肉毒毒素治疗三叉神经痛和带状疱疹后神经痛的临床疗效[J]. 中国临床医学, 2020, 27(5): 834‑836. [LiHL, PanPL, ChenJH, et al. Clinical efficacy of botulinum toxin type A for trigeminal neuralgia and postherpetic neuralgia[J]. Chinese Journal of Clinical Medicine, 2020, 27(5): 834-836.DOI: 10.12025/j.issn.1008-6358.2020.20200752.

13. 武晓可, 史萌萌, 张海峰, 等. A型肉毒毒素治疗三叉神经痛的疗效分析[J]. 中华神经科杂志, 2025, 58(10): 1087-1094.WuXK, ShiMM, ZhangHF, et al. Efficacy analysis of botulinum toxin type A in the treatment of trigeminal neuralgia[J]. Chinese Journal of Neurology, 2025, 58(10): 1087-1094. DOI: 10.3760/cma.j.cn113694-20250123-00054.

14. 刘清军. 《三叉神经痛诊疗中国专家共识》解读[J]. 中国现代神经疾病杂志, 2018, 18(9): 643-646.LiuQJ. Interpretation of Chinese expert consensus on diagnosis and treatment of trigeminal neuralgia[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2018, 18(9): 643-646. DOI: 10.3969/j.issn.1672-6731.2018.09.003.

15. HerdCP, TomlinsonCL, RickC, et al. Cochrane systematic review and meta-analysis of botulinum toxin for the prevention of migraine[J]. BMJ Open, 2019, 9(7): e027953. DOI: 10.1136/bmjopen-2018-027953.

16. SpruijtMA, KlerkxWM, KelderJC, et al. The efficacy of botulinum toxin A injections in pelvic floor muscles in chronic pelvic pain patients: a systematic review and meta-analysis[J]. Int Urogynecol J, 2022, 33(11): 2951-2961. DOI: 10.1007/s00192-022-05115-7.

17. LiTT, LiuZY, XiongL, et al. Clinical efficacy of botulinum toxin type A in the treatment of fasciitis pain: a systematic review and meta-analysis[J]. Medicine (Baltimore), 2023, 102(30): e34461. DOI: 10.1097/md.0000000000034461.

18. HsuPC, WuWT, HanDS, et al. Comparative effectiveness of botulinum toxin injection for chronic shoulder pain: a meta-analysis of randomized controlled trials[J]. Toxins, 2020, 12(4): 237. DOI: 10.3390/toxins12040251.

19. 潘昱睿, 王瑜元, 白玉龙, 等. A型肉毒毒素作用于神经胶质细胞缓解神经病理性疼痛机制的研究进展[J]. 上海医药, 2024, 45(3): 9-15.PanYR, WangYY, BaiYL, et al. Research progress on the mechanism of botulinum toxin type A acting on glial cells to relieve neuropathic pain[J]. Shanghai Medical and Pharmaceutical Journal, 2024, 45(3): 9-15. DOI: 10.3969/j.issn.1006-1533.2024.03.003.

20. 何磊, 张悦, 欧册华, 等. A型肉毒毒素联合脉冲射频治疗带状疱疹后神经痛的疗效及安全性[J]. 实用医学杂志, 2024, 40(6): 833-837.HeL, ZhangY, OuCH, et al. Efficacy and safety of botulinum toxin type A combined with pulsed radiofrequency for postherpetic neuralgia[J]. Journal of Practical Medicine, 2024, 40(6): 833-837. DOI: 10.3969/j.issn.1006-5725.2024.06.017.

21. 胡悦育. A型肉毒毒素治疗偏头痛的临床研究[J]. 中国新药与临床杂志, 2005, 24(2): 165‑168. [HuYY. Clinical study of botulinum toxin type A in the treatment of migraine[J]. Chinese Journal of New Drugs and Clinical Remedies, 2005, 24(2): 165-168.DOI: 10.3969/j.issn.1007-7669.2005.02.025.

22. TurkelCC, AuroraS, DienerHC, et al. Treatment of chronic migraine with Botox (onabotulinumtoxinA): development, insights, and impact[J]. Medicine (Baltimore), 2023, 102(S1): e32600. DOI: 10.1097/MD.0000000000032600.

23. WangC, ZhangQ, WangR, et al. Botulinum toxin type A for diabetic peripheral neuropathy pain: a systematic review and meta-analysis[J]. J Pain Res, 2021, 14: 3855-3863. DOI: 10.21 47/JPR.S340390.

24. LeeMJ, Al-karagholiMA, ReuterU. New migraine prophylactic drugs: current evidence and practical suggestions for non-responders to prior therapy[J]. Cephalalgia, 2023, 43(2): 33310 24221146315. DOI: 10.1177/03331024221146315.

25. DhanasekaraCS, PayberahD, ChyuJY, et al. The effectiveness of botulinum toxin for chronic tension-type headache prophylaxis: a systematic review and meta-analysis[J]. Cephalalgia, 2023, 43(3): 3331024221150231. DOI: 10.1177/03331024221150231.

26. 张元文, 高磊. A型肉毒毒素治疗慢性骨关节炎疼痛的应用和研究进展[J]. 中华物理医学与康复杂志, 2024, 46(11): 1045-1048.ZhangYW, GaoL. Application and research progress of botulinum toxin type A in the treatment of chronic osteoarthritis pain[J]. Chinese Journal of Physical Medicine and Rehabilitation, 2024, 46(11): 1045-1048. DOI: 10.3760/cma.j.cn421666-20210713-00714.

27. ShaterianN, ShaterianN, GhanaatpishehA, et al. Botox (onabotulinumtoxinA) for treatment of migraine symptoms: a systematic review[J]. Pain Research and Management, 2022, 2022: 9984017. DOI: 10.1155/2022/3284446.

28. MengF, PengK, YangJP, et al. Botulinum toxin-A for the treatment of neuralgia: a systematic review and Meta-analysis[J]. J Pain Res, 2018, 11: 2343-2350. DOI: 10.2147/JPR.S168650.

29. 李荣荣, 孙妍, 李燕, 等. A型肉毒毒素治疗慢性头痛的临床效果及安全性评价[J]. 中文科技期刊数据库(文摘版)医药卫生, 2023, (12): 148-151.LiRR, SunY, LiY, et al. Clinical effect and safety evaluation of botulinum toxin type A in the treatment of chronic headache[J]. Chinese Science and Technology Journal Database (Abstract Edition) Medicine and Health, 2023, (12): 148-151. DOI: 10.12238/j.issn.2096-361X.2023.12.047.

30. 秦敬翠. A型肉毒毒素局部注射治疗慢性偏头疼共病焦虑临床疗效观察[J]. 中西医结合心血管病电子杂志, 2020, 8(7): 74, 83.QinJC. Clinical observation on local injection of botulinum toxin type A in the treatment of chronic migraine comorbid with anxiety[J]. Electronic Journal of Integrated Cardiovascular Disease, 2020, 8(7): 74, 83. DOI: 10.16282/j.cnki.cn11-9331/r.2020.07.053.

31. 张璇, 冯文霞, 郭鹏, 等. A型肉毒毒素注射对合并面肌痉挛的紧张型头痛的疗效研究[J]. 解放军预防医学杂志, 2019, 37(3): 111-112.ZhangX, FengWX, GuoP, et al. Therapeutic effect of botulinum toxin type A injection on tension-type headache combined with hemifacial spasm[J]. Journal of Preventive Medicine of Chinese People's Liberation Army, 2019, 37(3): 111-112. DOI: 10.13704/j.cnki.jyyx.2019.03.044.

32. 翟跃芬, 张茹, 吴海琴, 等. A型肉毒毒素注射治疗慢性紧张型头痛的临床对照研究[J]. 安徽医药, 2017, 21(5): 914-917.ZhaiYF, ZhangR, WuHQ, et al. Clinical controlled study of botulinum toxin type A injection in the treatment of chronic tension-type headache[J]. Anhui Medical and Pharmaceutical Journal, 2017, 21(5): 914-917. DOI: 10.3969/j.issn.1009-6469.2017.05.024.

33. NaderinabiB, SaberiA, HashemiM, et al. Acupuncture and botulinum toxin A injection in the treatment of chronic migraine: a randomized controlled study[J]. Caspian J Intern Med, 2017, 8(3): 196-204. DOI: 10.22088/cjim.8.3.196.

34. 王春辉, 崔超伟, 胡笑兴, 等. 综合护理A型肉毒毒素治疗慢性偏头痛的临床研究[J]. 中国现代药物应用, 2015, 9(24): 230-231.WangCH, CuiCW, HuXX, et al. Clinical study on comprehensive nursing combined with botulinum toxin type A for chronic migraine[J]. Chinese Journal of Modern Drug Application, 2015, 9(24): 230-231. DOI: 10.14164/j.cnki.cn11-5581/r.2015.24.176.

35. 郑结成, 黎宇, 梁圣江, 等. A型肉毒毒素联合复方倍他米松治疗带状疱疹后神经痛的临床观察[J]. 大医生, 2023, 8(19) : 67-70.ZhengJC, LiY, LiangSJ, et al. Clinical observation of botulinum toxin type A combined with compound betamethasone for postherpetic neuralgia[J]. Doctor, 2023, 8(19): 67-70. DOI: 10.3969/j.issn.2095-4408.2023.19.018.

36. ChenL, ZhangY, ChenY, et al. Efficacy and safety of botulinum toxin A and pulsed radiofrequency on postherpetic neuralgia: a randomized clinical trial[J]. Contrast Media Mol Imaging, 2022, 2022: 7682416. DOI: 10.1155/2022/1579937.

37. 曹腾腾, 叶蕾, 郑海霞, 等. 扳机点注射A型肉毒杆菌毒素联合活血通络胶囊治疗原发性三叉神经痛疗效及对血浆CGRP、SP、IL‑6、IL‑1β水平的影响[J]. 现代中西医结合杂志, 2018, 27(30): 3328-3331.CaoTT, YeL, ZhengHX, et al. Therapeutic effect of trigger-point injection of botulinum toxin type A combined with Huoxue Tongluo capsule on primary trigeminal neuralgia and its influence on plasma CGRP, SP, IL-6 and IL-1β levels[J]. Modern Journal of Integrated Traditional Chinese and Western Medicine, 2018, 27(30): 3328-3331. DOI: 10.3969/j.issn.1008-8849.2018.30.007.

38. AttalN, De AndradeDC, AdamF, et al. Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial[J]. Lancet Neurol, 2016, 15(6): 555-565. DOI: 10.1016/S1474-4422(16)00017-X.

39. ZhangH, LianY, MaY, et al. Two doses of botulinum toxin type A for the treatment of trigeminal neuralgia: observation of therapeutic effect from a randomized, double-blind, placebo-controlled trial[J]. J Headache Pain, 2014, 15(1): 65. DOI: 10.1186/1129-2377-15-65.

40. De La Torre Canales G, PoluhaRL, BonjardimLR, 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]. Sci Rep, 2024, 14(1): 4201. DOI: 10.1038/s41598-024-54906-z.

41. BrunoV, FreitasME, ManciniD, et al. Botulinum toxin type A for pain in advanced parkinson's disease[J]. Can J Neurol Sci, 2018, 45(1): 23-29. DOI: 10.1017/cjn.2017.245.

42. 程燕. A 型肉毒素治疗脑卒中后中枢性疼痛疗效的临床研究[D]. 南昌:南昌大学, 2022.

43. DessieSG, Von BargenE, HackerMR, et al. A randomized, double-blind, placebo-controlled trial of onabotulinumtoxinA trigger point injections for myofascial pelvic pain[J]. Am J Obstet Gynecol, 2019, 221(5): 517.e1-517.e9. DOI: 10.1016/j.ajog. 2019.06.044.

44. YooY, LeeCS, KimJ, et al. Botulinum toxin type A for lumbar sympathetic ganglion block in complex regional pain syndrome: a randomized trial[J]. Anesthesiology, 2022, 136(2): 314-325. DOI: 10.1097/ALN.0000000000004084.

45. JacobsonD, LowingK, KullanderK, et al. A first clinical trial on botulinum toxin-A for chronic muscle-related pain in cerebral palsy[J]. Front Neurol, 2021, 12: 648129. DOI: 10.3389/fneur.2021.696218.

46. GuoYH, KuanTS, ChenKL, et al. Comparison between steroid and 2 different sites of botulinum toxin injection in the treatment of lateral epicondylalgia: a randomized, double-blind, active drug-controlled pilot study[J]. Arch Phys Med Rehabil, 2017, 98(1): 36-42. DOI: 10.1016/j.apmr.2016. 08.475.