Comparative Efficacy of Vibration, Ice, and Topical Anesthesia for Reducing Botulinum Toxin Injection Pain
A Systematic Review and Network Meta-Analysis
Keywords:
Botulinum Toxins, Type A, Pain; Injection Site Reaction, Anesthesia, Local.Abstract
Background: Botulinum toxin (BoNT) injection pain is a barrier to patient satisfaction. Non-invasive analgesics like ice, vibration, and topical anesthesia are common, but their relative efficacy is unknown. We aimed to compare and rank these three interventions for BoNT injection pain via a systematic review and network meta-analysis (NMA).
Methods: We followed PRISMA-NMA guidelines. A systematic search (inception to August 2025) was conducted in major databases, including PubMed, Scopus, and Embase, for studies of BoNT injection pain. Randomized controlled trials and comparative studies comparing ice, vibration, or topical anesthesia were included. A network meta-analysis was performed using a random-effects model to assess efficacy (pain scores), safety, and satisfaction. Interventions were ranked by P-score.
Results: Twenty-two studies were included. The NMA demonstrated that ice application was the most effective analgesic, consistently ranking first (P-score = 0.8544). Topical anesthesia ranked second (P-score = 0.7542), while vibration was not significantly different from no-intervention controls. All interventions had an excellent safety profile, with pooled adverse event rates near 0%. Paradoxically, patient satisfaction was lowest for ice (19%) and highest for vibration (59%) and topical anesthesia (55%).
Conclusion: Ice is the most effective non-invasive intervention for reducing BoNT injection pain. However, it is associated with the lowest patient satisfaction, while less effective methods are preferred. Clinicians should tailor interventions to balance objective pain relief with patient comfort and preference.
References
1. Dover, J.S., et al., Botulinum Toxin in Aesthetic Medicine: Myths and Realities. Dermatol Surg, 2018. 44(2): p. 249-260, Available at: https://10.1097/dss.0000000000001277
2. Escher, C.M., et al., Botulinum toxin in the management of chronic migraine: clinical evidence and experience. Ther Adv Neurol Disord, 2017. 10(2): p. 127-135, Available at: https://10.1177/1756285616677005
3. Chen, Y.T., et al., The Effects of Botulinum Toxin Injections on Spasticity and Motor Performance in Chronic Stroke with Spastic Hemiplegia. Toxins (Basel), 2020. 12(8)Available at: https://10.3390/toxins12080492
4. Witmanowski, H. and K. Błochowiak, The whole truth about botulinum toxin - a review. Postepy Dermatol Alergol, 2020. 37(6): p. 853-861, Available at: https://10.5114/ada.2019.82795
5. Flynn, T.C., Botulinum toxin: examining duration of effect in facial aesthetic applications. Am J Clin Dermatol, 2010. 11(3): p. 183-99, Available at: https://10.2165/11530110-000000000-00000
6. Usach, I., et al., Subcutaneous Injection of Drugs: Literature Review of Factors Influencing Pain Sensation at the Injection Site. Adv Ther, 2019. 36(11): p. 2986-2996, Available at: https://10.1007/s12325-019-01101-6
7. Wang, J. and L.V. Doan, Clinical pain management: Current practice and recent innovations in research. Cell Reports Medicine, 2024. 5(10): p. 101786, Available at: https://https://doi.org/10.1016/j.xcrm.2024.101786
8. Ghorbanzadeh, S., et al., Effect of vibratory stimulation on pain during local anesthesia injections: a clinical trial. Restor Dent Endod, 2019. 44(4): p. e40, Available at: https://10.5395/rde.2019.44.e40
9. Mahshidfar, B., et al., Ice Reduces Needle-Stick Pain Associated With Local Anesthetic Injection. Anesth Pain Med, 2016. 6(5): p. e38293, Available at: https://10.5812/aapm.38293
10. Aksoy, F. and S. Tosun, Effects of different topical anesthetics on pain from needle insertion and injection, and the influence of anxiety in patients awaiting endodontic treatment. Restor Dent Endod, 2022. 47(3): p. e25, Available at: https://10.5395/rde.2022.47.e25
11. Hutton, B., F. Catalá-López, and D. Moher, The PRISMA statement extension for systematic reviews incorporating network meta-analysis: PRISMA-NMA. Medicina Clínica (English Edition), 2016. 147(6): p. 262-266, Available at: https://https://doi.org/10.1016/j.medcle.2016.10.003
12. Linder, J.S., et al., Skin Cooling Before Periocular Botulinum Toxin A Injection. Ophthalmic Plastic & Reconstructive Surgery, 2002. 18(6)Available at:
13. Sarifakioglu, N. and E. Sarifakioglu, Evaluating the effects of ice application on the pain felt during botulinum toxin type-a injections: a prospective, randomized, single-blind controlled trial. Annals of plastic surgery, 2004. 53(6): p. 543-546, Available at:
14. Elibol, O., et al., Efficacy of skin cooling and EMLA cream application for pain relief of periocular botulinum toxin injection. Ophthalmic Plastic & Reconstructive Surgery, 2007. 23(2): p. 130-133, Available at:
15. Skiveren, J., E. Kjaerby, and H.N. Larsen, Cooling by frozen gel pack as pain relief during treatment of axillary hyperhidrosis with botulinum toxin a injections. Acta dermato-venereologica, 2008. 88(4)Available at:
16. Saeliw, P., P. Preechawai, and N. Aui-aree, Evaluating the effects of ice application on patient comfort before and after botulinum toxin type A injections. Medical journal of the Medical Association of Thailand, 2010. 93(10): p. 1200, Available at:
17. Engel, S.J., A.M. Afifi, and J.E. Zins, Botulinum toxin injection pain relief using a topical anesthetic skin refrigerant. Journal of plastic, reconstructive & aesthetic surgery, 2010. 63(9): p. 1443-1446, Available at:
18. Sharma, P., C.N. Czyz, and A.E. Wulc, Investigating the efficacy of vibration anesthesia to reduce pain from cosmetic botulinum toxin injections. Aesthetic surgery journal, 2011. 31(8): p. 966-971, Available at:
19. Fung, S., et al., Effect of topical anesthetics on needle insertion pain during botulinum toxin type A injections for limb spasticity. Archives of physical medicine and rehabilitation, 2012. 93(9): p. 1643-1647, Available at:
20. Dixit, S., et al., Ice anaesthesia in procedural dermatology. Australasian Journal of Dermatology, 2013. 54(4): p. 273-276, Available at:
21. Mally, P., et al., Vibration anesthesia for the reduction of pain with facial dermal filler injections. Aesthetic plastic surgery, 2014. 38(2): p. 413-418, Available at:
22. Pucks, N., et al., Cutaneous cooling to manage botulinum toxin injection-associated pain in patients with facial palsy: a randomised controlled trial. Journal of Plastic, Reconstructive & Aesthetic Surgery, 2015. 68(12): p. 1701-1705, Available at:
23. Kuwahara, H. and R. Ogawa, Using a vibration device to ease pain during facial needling and injection. Eplasty, 2016. 16: p. e9, Available at:
24. Alsantali, A., A comparative trial of ice application versus EMLA cream in alleviation of pain during botulinum toxin injections for palmar hyperhidrosis. Clinical, Cosmetic and Investigational Dermatology, 2018: p. 137-140, Available at:
25. Chorney, S.R., J.A. Villwock, and A.C. Suryadevara, Vibration versus ice to reduce cosmetic Botulinum toxin injection pain—a randomized controlled trial. Ear, Nose & Throat Journal, 2019. 98(6): p. 351-355, Available at:
26. ÖZÜCer, B. and O.H. ÇAm. A clinical comparison of eMLA cream and vibratory anesthetic device application for alleviation of pain associated with botulinum toxin injection for the masseter muscle hypertrophy.
27. Jung, G.S. and H.S. Kim, A novel technique to reduce pain from intradermal injection of botulinum toxin type A. Plastic and Reconstructive Surgery–Global Open, 2021. 9(2): p. e3417, Available at:
28. Sarkarat, F., et al., Effects of lidocaine incorporation (without epinephrine) on pain and 2-week complications of botulinum toxin: a double-blind randomized placebo-controlled clinical trial. Scientific Reports, 2023. 13(1): p. 7812, Available at:
29. Tempatarachoke, O., A Comparative Study of Pain Intensity in Patients Receiving Cooling Botulinum Toxin (BTX) and Non-cooling BTX. Eye South East Asia, 2024. 19(1): p. 12-18, Available at: https://10.36281/2024010203
30. Marani, A., et al., Pain control during the treatment of primary palmar hyperhidrosis with botulinum toxin a by a topical application of liposomal lidocaine: clinical effectiveness. Toxins, 2024. 16(1): p. 28, Available at:
31. Hua, T., et al., Is Vibration Anesthesia Effective and Safe for Pain Reduction in Botulinum Toxin Injection? A Randomized Split-Face Controlled Trial and Cadaver Experiment. Aesthetic Surgery Journal, 2025. 45(4): p. NP113-NP118, Available at:
32. Li, Y., et al., Investigation of the efficacy and safety of topical vibration anesthesia to reduce pain from cosmetic botulinum toxin A injections in Chinese patients: a multicenter, randomized, self-controlled study. Dermatologic Surgery, 2017. 43: p. S329-S335, Available at:
33. Weiss, R.A. and P.T. Lavin, Reduction of pain and anxiety prior to botulinum toxin injections with a new topical anesthetic method. Ophthalmic Plast Reconstr Surg, 2009. 25(3): p. 173-7, Available at: https://10.1097/IOP.0b013e3181a145ca
34. Fillingim, R.B., Individual differences in pain: understanding the mosaic that makes pain personal. Pain, 2017. 158 Suppl 1(Suppl 1): p. S11-s18, Available at: https://10.1097/j.pain.0000000000000775
35. Rn, p., Effect of local application of cold or heat for relief of pricking pain. Nursing & Health Sciences, 2002. 4: p. 97-105, Available at: https://10.1046/j.1442-2018.2002.00112.x
36. Park, R., et al., Cryoanalgesia for postsurgical pain relief in adults: A systematic review and meta-analysis. Ann Med Surg (Lond), 2021. 69: p. 102689, Available at: https://10.1016/j.amsu.2021.102689
37. Söylev, M.F., et al., Anesthesia with EMLA cream for botulinum A toxin injection into eyelids. Ophthalmologica, 2002. 216(5): p. 355-8, Available at: https://10.1159/000066186
38. Doi, K., Y. Ueda, and N. Imamachi, Use of EMLA cream for skin anesthesia and epidural insertion in the patients with cesarean delivery: A prospective double-blind randomized clinical trial. Saudi J Anaesth, 2022. 16(2): p. 145-149, Available at: https://10.4103/sja.sja_728_21
39. Comite, S.L., S. Rahaman, and M. Malkowiak, Vibration Anesthesia During Invasive Procedures: A Meta-analysis. J Clin Aesthet Dermatol, 2024. 17(10): p. 29-40, Available at:
40. Guney, K., B. Sezgin, and R. Yavuzer, The Efficacy of Vibration Anesthesia on Reducing Pain Levels During Lip Augmentation: Worth the Buzz? Aesthet Surg J, 2017. 37(9): p. 1044-1048, Available at: https://10.1093/asj/sjx073
41. Mally, P., et al., Vibration Anesthesia for the Reduction of Pain with Facial Dermal Filler Injections. Aesthetic plastic surgery, 2014. 38Available at: https://10.1007/s00266-013-0264-4
42. Mao, P., et al., Effect and safety profile of topical lidocaine on post-surgical neuropathic pain and quality of life: A systematic review and meta-analysis. J Clin Anesth, 2024. 92: p. 111219, Available at: https://10.1016/j.jclinane.2023.111219
43. Herrera, M.A.B., J.M.M. Vives, and A. Marti, Clinical Evolution and Safety of a Cryotherapy-Based Spray for Mild to Moderate Joint and Muscle Pain: A Descriptive Observational Study. International Journal of Sports Physical Therapy, 2025. 20(2): p. 243, Available at:
44. Rasooli, F., et al., The assessment of ice pack effect in pain reduction during digital nerve block: A randomized clinical study. Turkish Journal of Emergency Medicine, 2020. 20(2)Available at:
45. Rękas-Dudziak, A., et al., The use of local anaesthetics in dermatology, aesthetic medicine and plastic surgery: review of the literature. Postepy Dermatol Alergol, 2023. 40(1): p. 22-27, Available at: https://10.5114/ada.2023.125221
Downloads
Published
How to Cite
License
Copyright (c) 2026 Rena Abualjamal, Dr abdulaziz Asiry, Khalid Salah Menshawi, Abdulgafoor Gushgari, Abrar Abduljalil Mohammed Altayeb, Abdullah hisham Al Faryan, Nada zinaf alotaibi, Tala Aiman Zamil, Arwa A. Aljohani

This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- The Author retains copyright in the Work, where the term “Work” shall include all digital objects that may result in subsequent electronic publication or distribution.
- Upon acceptance of the Work, the author shall grant to the Publisher the right of first publication of the Work.
- The Author shall grant to the Publisher and its agents the nonexclusive perpetual right and license to publish, archive, and make accessible the Work in whole or in part in all forms of media now or hereafter known under a Creative Commons Attribution 4.0 International License or its equivalent, which, for the avoidance of doubt, allows others to copy, distribute, and transmit the Work under the following conditions:
- Attribution—other users must attribute the Work in the manner specified by the author as indicated on the journal Web site; with the understanding that the above condition can be waived with permission from the Author and that where the Work or any of its elements is in the public domain under applicable law, that status is in no way affected by the license.
- The Author is able to enter into separate, additional contractual arrangements for the nonexclusive distribution of the journal's published version of the Work (e.g., post it to an institutional repository or publish it in a book), as long as there is provided in the document an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post online a prepublication manuscript (but not the Publisher’s final formatted PDF version of the Work) in institutional repositories or on their Websites prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work. Any such posting made before acceptance and publication of the Work shall be updated upon publication to include a reference to the Publisher-assigned DOI (Digital Object Identifier) and a link to the online abstract for the final published Work in the Journal.
- Upon Publisher’s request, the Author agrees to furnish promptly to Publisher, at the Author’s own expense, written evidence of the permissions, licenses, and consents for use of third-party material included within the Work, except as determined by Publisher to be covered by the principles of Fair Use.
- The Author represents and warrants that:
- the Work is the Author’s original work;
- the Author has not transferred, and will not transfer, exclusive rights in the Work to any third party;
- the Work is not pending review or under consideration by another publisher;
- the Work has not previously been published;
- the Work contains no misrepresentation or infringement of the Work or property of other authors or third parties; and
- the Work contains no libel, invasion of privacy, or other unlawful matter.
- The Author agrees to indemnify and hold Publisher harmless from the Author’s breach of the representations and warranties contained in Paragraph 6 above, as well as any claim or proceeding relating to Publisher’s use and publication of any content contained in the Work, including third-party content.
Enforcement of copyright
The IJMS takes the protection of copyright very seriously.
If the IJMS discovers that you have used its copyright materials in contravention of the license above, the IJMS may bring legal proceedings against you seeking reparation and an injunction to stop you using those materials. You could also be ordered to pay legal costs.
If you become aware of any use of the IJMS' copyright materials that contravenes or may contravene the license above, please report this by email to contact@ijms.org
Infringing material
If you become aware of any material on the website that you believe infringes your or any other person's copyright, please report this by email to contact@ijms.org



