BOTULINUM TOXIN TYPE A (BoNT-A) FOR NEUROPATIC CANCER PAIN : A SYSTEMATIC REVIEW

BOTULINUM TOXIN TYPE A (BoNT-A) FOR NEUROPATIC CANCER PAIN : A SYSTEMATIC REVIEW

Authors

  • Christy Faculty of Medicine, University of Ciputra, Surabaya, East Java, Indonesia
  • Alvionita Muntholib Faculty of Medicine, University of Ciputra, Surabaya, East Java, Indonesia

Keywords:

Neuropathic cancer pain, Botulinum Toxin Type A (BoNT-A), pain management, cancer pain, systematic review

Abstract

Background: Neuropathic cancer pain (NCP) is a highly prevalent and debilitating condition affecting 30–50% of cancer patients undergoing treatment, with rates rising to 70–90% in advanced stages. Conventional pharmacotherapy, including opioids and adjuvants, often provides inadequate relief or causes significant adverse effects, highlighting the need for alternative therapeutic strategies. Botulinum Toxin Type A (BoNT-A) has emerged as a potential analgesic agent with a unique mechanism of action.

Objective: To systematically evaluate the effectiveness and safety of BoNT-A as a therapeutic option for neuropathic cancer pain.

Methods: A systematic review was conducted following PRISMA 2020 guidelines. Four databases (PubMed, ScienceDirect, Cochrane Library, ProQuest) were searched for randomized controlled trials (RCTs), pilot studies, and prospective cohort studies published between January 2015 and January 2025. Inclusion criteria were: studies assessing BoNT-A for NCP, quantitative pain outcomes, English language, and sample size ≥10 patients.

Results: Six studies (five RCTs and one prospective open-label study) involving 151 cancer patients were included. All studies reported statistically significant pain reduction following BoNT-A injection, with pain scores decreasing by 30–50% in most trials. Functional outcomes, such as arm mobility and quality of life, also improved. BoNT-A demonstrated a favorable safety profile, with only mild, transient local side effects. No serious systemic adverse events were reported.

Discussion: BoNT-A reduces NCP through multiple mechanisms: inhibition of acetylcholine, substance P, CGRP, and glutamate release; modulation of TRPV1 receptors; and central antinociceptive effects. Evidence supports its role as an effective adjunct or alternative to opioids, particularly in post-surgical and post-radiotherapy pain.

Conclusion: BoNT-A is effective and safe for managing neuropathic cancer pain. Further large-scale RCTs are needed to establish optimal dosing, long-term efficacy, and comparative effectiveness against standard therapies.

References

Mulvey, M.R., Paley, C.A., Schuberth, A. et al. Neuropathic Pain in Cancer: What Are the Current Guidelines?. Curr. Treat. Options in Oncol. 25, 1193–1202 (2024). https://doi.org/10.1007/s11864-024-01248-7

Bennett MI. Mechanism-based cancer-pain therapy. Pain. 2017;158(Suppl 1):S74–8. 2.

Nijs J, Lahousse A, Fernandez-de-Las-Penas C, Madeleine P, Fontaine C, Nishigami T, Desmedt C, Vanhoeij M, Mostaqim K, Cuesta-Vargas AI, Kapreli E, Bilika P, Polli A, Leysen L, Elma O, Roose E, Rheel E, Yilmaz ST, De Baets L, Huysmans E, Turk A, Saracoglu I. Towards precision pain medicine for pain after cancer: the Cancer Pain Phenotyping Network multidisciplinary international guidelines for pain phenotyping using nociplastic pain criteria. Br J Anaesth. 2023;130(5):611–21.

Neuropathic cancer pain is one of the most common complaints reported by cancer patients, with a frequency of 30-50% among those undergoing treatment, increasing to 70-90% as the disease progresses

Crofford, L.J. Chronic Pain: Where the Body Meets the Brain. Trans. Am. Clin. Climatol. Assoc. 2015, 126, 167–183. [PubMed]

Cleeland, C.S. Pain assessment in cancer. In Effect of Cancer on Quality of Life; CRC Press: Boca Raton, FL, USA, 2021; pp. 293–305. [Google Scholar]

Aninditha T., et al.Buku Ajar Neurologi Edisi Kedua Volume 2. Departement Neurologi Fakultas Kedokteran Universitas Indonesia Rumah Sakit Cipto Mangunkusumo, Jakarta, Yayasan Otak Sehat Indonesia. 2022.

Budisulistyo T, Sofyan HR. Nyeri kanker. Dalam: Aninditha T, Andriani R, Malueka RG, editors. Buku Ajar Neuroonkologi. Jakarta: Penerbit Kedokteran Indonesia; 2019. h. 314-37.

Korean J Intern Med. 2018;33(6):1058-1069. Publication date (electronic) : 2018 June 25. doi : https://doi.org/10.3904/kjim.2018.162

Bennett MI, Rayment C, Hjermstad M, Aass N, Caraceni A, Kaasa S. Prevalence and aetiology of neuropathic pain in cancer patients: a systematic review. Pain 2012;153:359-365.

Nicholson B. Differential diagnosis: nociceptive and neuro- pathic pain. Am J Manag Care 2006;12(9 Suppl):S256-S262.

World Health Organization., 2019. WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents

Yoon SY, Oh J. Neuropathic cancer pain: prevalence, pathophysiology, and management. Korean J Intern Med. 2018 Nov;33(6):1058-1069. doi: 10.3904/kjim.2018.162. Epub 2018 Jun 25. PMID: 29929349; PMCID: PMC6234399.

Li, Shuzhai MBa; Peng, Shixuan MBb; Chen, Fuchun MDc; Zeng, Bin MDa; Zhang, Zhen MDa; Zhang, Zhiming MD PhDa. The application and therapeutic effect of botulinum toxin type a (BTX-A) in the treatment of patients with pain after cancer treatment: a systematic review and meta-analysis. International Journal of Surgery 110(2):p 1215-1223, February 2024. | DOI: 10.1097/JS9.0000000000000916

Hong, B.; Yao, L.; Ni, L.; Wang, L.; Hu, X. Antinociceptive effect of botulinum toxin A involves alterations in AMPA receptor expression and glutamate release in spinal dorsal horn neurons. Neuroscience 2017, 357, 197–207. [Google Scholar] [CrossRef] [PubMed]

Datta Gupta, A.; Edwards, S.; Smith, J.; Snow, J.; Visvanathan, R.; Tucker, G.; Wilson, D. A Systematic Review and Meta-Analysis of Efficacy of Botulinum Toxin A for Neuropathic Pain. Toxins 2022, 14, 36. https://doi.org/10.3390/ toxins14010036.

Matak, I.; Bölcskei, K.; Bach-Rojecky, L.; Helyes, Z. Mechanisms of Botulinum Toxin Type A Action on Pain. Toxins 2019, 11, 459. https://doi.org/10.3390/toxins11080459

Teymoortash, A.; Pfestroff, A.; Wittig, A.; Franke, N.; Hoch, S.; Harnisch, S.; Schade-Brittinger, C.; Hoeffken, H.; Engenhart-Cabillic, R.; Brugger, M.; et al. Safety and Efficacy of Botulinum Toxin to Preserve Gland Function after Radiotherapy in Patients with Head and Neck Cancer: A Prospective, Randomized, Placebo-Controlled, Double-Blinded Phase I Clinical Trial. PLoS ONE 2016, 11, e0151316. [Google Scholar] [CrossRef]

Oh, H.-M.; Chung, M.E. Botulinum Toxin for Neuropathic Pain: A Review of the Literature. Toxins 2015, 7, 3127-3154. https://doi.org/10.3390/toxins7083127

Rostami, R.; Mittal, S.O.; Radmand, R.; Jabbari, B. Incobotulinum toxin-A improves post-surgical and post-radiation pain in cancer patients. Toxins 2016, 8, 22. [Google Scholar] [CrossRef] [PubMed]

De Groef, A.; Devoogdt, N.; Van Kampen, M.; Nevelsteen, I.; Smeets, A.; Neven, P.; Geraerts, I.; Dams, L.; Van der Gucht, E.; Debeer, P. Effectiveness of Botulinum Toxin A for Persistent Upper Limb Pain After Breast Cancer Treatment: A Double-Blinded Randomized Controlled Trial. Arch. Phys. Med. Rehabil. 2018, 99, 1342–1351. [Google Scholar] [CrossRef]

De Groef, A.; Devoogdt, N.; Van Kampen, M.; De Hertogh, L.; Vergote, M.; Geraerts, I.; Dams, L.; Van der Gucht, E.; Debeer, P. The effectiveness of Botulinum Toxin A for treatment of upper limb impairments and dysfunctions in breast cancer survivors: A randomised controlled trial. Eur. J. Cancer Care 2020, 29, e13175. [Google Scholar] [CrossRef]

Gabriel, A.; Champaneria, M.C.; Maxwell, G.P. The efficacy of botulinum toxin A in post-mastectomy breast reconstruction: A pilot study. Aesthetic Surg. J. 2015, 35, 402–409. [Google Scholar] [CrossRef]

Kim, S.I.; Choi, Y. Botulinum toxin injection for intractable pain in cancer patients with psoas muscle invasion. J. Pain Symptom Manag. 2022, 63, e441–e444. [CrossRef] [PubMed]

Lippi, L.; de Sire, A.; Turco, A.; Ferrillo, M.; Kesikburun, S.; Baricich, A.; Carda, S.; Invernizzi, M. Botulinum Toxin for Pain Relief in Cancer Patients: A Systematic Review of Randomized Controlled Trials. Toxins 2024, 16, 153. https://doi.org/10.3390/toxins16030153

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Published

2026-04-15

How to Cite

Christy, and Alvionita Muntholib. 2026. “BOTULINUM TOXIN TYPE A (BoNT-A) FOR NEUROPATIC CANCER PAIN : A SYSTEMATIC REVIEW”. The International Journal of Medical Science and Health Research 42 (2): 1-15. https://doi.org/10.70070/6977z217.