The Efficacy and Safety of Botulinum Neurotoxin Type A in Treating Chronic Low Back Pain: A Systematic Review, Meta-Analysis, Trial Sequential Analysis, and Meta-Regression

Waseem Wagrees¹, Hesham Kelani², Hazem Mohamed Salamah³, Abdelrahman Mahmoud⁴, Yehya Khlidj⁵, Mohamed R Abdelraouf⁶, Bahaa Sharaf⁷, Moustafa Elnewishy⁸, Nadia Albaramony⁹, Ahmed Naeem¹⁰, Ahmed Abd Elazim¹¹, Mohammad El-Ghanem¹², Diana Greene-Chandos¹³, Mohammad Jadidi², David P Lerner², Arthur D Kay², Lisa R Merlin^{2

14

15}, Charles Brock¹⁶

Affiliations

¹ Department of Neurology, School of Medicine, University of New Mexico, Albuquerque, New Mexico, USA.
² Department of Neurology, SUNY Downstate Health Sciences University at One Brooklyn Health, Brooklyn, New York, USA.
³ Faculty of Medicine, Zagazig University, Zagazig, Egypt.
⁴ Faculty of Medicine, Minia University, Minia, Egypt.
⁵ Faculty of Medicine, University of Algiers, Algiers, Algeria.
⁶ Faculty of Medicine, Alexandria University, Alexandria, Egypt.
⁷ Faculty of Molecular Biotechnology, Helwan University, Helwan, Egypt.
⁸ Faculty of Medicine, Cairo University, Cairo, Egypt.
⁹ Faculty of Medicine, Mansoura University, Mansoura, Egypt.
¹⁰ Al-Azhar Faculty of Medicine, Asyut, Egypt.
¹¹ Department of Neurology, University of South Dakota Sanford Medical Center, Sioux Falls, South Dakota, USA.
¹² Department of Clinical Science, HCA Houston-Northwest Medical Center, University of Houston, Houston, Texas, USA.
¹³ Department of Neurology, School of Medicine, University of Saint Louis, Saint Louis, Missouri, USA.
¹⁴ Department of Neurology, SUNY Downstate Health Sciences University, Brooklyn, New York, USA.
¹⁵ Department of Physiology and Pharmacology, SUNY Downstate Health Sciences University, Brooklyn, New York, USA.
¹⁶ Department of Neurology, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.

PMID: 39985117
DOI: 10.1002/ejp.4796

Meta-Analysis

The Efficacy and Safety of Botulinum Neurotoxin Type A in Treating Chronic Low Back Pain: A Systematic Review, Meta-Analysis, Trial Sequential Analysis, and Meta-Regression

Waseem Wagrees et al. Eur J Pain. 2025 Apr.

. 2025 Apr;29(4):e4796.

doi: 10.1002/ejp.4796.

Authors

Affiliations

¹ Department of Neurology, School of Medicine, University of New Mexico, Albuquerque, New Mexico, USA.
² Department of Neurology, SUNY Downstate Health Sciences University at One Brooklyn Health, Brooklyn, New York, USA.
³ Faculty of Medicine, Zagazig University, Zagazig, Egypt.
⁴ Faculty of Medicine, Minia University, Minia, Egypt.
⁵ Faculty of Medicine, University of Algiers, Algiers, Algeria.
⁶ Faculty of Medicine, Alexandria University, Alexandria, Egypt.
⁷ Faculty of Molecular Biotechnology, Helwan University, Helwan, Egypt.
⁸ Faculty of Medicine, Cairo University, Cairo, Egypt.
⁹ Faculty of Medicine, Mansoura University, Mansoura, Egypt.
¹⁰ Al-Azhar Faculty of Medicine, Asyut, Egypt.
¹¹ Department of Neurology, University of South Dakota Sanford Medical Center, Sioux Falls, South Dakota, USA.
¹² Department of Clinical Science, HCA Houston-Northwest Medical Center, University of Houston, Houston, Texas, USA.
¹³ Department of Neurology, School of Medicine, University of Saint Louis, Saint Louis, Missouri, USA.
¹⁴ Department of Neurology, SUNY Downstate Health Sciences University, Brooklyn, New York, USA.
¹⁵ Department of Physiology and Pharmacology, SUNY Downstate Health Sciences University, Brooklyn, New York, USA.
¹⁶ Department of Neurology, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.

PMID: 39985117
DOI: 10.1002/ejp.4796

Abstract

Background: Chronic low back pain (CLBP) is a leading cause of disability. Botulinum neurotoxin type A (BoNT-A) has strong anti-spasmodic and analgesic effects, suggesting that its local muscular injection can reduce CLBP compared to other therapies. In this systematic review and meta-analysis, we investigated the efficacy and safety of BoNT-A on patients with CLBP.

Methods: We searched PubMed, Scopus, Cochrane, and Web of Science databases for studies comparing BoNT-A to other therapies in terms of functional improvement and pain improvement as measured by visual analog scale (VAS) and clinically significant improvement in pain (50% or greater reduction in VAS score). We employed trial sequential analysis (TSA) to confirm the findings. The GRADE approach was employed to assess the overall quality of the evidence.

Results: The search yielded nine studies, seven randomised clinical trials (RCTs), and two prospective observational studies. Compared to the control, BoNT-A increased the incidence of clinically significant improvement in pain (RR = 4.82, 95% CI (3.00, 7.76), p < 0.00001) and functional improvement (RR = 3.81, 95% CI (2.40, 6.04), p < 0.00001) (low-certainty evidence), and reduced VAS score (MD = -1.62, 95% CI (-3.13, -0.11), p = 0.04) (very low-certainty evidence). Subgroup analysis showed that BoNT-A is effective against normal saline (moderate-certainty evidence), and it was comparable to steroids and local anaesthetics (very low-certainty evidence). TSA confirmed the findings regarding clinical improvement in pain and functional improvement.

Conclusion: BoNT-A is a tolerable and effective treatment for CLBP with a longer duration of action. Future high-quality studies are needed to confirm our findings.

Significance: This paper provides good evidence that BoNT-A may be employed in patients suffering from resistant chronic low back pain not responding to normal saline injection due to its higher efficacy and longer duration of action. Compared to steroids and local anaesthetics injections, there is not enough data to draw a firm conclusion and future studies are needed.

Keywords: BoNT‐A; back pain; botulinum neurotoxin; chronic pain; meta‐analysis.

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References

1. Adler, M., S. Pellett, S. K. Sharma, F. J. Lebeda, Z. F. Dembek, and M. A. Mahan. 2022. “Preclinical Evidence for the Role of Botulinum Neurotoxin A (BoNT/A) in the Treatment of Peripheral Nerve Injury.” Microorganisms 10: 886.
1. Aguayo‐Albasini, J. L., B. Flores‐Pastor, and V. Soria‐Aledo. 2014. “GRADE System: Classification of Quality of Evidence and Strength of Recommendation.” Cirugía Española English Ed 92: 82–88.
1. Alam, M., A. Geisler, D. Sadhwani, et al. 2015. “Effect of Needle Size on Pain Perception in Patients Treated With Botulinum Toxin Type A Injections.” JAMA Dermatology 151: 1194.
1. Battista, S., L. Buzzatti, M. Gandolfi, et al. 2021. “The Use of Botulinum Toxin A as an Adjunctive Therapy in the Management of Chronic Musculoskeletal Pain: A Systematic Review With Meta‐Analysis.” Toxins (Basel) 13, no. 9: 640. https://doi.org/10.3390/toxins13090640.
1. Begg, C. B., and M. Mazumdar. 1994. “Operating Characteristics of a Rank Correlation Test for Publication Bias.” Biometrics 50: 1088–1101.

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The Efficacy and Safety of Botulinum Neurotoxin Type A in Treating Chronic Low Back Pain: A Systematic Review, Meta-Analysis, Trial Sequential Analysis, and Meta-Regression

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The Efficacy and Safety of Botulinum Neurotoxin Type A in Treating Chronic Low Back Pain: A Systematic Review, Meta-Analysis, Trial Sequential Analysis, and Meta-Regression

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Abstract

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