Botulinum Toxin Injection for Pain in Muscle Spasm and Visceromotor Disorders: A Meta-Analytic Study

Abstract

Background Apart from the popular use of botulinum neurotoxin type A (BoNT/A) for neuro-rehabilitation and cosmetic purposes, its analgesic potential has been highlighted in various studies. Although BoNT/A is effective, there is a paucity of literature explicating its effectiveness on muscle-based and visceromotor pain.

Objective This meta-analysis determined the effectiveness of botulinum type A (BoNT-A) in treating muscle-based (nociceptive) and visceromotor pain.

Data Sources Studies were searched at PubMed, ScienceDirect, EBSCO Host, and Google Scholar. Unpublished literature was also searched through ProQuest Dissertations & Theses Database and ClinicalTrials.gov.

Review Methods Randomized controlled trials (RCTs) and experimental studies on the effect of botulinum toxin on muscle-based pain were included. An abstraction form was independently accomplished by two reviewers. The standardized mean difference was used as the effect measure using the random-effects model and computed with RevMan 5.3.

Results A total of 17 RCTs were included and analyzed. The standardized mean difference was –0.40 (95%CI: –0.67, –0.13), statistically favoring the BoNT-A group (z=2.94, p = 0.003). Findings also showed a signifi cantly (X2=66.56, p<0.00001) large heterogeneity I2=74%; T2=0.21). Subgroup analyses according to dose concentration and length of follow-up visits showed lower pain scores in the BoNT-A group with a dose less than 300 units (z=2.49, p = 0.01) and a follow-up period greater than 12 weeks (z=2.31, p = 0.02).

Conclusion BoNT-A injections are effective in treating muscle-based (nociceptive) and visceromotor pain disorders.

Keywords: Botulinum neurotoxin, BoNT-A, pain, muscle-based pain, visceromotor pain.

  1. Münchau, A., Bhatia, K.P. (2000). Uses of botulinum toxin injection in medicine today. British Medical Journal, 321: 161 – 5. 
  2. Jankovic, J. (2004). Botulinum toxin in clinical practice. J NeurolNeurosurg Psychiatry, 75: 951 – 957. doi: 10.1136/jnnp.2003.034702
  3. Matak, I., Lacković, Z. (2014). Botulinum toxin A, brain and pain. Progress in Neurobiology. 39 – 59. doi: 10.1016/j.pneurobio.2014.06.001
  4. Winner, P. Botulinum toxins in the treatment of migraine and tension-type headaches. Phys. Med. Rehabil. Clin. N. Am. 14, 885–899 (2003).
  5. Deepai, S., Thomson, A., (2008). Women’s Health 4 (2), 173 -181. Botulinum toxin for pelvic pain in women. doi: 10.2217/17455057.4.2.173
  6. Akiyama, Y., Nomiya, A, Niimi, A., Yamada, Y., Fujimura, T., Nakagawa, T., Fukuhara, H., Kume, H., Igawa, Y., and Homma, Y. (2015). Botulinum toxin type A injection for refractory interstitial cystitis: A randomized comparative study and predictors of treatment response. International Journal of Urology, 22 (9), 835 – 841. doi: 10.1111/iju.12833.
  7. Guarda-Nardini, L., Stecco, A., Stecco, C., Masiero, S., and Manfredini, D. (2012). Myofascial pain of the jaw muscles: comparison of short-term effectiveness of botulinum toxin injections and fascial manipulation technique. Cranio, 30 (2), 95–102.
  8. Kasyan, G. and Pushkar D. (2012). Randomized controlled trial for efficacy of botulinum toxin type a in treatment of patients suffering bladder pain syndrome/interstitial cystitis with Hunners’ lesions: Preliminary results. Journal of Urology, 187 (4): E335–E336
  9. Kuo, H.C. and Chancellor, M.B. (2009). Comparison of intravesicalbotulinum toxin type A injections plus hydrodistention with hydrodistention alone for the treatment of refractory interstitial cystitis/painful bladder syndrome. BJU International, 104 (5), 657 – 661. doi: 10.1111/j.1464-410X.2009.08495.x
  10. Kuo, H.C., Jiang, Y.H., Tsai, Y.C., and Kuo, Y.C. (2015). Intravesicalbotulinum toxin-A injections reduce bladder pain of interstitial cystitis/bladder pain syndrome refractory to conventional treatment – A prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial. Neurourology and Urodynamics, 35 (5), 609 – 614. doi: 10.1002/nau.22760
  11. Kwanchuay, P., Petchnumsin, T., Yiemsiri, P., Pasuk, N., Srikanok, W., and Hathaiareerug, C. (2015). Efficacy and safety of single botulinum toxin type a (Botox®) injection for relief of upper trapezius myofascial trigger point: a randomized, double-blind, placebo-controlled study. Journal of the Medical Association of Thailand, 98 (12), 1231 – 1236.
  12. Lim, J.Y., Koh, J.H., and Paik, N.J. (2008).  Intramuscular botulinum toxin-A reduces hemiplegic shoulder pain: a randomized, double-blind, comparative study versus intraarticular triamcinolone acetonide. Stroke, 39 (1), 126 – 131.
  13. Marco, E., Duarte, E., Vila, J., Tejero, M., Guillen, A., Boza, R., Escalada, F., and Espadaler, J.M. (2007). Is botulinum toxin type A effective in the treatment of spastic shoulder pain in patients after stroke? A double-blind randomized clinical trial. Journal of Rehabilitation Medicine, 39 (6), 440 – 447.
  14. Nixdorf, D.R., Heo, G., and Major, P.W. (2002). Randomized controlled trial of botulinum toxin A for chronic myogenousorofacial pain. Pain, 99 (3), 465–73.
  15. Rosales, R.L. et al. Botulinum toxin injection for hypertonicity of the upper extremity within 12 weeks after a stroke: a randomized controlled trial.  Neural Rehabilitation and Neural Repair 26 (7), 812 – 821 (2012).doi:10.1177/1545968311430824.
  16. Shaw, L., Rodgers, H., Price, C., van Wijck, F., Shackley, P., Steen, N., Barnes, M., Ford, G., and Graham, L. (2010). BoTULS: a multicentre randomized controlled trial to evaluate the clinical effectiveness and cost-effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A. Health Technology Assessment, 14 (26), 1 – 158. DOI: 10.3310/hta14260.
  17. Singh, J.A. and Fitzgeral, P.M. Botulinum toxin for shoulder pain. Cochrane Database of Systematic Reviews (2010).doi: 10.1002/14651858.CD008271.pub2
  18. Yelnik, A.P., Colle, F.M., Bonan, I.V., and Vicaut, E. (2007). Treatment of shoulder pain in spastic hemiplegia by reducing spasticity of the subscapular muscle: a randomised, double blind, placebo controlled study of botulinum toxin A. Journal of Neurology, Neurosurgery, and Psychiatry, 78 (8), 845 – 848. 
  19. Wheeler, A. and Smith, H.S. (2013). Botulinum toxins: Mechanisms of action, antinociception and clinical applications. Toxicology, 306, 124 – 146. http://dx.doi.org/10.1016/j.tox.2013.02.006.
  20. Brin, M. F. et al. Localized injections of botulinum toxin for the treatment of focal dystonia and hemifacial spasm. Mov. Disord. 2, 237–254 (1987).
  21. Binder, W. J. et al. Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study. Otolaryngol. Head Neck Surg. 123, 669–676 (2000).
  22. Dressler, D. (2013). Botulinum toxin therapy: its use for neurological disorders of the autonomic nervous system. Journal of Neurology, 701-713. doi: 10.1007/s00415-012-6615-2
  23. El-enen, M.A., Abou-Farha, M., El-Abd, A., El-Tatawy, H., Tawfik, A., El-Abd, S., Rashed, M., and El-sharaby, M. (2015). Intraprostatic injection of botulinum toxin-A in patients with refractory chronic pelvic pain syndrome: the transurethral vs. transrectal approach. Arab Journal of Urology, 13, 94 – 99.
  24. El-Khawand, D., Wehbe, S., Whitmore, S. (2013). Botulinum toxin for conditions of the female pelvis. IntUrogynecol J, (24), 1073 – 1081. doi: 10.1007/s00192-012-2035-1
  25. Lim, E.C.H., Seet, R. C. (2010). Use of botulinum toxin in the neurology clinic. Nature Reviews. Neurology.doi: 10.1038/nrneurol.2010.149
  26. Mahowald, M. L., Singh, J. A. & Dykstra, D. Long term effects of intra-articular botulinum toxin A for refractory joint pain. Neurotox. Res. 9, 179–188 (2006).
  27. Piovesan, E. J. et al. An open study of botulinum-A toxin treatment of trigeminal neuralgia. Neurology 65, 1306–1308 (2005).
  28. Popoff, M.R. and Bouvet, P. (2013). Genetic characteristics of toxigenic Clostridia and toxin gene evolution. Toxicon, 75, 63 – 89.
  29. Qerama, E. et al. A double-blind, controlled study of botulinum toxin A in chronic myofascial pain. Neurology 67, 241–245 (2006).
  30. Shackleton, T., Ram, S., Black, M., Ryder, J., Clark, G.T., and Enciso, R. (2016). The efficacy of botulinum toxin for the treatment of trigeminal and postherpetic neuralgia: a systematic review with meta-analyses. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 122 (1), 61 – 71. http://dx.doi.org/10.1016/j.oooo.2016.03.003.

Articles related to the one you are viewing

There are currently no results to show, please try again later

CC BY: Open Access Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/