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The efficacy of botulinum toxin type A in managing chronic musculoskeletal pain: a systematic review and meta analysis

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Abstract

Background

Botulinum toxin type A (BoNTA) is a neurotoxin that acts by inhibiting the release of neurotransmitters acetylcholine at neuromuscular junctions, thus reducing muscular contractions. Recent evidence suggests that BoNTA can reduce nociceptive activities of sensory neurons in animal models by inhibiting release of certain neuropeptides. Despite the therapeutic benefit of BoNTA in alleviating painful muscle spasms, its efficacy in other musculoskeletal pain conditions is less clear.

Objective

We aim to examine the efficacy of BoNTA in reducing chronic musculoskeletal pain.

Methods

Studies for inclusion in our report were identified using MEDLINE, EMBASE, PUBMED, Cochrane Central Register of Controlled Trials, CINAHL, and reference lists of relevant articles. Studies were considered eligible for inclusion if they were randomized controlled trials (RCTs), evaluating the efficacy of BoNTA injections in pain reduction. All studies were assessed and data were abstracted independently by paired reviewers. The outcome measures were baseline and final pain scores as assessed by the patients. The internal validity of trials was assessed with the Jadad scale. Disagreements were resolved through discussions.

Main results

Twenty-one studies were included in the systematic review and 15 of them were included in the final meta-analysis. There was a total of 706 patients in the meta-analysis, represented from trials of plantar fasciitis (n = 1), tennis elbow (n = 2), shoulder pain (n = 1), whiplash (n = 3), and myofascial pain (n = 8). Overall, there was a small to moderate pain reduction among BoNTA patients when compared to control (SMD = −0.27, 95% CI: −0.44 to −0.11). When the results were analyzed in subgroups, only tennis elbow (SMD = −0.44, 95% CI: −0.86 to −0.01) and plantar fasciitis (SMD = −1.04, 95% CI: −1.68 to −0.40) demonstrated significant pain relief. Although not in the meta-analysis, one back pain study also demonstrated positive results for BoNTA. Lastly, BoNTA was effective when used at ≥25 units per anatomical site or after a period ≥5 weeks.

Conclusion

In our meta-analysis, BoNTA had a small to moderate analgesic effect in chronic musculoskeletal pain conditions. It was particularly effective in plantar fasciitis, tennis elbow, and back pain, but not in whiplash or shoulder pain patients. However, more evidence is required before definitive conclusions can be drawn. On the other hand, there is convincing evidence that BoNTA lacks strong analgesic effects in patients with myofascial pain syndrome. A general dose-dependent and temporal response with BoNTA injections was also observed.

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References

  • Aoki RK (2003) Evidence for antinociceptive activity of botulinum toxin type A in pain management. Headache 43(Suppl 1):S9–S15

    Article  PubMed  Google Scholar 

  • Babcock MS, Foster L, Pasquina P, Jabbari B (2005) Treatment of pain attributed to plantar fasciitis with botulinum toxin A. Am J Phys Med Rebabil 84(9):649–654

    Article  Google Scholar 

  • Borg-Stein J, Simons DG (2002) Focused review: myofascial pain. Arch Phys Med Rehabil 83(3 suppl 1):S40–S49

    Article  PubMed  Google Scholar 

  • Borodic GE, Acquadro M, Johnson EA (2001) Botulinum toxin therapy for pain and inflammatory disorders: mechanisms and therapeutic effects. Expert Opin Investig Drugs 10:1531–1544

    Article  CAS  PubMed  Google Scholar 

  • Braker C, Yariv S, Adler R, Badarny S, Eisenberg E (2008) The analgesic effect of botulinum-toxin A on post-whiplash neck pain. Clin J Pain 24(1):5–10

    Article  PubMed  Google Scholar 

  • Carroll A, Barnes M, Comiskey C (2008) A prospective randomized controlled study of the role of botulinum toxin in whiplash-associated disorder. Clin Rehabil 22:513–519

    Article  PubMed  Google Scholar 

  • Charles PD (2004) Botulinum neurotoxin serotype A: a clinical update on non-cosmetic uses. Am J Health Syst Pharm 61(Suppl 6):S11–S23

    CAS  PubMed  Google Scholar 

  • Cheshire WP, Abashian SW, Mann DJ (1994) Botulinum toxin in the treatment of myofascial pain syndrome. Pain 59:65–69

    Article  CAS  PubMed  Google Scholar 

  • Cohen J (1988) Statistical Power Analysis in the Behavioral Sciences, 2nd edn Lawrence Erlbaum Associates, Inc., Hillsdale (NJ)

    Google Scholar 

  • Compendium of Pharmaceuticals and Specialties (2010) Webcom inc, Toronto 407 –410, Online http://www.e-cps.ca

  • Cui M, Khanijou S, Rubino J, Aoki KR (2004) Subcutaneous administration of Botulinum toxin A reduces formalin-induced pain. Pain 107:125–133

    Article  CAS  PubMed  Google Scholar 

  • De Andrés J, Cerda-Olmedo G, Valía JC, Monsalve V, Lopez-Alarcon MinguezA (2003) Use of botulinum toxin in the treatment of chronic myofascial pain. Clin J Pain 19(4):269–275

    Article  PubMed  Google Scholar 

  • DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  CAS  PubMed  Google Scholar 

  • Eccleston C, Crombez G, Aldrich S, Stannard C (1997) Attention and somatic awareness in chronic pain. Pain 72:209–215

    Article  CAS  PubMed  Google Scholar 

  • Esenyel M, Aldemir T, Gursoy E, Esenyel CZ, Demir S, Durmusoglu G (2007) Myofascial pain syndrome: efficacy of different therapies. J Back Musculoskelet Rehabil 20:43–47

    Google Scholar 

  • Ferrante FM, Bearn L, Rothrock R, King L (2005) Evidence against trigger point injection technique for the treatment of cervicothoracic myofascial pain with botulinum toxin type A. Anaesthesiology 103(2):377–383

    Article  CAS  Google Scholar 

  • Flanders M, Tischler A, Wise J, Williams F, Beneish R, Auger N (1987) Injection of type A botulinum toxin into extraocular muscles for correction of strabismus. Can J Ophtalmol 22(4):212–217

    CAS  Google Scholar 

  • Foster L, Clapp L, Erickson M, Jabbari B (2001) Botulinum toxin A and chronic low back pain. Neurology 56:1290–1293

    CAS  PubMed  Google Scholar 

  • Francisco GE (2004) Botulinum toxin: dosing and dilution. Am J Phys Med Rehabil 83(suppl):S30–S37

    Article  PubMed  Google Scholar 

  • Gobel H, Heinze A, Reichel G, Hefter H, Benecke R (2006) Efficacy and safety of a single botulinum type A toxin complex treatment (Dysport) for the relief of upper back myofascial pain syndrome: results from a randomized double-blind placebo-controlled multicentre study. Pain 125(1–2):82–88

    Article  PubMed  Google Scholar 

  • Guarda-Nardini L, Manfredini D, Salamone M, Salmaso L, Tonello S, Ferronato G (2008) Efficacy of botulinum toxin in treating myofascial pain in bruxers: a controlled placebo pilot study. J Craniomandibular Pract 26(2):126–135

    Google Scholar 

  • Hallett M (1999) One man’s position: clinical applications of botulinum toxin. N Engl J Med 341:118–120

    Article  CAS  PubMed  Google Scholar 

  • Hayton MJ, Santini AJA, Hughes PJ, Frostick SP, Trail IA, Stanley JK (2005) Botulinum toxin injection in the treatment of tennis elbow: A double blind, randomized, controlled, pilot study. J Bone Joint Surg Am 87:503–507

    Article  CAS  PubMed  Google Scholar 

  • Herr KA, Mobily PR, Smith C (1993) Depression and the experience of chronic back pain: a study of related variables and age differences. Clin J Pain 9:104–114

    Article  CAS  PubMed  Google Scholar 

  • Jabbari B (2007) Treatment of chronic low back pain with botulinum neurotoxins. Curr Pain Headache Rep 11(5):352–358

    Article  PubMed  Google Scholar 

  • Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomised controlled trials: is blinding necessary? Control Clin Trials 17:1–12

    Article  CAS  PubMed  Google Scholar 

  • Kamanli A, Kaya A, Ardicoglu O, Ozgocmen S, Zengin FO, Bayik Y (2005) Comparison of lidocaine injection, botulinum toxin injection, and dry needling to trigger points in myofascial pain syndrome. Rheumatol Int 25(8):604–611

    Article  CAS  PubMed  Google Scholar 

  • Kurtoglu C, Gur OH, Kurkcu M, Sertdemir Y, Guler-Uysal F, Uysal H (2008) Effect of botulinum toxin A in myofascial pain patients with or without functional disc displacement. J Oral Maxillofac Surg 66:1644–1651

    Article  PubMed  Google Scholar 

  • Lang AM (2000) A pilot study of botulinum toxin type A (Botox), administered using a novel injection technique, for the treatment of myofascial pain. Am J Pain Manag 10:108–112

    Google Scholar 

  • Lang AM (2003) Botulinum toxin type A therapy in chronic pain disorders. Arch Phys Med Rehabil 84(Suppl 1):S69–S73

    Article  PubMed  Google Scholar 

  • Lew MF (2002) Review of the FDA-approved uses of botulinum toxins, including data suggesting efficacy in pain reduction. Clin J Pain 18:S142–S146

    Article  PubMed  Google Scholar 

  • Lew HL, Lee EH, Castaneda A, Klima R, Date E (2008) Therapeutic use of botulinum toxin type A in treating neck and upper-back pain of myofascial origin: A pilot study. Arch Phys Med Rehabil 89(1):75–80

    Article  PubMed  Google Scholar 

  • Magni G, Caldieron C, Rigatti-Luchini S et al (1990) Chronic musculoskeletal pain and depressive symptoms in the general population: an analysis of the 1st national health and nutrition examination survey data. Pain 43:299–307

    Article  CAS  PubMed  Google Scholar 

  • National Institute of Health (1998) NIH Guide: new directions in pain research I. Sept 4, available from http://www.grants.nih.gov/grants/guide/pa-files/PA-98-102.html

  • Naumann M, So Y, Argoff CE, Childers MK, Dykstra DD, Gronseth GS, Kaufmann HC, Schurch B, Silberstein SD, Simpson DM (2008) Assessment: botuinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review). Neurology 70:1707–1714

    Article  CAS  PubMed  Google Scholar 

  • Nixdorf DR, Heo G, Major PW (2002) Randomized controlled trial of botulinum toxin A for chronic myogenous orofacial pain. Pain 99:465–473

    Article  CAS  PubMed  Google Scholar 

  • Odergrena T, Hjaltasona H, Kaakkolab H, Soldersc G, Hankod J, Fehlingd C, Marttilae RJ, Lundhf H, Geding S, Westergreng I, Richardsonh A, Dotth C, Cohenh H (1998) A double blind, randomised, parallel group study to investigate the dose equivalence of Dysport® and Botox® in the treatment of cervical dystonia. J Neurol Neurosurg Psychiatr 64:6–12

    Article  Google Scholar 

  • Ojala T, Arokoski JPA, Partanen J (2006) The effect of small doses of botulinum toxin A on neck-shoulder myofascial pain syndrome: a double-blind, randomized, and controlled crossover trial. Clin J Pain 22:90–96

    Article  PubMed  Google Scholar 

  • Padberg M, de Bruijn SFTM, Tavy DLJ (2007) Neck pain in chronic whiplash syndrome treated with botulinum toxin. A double-blind, placebo-controlled clinical trial. J Neurol 254:290–295

    Article  CAS  PubMed  Google Scholar 

  • Placzeck R, Drescher W, Deuretzbacher G, Hempfing A, Meiss L (2007) Treatment of chronic radial epicondylitis with botulinum toxin A. A double-blind, placebo-controlled, randomized multicenter study. J Bone Joint Surg Am 89:255–260

    Article  Google Scholar 

  • Porta M (1999) Botulinum toxin type A injections for myofascial pain syndrome and tension-type headache. Eur J Neurol 6(S4):s103–s109

    Article  Google Scholar 

  • Qerama E, Fuglsang-Frederiksen A, Kasch H, Bach FW, Jensen TS (2006) A double-blind, controlled study of botulinum toxin A in chronic myofascial pain. Neurology 67:241–245

    Article  CAS  PubMed  Google Scholar 

  • Review Manager (RevMan) (2008) (Computer program). Version 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration

  • Royal MA, Gunyea I, Bhakta B, Movva V, Ward S, Jenson M (2001) Botulinum toxin type A in the treatment of refractory myofascial pain (abstract). Neurology 56(Suppl 3):A350

    Google Scholar 

  • Simons DG, Travell JG, Simons LS (1999) Myofascial pain and dysfunction: The trigger point manual. 2nd edn. Upper half of body, vol. 1, Williams & Wilkins, Baltimore (MD)

    Google Scholar 

  • Singh G, Triadafilopoulos G (1999) Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol 26(Suppl 56):18–24

    Google Scholar 

  • Singh JA, Mahowald ML, Noorbaloochi S (2009) Intra-articular botulinum toxin A for refractory shoulder pain: a randomized, double-blinded, placebo-controlled trial. Transl Res 153:205–221

    Article  CAS  PubMed  Google Scholar 

  • Sohling M (2002) Treatment of myofascial pain of the shoulder and neck region with botulinum toxin A. Naunyn-Schmiedeberg’s Arch Pharmacol 365(2):R42

    Google Scholar 

  • Szczepanska-Szerej A, Stepniak C, Szczepanski L (2003) Clinical evaluation of botulinum toxin A in the treatment of pain in patients with fibromyalgia. Reumatologia 41(4):335–340

    Google Scholar 

  • Tuzun EH (2007) Quality of life in chronic musculoskeletal pain. Best Pract Res Clin Rheumatol 21:567–579

    Article  PubMed  Google Scholar 

  • Wheeler AH, Goolkasian P (2001a) Open label assessment of botulinum toxin A for pain treatment in a private outpatient setting. J Musculoskeletal Pain 9:67–82

    Article  Google Scholar 

  • Wheeler AH, Goolkasian P, Gretz SS (1998) A randomized, double-blind, prospective pilot study of botulinum toxin injection for refractory, unilateral, cervicothoracic, paraspinal, myofascial pain syndrome. Spine 23(15):1662–1666

    Article  CAS  PubMed  Google Scholar 

  • Wheeler AH, Goolkasian P, Gretz SS (2001b) Botulinum toxin A for the treatment of chronic neck pain. Pain 94:255–260

    Article  CAS  PubMed  Google Scholar 

  • Wiebe N, Vandermeer B, Platt RW, Klassen TP, Moher D, Barrowman NJ (2006) A systematic review identifies a lack of standardization in methods for handling missing variance data. J Clin Epidemiol 59:342–353

    Article  PubMed  Google Scholar 

  • Wohlfarth K, Sycha T, Ranoux D, Naver H, Caird D (2009) Dose equivalence of two commercial preparations of botulinum neurotoxin type A: time for a reassessment? Curr Med Res Opin 25(7):1573–1584

    Article  CAS  PubMed  Google Scholar 

  • Wong SM, Hul ACF, Tong P, Poon DWF, Yu E, Wong LKS (2005) Treatment of lateral epicondylitis with botulinum toxin. Ann Intern Med 143:793–797

    CAS  PubMed  Google Scholar 

  • Woolf AD, Pfleger B (2003) Burden of major musculoskeletal conditions. Bull World Health Organ 81:646–656

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada

    Tony Zhang

  2. Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada

    Tony Zhang, Aleem Adatia, Wasifa Zarin, Misha Moitri & Abi Vijenthira

  3. Division of Rheumatology, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada

    Walter Kean

  4. Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada

    Rong Chu & Lehana Thabane

  5. Biostatistics Unit, Father Sean O’Sullivan Research Centre, St. Joseph’s Healthcare, Hamilton, ON, Canada

    Rong Chu & Lehana Thabane

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  1. Tony Zhang
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  2. Aleem Adatia
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Correspondence to Walter Kean.

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Zhang, T., Adatia, A., Zarin, W. et al. The efficacy of botulinum toxin type A in managing chronic musculoskeletal pain: a systematic review and meta analysis. Inflammopharmacol 19, 21–34 (2011). https://doi.org/10.1007/s10787-010-0069-x

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