Skip to main content
SpringerLink
Log in

Botulinum Toxins (BoNTs) for Treatment of Pain in Orthopedic Disorders

  • Chapter
  • First Online:
Botulinum Toxin Treatment of Pain Disorders

  • 390 Accesses

Abstract

Chronic pain is a major issue in many orthopedic disorders. With the discovery of analgesic effects of BoNTs, there is an emerging interest in exploring a potential role for BoNT injections in relieving orthopedic pain. In this chapter, the data on BoNT therapy in four orthopedic disorders are presented—with information on blinded studies provided in more detail. These disorders consist of chronic lateral epicondylitis, painful local arthritis, refractory pain after total knee arthroplasty, and anterior knee pain related to patellofemoral syndrome due to vastus lateralis imbalance.

The efficacy levels are defined based on recommendations of the Guideline and Assessment Subcommittee of the American Academy of Neurology. The level of evidence for chronic lateral epicondylitis is B (probably effective) based on one class I and two class II studies; it is level C (possibly effective) for refractory pain after total knee arthroplasty, local painful arthritis, and anterior knee pain related to vastus lateralis imbalance (each with one class II study). While these positive data are encouraging, better designed and more high-quality studies (class I and II) are needed to support the use of botulinum neurotoxin injections in these orthopedic disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Blanshan N, Krug H. The use of botulinum toxin for the treatment of chronic joint pain: clinical and experimental evidence. Toxins (Basel). 2020;12(5):314. https://doi.org/10.3390/toxins12050314. PMID: 32397671; PMCID: PMC7291335

    Article  CAS  Google Scholar 

  2. Hootman JM, Helmick CG, Barbour KE, Theis KA, Boring MA. Updated projected prevalence of self-reported doctor-diagnosed arthritis and arthritis-attributable activity limitation among US adults, 2015–2040. Arthritis Rheumatol. 2016;68:1582–7. https://doi.org/10.1002/art.39692.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Malfait AM, Schnitzer TJ. Towards a mechanism-based approach to pain management in osteoarthritis. Nat Rev Rheumatol. 2013;9:654–64. https://doi.org/10.1038/nrrheum.2013.138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Rossetto O, Pirazzini M, Fabris F, Montecucco C. Botulinum neurotoxins: mechanism of action. Handb Exp Pharmacol. 2021;263:35–47. https://doi.org/10.1007/164_2020_355. PMID: 32277300

    Article  CAS  PubMed  Google Scholar 

  5. Bach-Rojecky L, Relja M, Lacković Z. Botulinum toxin type A in experimental neuropathic pain. J Neural Transm (Vienna). 2005;112(2):215–9. https://doi.org/10.1007/s00702-004-0265-1. PMID: 15657640

    Article  CAS  Google Scholar 

  6. Matak I, Tékus V, Bölcskei K, Lacković Z, Helyes Z. Involvement of substance P in the antinociceptive effect of botulinum toxin type A: evidence from knockout mice. Neuroscience. 2017;358:137–45. https://doi.org/10.1016/j.neuroscience.2017.06.040. Epub 2017 Jul 1. PMID: 28673722

    Article  CAS  PubMed  Google Scholar 

  7. Marino MJ, Terashima T, Steinauer JJ, Eddinger KA, Yaksh TL, Xu Q. Botulinum toxin B in the sensory afferent: transmitter release, spinal activation, and pain behavior. Pain. 2014;155(4):674–84. https://doi.org/10.1016/j.pain.2013.12.009. Epub 2013 Dec 11. PMID: 24333775; PMCID: PMC3960322

    Article  CAS  PubMed  Google Scholar 

  8. Cui M, Khanijou S, Rubino J, Aoki KR. Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain. 2004;107(1–2):125–33. https://doi.org/10.1016/j.pain.2003.10.008. PMID: 14715398

    Article  CAS  PubMed  Google Scholar 

  9. Mika J, Rojewska E, Makuch W, Korostynski M, Luvisetto S, Marinelli S, Pavone F, Przewlocka B. The effect of botulinum neurotoxin A on sciatic nerve injury-induced neuroimmunological changes in rat dorsal root ganglia and spinal cord. Neuroscience. 2011;175:358–66. https://doi.org/10.1016/j.neuroscience.2010.11.040. Epub 2010 Nov 25. PMID: 21111791

    Article  CAS  PubMed  Google Scholar 

  10. Bossowska A, Lepiarczyk E, Mazur U, Janikiewicz P, Markiewicz W. Botulinum toxin type A induces changes in the chemical coding of substance P-immunoreactive dorsal root ganglia sensory neurons supplying the porcine urinary bladder. Toxins (Basel). 2015;7(11):4797–816. https://doi.org/10.3390/toxins7114797. PMID: 26580655; PMCID: PMC4663534

    Article  CAS  Google Scholar 

  11. Wang W, Kong M, Dou Y, Xue S, Liu Y, Zhang Y, Chen W, Li Y, Dai X, Meng J, Wang J. Selective expression of a SNARE-cleaving protease in peripheral sensory neurons attenuates pain-related gene transcription and neuropeptide release. Int J Mol Sci. 2021;22(16):8826. https://doi.org/10.3390/ijms22168826. PMID: 34445536; PMCID: PMC8396265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shin MC, Wakita M, Xie DJ, Yamaga T, Iwata S, Torii Y, Harakawa T, Ginnaga A, Kozaki S, Akaike N. Inhibition of membrane Na+ channels by A type botulinum toxin at femtomolar concentrations in central and peripheral neurons. J Pharmacol Sci. 2012;118(1):33–42. https://doi.org/10.1254/jphs.11060fp. Epub 2011 Dec 10. PMID: 22156364

    Article  CAS  PubMed  Google Scholar 

  13. 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. https://doi.org/10.1016/j.neuroscience.2017.06.004. Epub 2017 Jun 10. PMID: 28606856

    Article  CAS  PubMed  Google Scholar 

  14. Matak I, Bölcskei K, Bach-Rojecky L, Helyes Z. Mechanisms of botulinum toxin Type A action on pain. Toxins (Basel). 2019;11(8):459. https://doi.org/10.3390/toxins11080459. PMID: 31387301; PMCID: PMC6723487

    Article  CAS  PubMed Central  Google Scholar 

  15. Matak I, Riederer P, Lacković Z. Botulinum toxin’s axonal transport from periphery to the spinal cord. Neurochem Int. 2012;61(2):236–9. https://doi.org/10.1016/j.neuint.2012.05.001. Epub 2012 May 8. PMID: 22580329

    Article  CAS  PubMed  Google Scholar 

  16. Lacković Z. Botulinum toxin and pain. Handb Exp Pharmacol. 2021;263:251–64. https://doi.org/10.1007/164_2019_348. PMID: 32016565

    Article  CAS  PubMed  Google Scholar 

  17. Drinovac Vlah V, Filipović B, Bach-Rojecky L, Lacković Z. Role of central versus peripheral opioid system in antinociceptive and anti-inflammatory effect of botulinum toxin type A in trigeminal region. Eur J Pain. 2018;22(3):583–91. https://doi.org/10.1002/ejp.1146. Epub 2017 Nov 13. PMID: 29134730

    Article  CAS  PubMed  Google Scholar 

  18. Aurora SK, Winner P, Freeman MC, Spierings EL, Heiring JO, DeGryse RE, VanDenburgh AM, Nolan ME, Turkel CC. OnabotulinumtoxinA for treatment of chronic migraine: pooled analyses of the 56-week PREEMPT clinical program. Headache. 2011;51(9):1358–73. https://doi.org/10.1111/j.1526-4610.2011.01990.x. Epub 2011 Aug 29. PMID: 21883197

    Article  PubMed  Google Scholar 

  19. Silberstein SD, Blumenfeld AM, Cady RK, Turner IM, Lipton RB, Diener HC, Aurora SK, Sirimanne M, DeGryse RE, Turkel CC, Dodick DW. OnabotulinumtoxinA for treatment of chronic migraine: PREEMPT 24-week pooled subgroup analysis of patients who had acute headache medication overuse at baseline. J Neurol Sci. 2013;331(1–2):48–56. https://doi.org/10.1016/j.jns.2013.05.003. Epub 2013 Jun 19. PMID: 23790235

    Article  CAS  PubMed  Google Scholar 

  20. Yuan RY, Sheu JJ, Yu JM, Chen WT, Tseng IJ, Chang HH, Hu CJ. Botulinum toxin for diabetic neuropathic pain: a randomized double-blind crossover trial. Neurology. 2009;72(17):1473–8. https://doi.org/10.1212/01.wnl.0000345968.05959.cf. Epub 2009 Feb 25. PMID: 19246421

    Article  CAS  PubMed  Google Scholar 

  21. Xiao L, Mackey S, Hui H, Xong D, Zhang Q, Zhang D. Subcutaneous injection of botulinum toxin a is beneficial in postherpetic neuralgia. Pain Med. 2010;11(12):1827–33. https://doi.org/10.1111/j.1526-4637.2010.01003.x. PMID: 21134121

    Article  PubMed  Google Scholar 

  22. Childers MK, Wilson DJ, Gnatz SM, Conway RR, Sherman AK. Botulinum toxin type A use in piriformis muscle syndrome: a pilot study. Am J Phys Med Rehabil. 2002;81(10):751–9. https://doi.org/10.1097/00002060-200210000-00006. PMID: 12362115

    Article  PubMed  Google Scholar 

  23. Wu CJ, Lian YJ, Zheng YK, Zhang HF, Chen Y, Xie NC, Wang LJ. Botulinum toxin type A for the treatment of trigeminal neuralgia: results from a randomized, double-blind, placebo-controlled trial. Cephalalgia. 2012;32(6):443–50. https://doi.org/10.1177/0333102412441721. Epub 2012 Apr 5. PMID: 22492424

    Article  PubMed  Google Scholar 

  24. Han ZA, Song DH, Oh HM, Chung ME. Botulinum toxin type A for neuropathic pain in patients with spinal cord injury. Ann Neurol. 2016;79(4):569–78. https://doi.org/10.1002/ana.24605. Epub 2016 Feb 16. PMID: 26814620; PMCID: PMC4825405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ranoux D, Attal N, Morain F, Bouhassira D. Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol. 2008;64(3):274–83. https://doi.org/10.1002/ana.21427. Erratum in: Ann Neurol. 2009 Mar;65(3):359. PMID: 18546285

    Article  PubMed  Google Scholar 

  26. Akalin Ç, Yavuzarslan AB, Akyol C. Efficacy and safety of endoanal ultrasound-guided botulinum toxin in chronic anal fissure. Am Surg. 2021;27:31348211034750. https://doi.org/10.1177/00031348211034750. Epub ahead of print. PMID: 34313489

    Article  Google Scholar 

  27. Torkamand F, Mirjavadi SJ, Khatami F, Guitynavard F, Aghamir SMK. Evaluation of several botulinum toxins-A delivering systems into the bladder in interstitial cystitis/painful bladder syndrome (IC/PBS). Am J Clin Exp Urol. 2019;7(5):346–51. PMID: 31763366; PMCID: PMC6872472

    PubMed  PubMed Central  Google Scholar 

  28. Babcock MS, Foster L, Pasquina P, Jabbari B. Treatment of pain attributed to plantar fasciitis with botulinum toxin a: a short-term, randomized, placebo-controlled, double-blind study. Am J Phys Med Rehabil. 2005;84(9):649–54. https://doi.org/10.1097/01.phm.0000176339.73591.d7. PMID: 16141740

    Article  PubMed  Google Scholar 

  29. Safarpour Y, Jabbari B. Botulinum toxin treatment of pain syndromes - an evidence based review. Toxicon. 2018;147:120–8. https://doi.org/10.1016/j.toxicon.2018.01.017. Epub 2018 Feb 1. PMID: 29409817

    Article  CAS  PubMed  Google Scholar 

  30. Degen RM, Conti MS, Camp CL, Altchek DW, Dines JS, Werner BC. Epidemiology and disease burden of lateral epicondylitis in the USA: analysis of 85,318 patients. HSS J. 2018;14(1):9–14. https://doi.org/10.1007/s11420-017-9559-3. Epub 2017 Jun 5. PMID: 29398988; PMCID: PMC5786580

    Article  PubMed  Google Scholar 

  31. Hamilton PG. The prevalence of humeral epicondylitis: a survey in general practice. J R Coll Gen Pract. 1986;36(291):464–5. PMID: 3440991; PMCID: PMC1960610

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Verhaar JA. Tennis elbow. Anatomical, epidemiological and therapeutic aspects. Int Orthop. 1994;18(5):263–7. https://doi.org/10.1007/BF00180221. PMID: 7852001

    Article  CAS  PubMed  Google Scholar 

  33. Solheim E, Hegna J, Øyen J. Arthroscopic versus open tennis elbow release: 3- to 6-year results of a case-control series of 305 elbows. Arthroscopy. 2013;29(5):854–9. https://doi.org/10.1016/j.arthro.2012.12.012. Epub 2013 Feb 4. PMID: 23388420

    Article  PubMed  Google Scholar 

  34. Nirschl RP, Ashman ES. Elbow tendinopathy: tennis elbow. Clin Sports Med. 2003;22(4):813–36. https://doi.org/10.1016/s0278-5919(03)00051-6. PMID: 14560549

    Article  PubMed  Google Scholar 

  35. Connell D, Burke F, Coombes P, McNealy S, Freeman D, Pryde D, Hoy G. Sonographic examination of lateral epicondylitis. AJR Am J Roentgenol. 2001;176(3):777–82. https://doi.org/10.2214/ajr.176.3.1760777. PMID: 11222225

    Article  CAS  PubMed  Google Scholar 

  36. Linnanmäki L, Kanto K, Karjalainen T, Leppänen OV, Lehtinen J. Platelet-rich plasma or autologous blood do not reduce pain or improve function in patients with lateral epicondylitis: a randomized controlled trial. Clin Orthop Relat Res. 2020;478(8):1892–900. https://doi.org/10.1097/CORR.0000000000001185. PMID: 32732573; PMCID: PMC7371073

    Article  PubMed  PubMed Central  Google Scholar 

  37. Zhou Y, Guo Y, Zhou R, Wu P, Liang F, Yang Z. Effectiveness of acupuncture for lateral epicondylitis: a systematic review and meta-analysis of randomized controlled trials. Pain Res Manag. 2020;2020 Mar 20:8506591. https://doi.org/10.1155/2020/8506591. PMID: 32318130; PMCID: PMC7114772

    Article  Google Scholar 

  38. Yao G, Chen J, Duan Y, Chen X. Efficacy of extracorporeal shock wave therapy for lateral epicondylitis: a systematic review and meta-analysis. Biomed Res Int. 2020;2020:2064781. https://doi.org/10.1155/2020/2064781. PMID: 32309425; PMCID: PMC7106907

    Article  PubMed  PubMed Central  Google Scholar 

  39. Acosta-Olivo CA, Millán-Alanís JM, Simental-Mendía LE, Álvarez-Villalobos N, Vilchez-Cavazos F, Peña-Martínez VM, Simental-Mendía M. Effect of normal saline injections on lateral epicondylitis symptoms: a systematic review and meta-analysis of randomized clinical trials. Am J Sports Med. 2020;48(12):3094–102. https://doi.org/10.1177/0363546519899644. Epub 2020 Feb 11. PMID: 32045280

    Article  PubMed  Google Scholar 

  40. Krogh TP, Bartels EM, Ellingsen T, Stengaard-Pedersen K, Buchbinder R, Fredberg U, Bliddal H, Christensen R. Comparative effectiveness of injection therapies in lateral epicondylitis: a systematic review and network meta-analysis of randomized controlled trials. Am J Sports Med. 2013;41(6):1435–46. https://doi.org/10.1177/0363546512458237. Epub 2012 Sep 12. PMID: 22972856

    Article  PubMed  Google Scholar 

  41. Behazin M, Kachooei AR. Arthroscopic recession technique in the surgery of tennis elbow by sharp cutting the Extensor Carpi radialis Brevis (ECRB) tendon origin. Arch Bone Jt Surg. 2021;9(2):174–9. https://doi.org/10.22038/abjs.2020.48173.2383. PMID: 34026934; PMCID: PMC8121031

    Article  PubMed  PubMed Central  Google Scholar 

  42. Wong SM, Hui AC, Tong PY, Poon DW, Yu E, Wong LK. Treatment of lateral epicondylitis with botulinum toxin: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2005;143(11):793–7. https://doi.org/10.7326/0003-4819-143-11-200512060-00007. PMID: 16330790

    Article  CAS  PubMed  Google Scholar 

  43. Hayton MJ, Santini AJ, Hughes PJ, Frostick SP, Trail IA, Stanley JK. Botulinum toxin injection in the treatment of tennis elbow. A double-blind, randomized, controlled, pilot study. J Bone Joint Surg Am. 2005;87(3):503–7. https://doi.org/10.2106/JBJS.D.01896. PMID: 15741614

    Article  CAS  PubMed  Google Scholar 

  44. Placzek R, Drescher W, Deuretzbacher G, Hempfing A, Meiss AL. Treatment of chronic radial epicondylitis with botulinum toxin A. A double-blind, placebo-controlled, randomized multicenter study. J Bone Joint Surg Am. 2007;89(2):255–60. https://doi.org/10.2106/JBJS.F.00401. PMID: 17272437

    Article  PubMed  Google Scholar 

  45. Espandar R, Heidari P, Rasouli MR, Saadat S, Farzan M, Rostami M, Yazdanian S, Mortazavi SM. Use of anatomic measurement to guide injection of botulinum toxin for the management of chronic lateral epicondylitis: a randomized controlled trial. CMAJ. 2010;182(8):768–73. https://doi.org/10.1503/cmaj.090906. Epub 2010 Apr 26. PMID: 20421357; PMCID: PMC2871199

    Article  PubMed  PubMed Central  Google Scholar 

  46. Creuzé A, Petit H, de Sèze M. Short-term effect of low-dose, electromyography-guided botulinum toxin a injection in the treatment of chronic lateral epicondylar tendinopathy: a randomized, double-blinded study. J Bone Joint Surg Am. 2018;100(10):818–26. https://doi.org/10.2106/JBJS.17.00777. PMID: 29762276

    Article  PubMed  Google Scholar 

  47. Gronseth G, French J. Practice parameters and technology assessments: what they are, what they are not, and why you should care. Neurology. 2008;71(20):1639–43. https://doi.org/10.1212/01.wnl.0000336535.27773.c0. PMID: 19001255

    Article  PubMed  Google Scholar 

  48. French J, Gronseth G. Lost in a jungle of evidence: we need a compass. Neurology. 2008;71(20):1634–8. https://doi.org/10.1212/01.wnl.0000336533.19610.1b. PMID: 19001254

    Article  PubMed  Google Scholar 

  49. Lin YC, Tu YK, Chen SS, Lin IL, Chen SC, Guo HR. Comparison between botulinum toxin and corticosteroid injection in the treatment of acute and subacute tennis elbow: a prospective, randomized, double-blind, active drug-controlled pilot study. Am J Phys Med Rehabil. 2010;89(8):653–9. https://doi.org/10.1097/PHM.0b013e3181cf564d. PMID: 20134306

    Article  PubMed  Google Scholar 

  50. Guo YH, Kuan TS, Chen KL, Lien WC, Hsieh PC, Hsieh IC, Chiu SH, Lin YC. Comparison between steroid and 2 different sites of botulinum toxin injection in the treatment of lateral epicondylalgia: a randomized, double-blind, active drug-controlled pilot study. Arch Phys Med Rehabil. 2017;98(1):36–42. https://doi.org/10.1016/j.apmr.2016.08.475. Epub 2016 Sep 22. PMID: 27666156

    Article  PubMed  Google Scholar 

  51. Keizer SB, Rutten HP, Pilot P, Morré HH, v Os JJ, Verburg AD. Botulinum toxin injection versus surgical treatment for tennis elbow: a randomized pilot study. Clin Orthop Relat Res 2002;(401):125–131. https://doi.org/10.1097/00003086-200208000-00015. PMID: 12151889.

  52. Lee SH, Choi HH, Chang MC. The effect of botulinum toxin injection into the common extensor tendon in patients with chronic lateral epicondylitis: a randomized trial. Pain Med. 2020;21(9):1971–6. https://doi.org/10.1093/pm/pnz323. PMID: 31804698

    Article  PubMed  Google Scholar 

  53. Galván Ruiz A, Vergara Díaz G, Rendón Fernández B, Echevarría Ruiz De Vargas C. Effects of ultrasound-guided Administration of botulinum toxin (IncobotulinumtoxinA) in patients with lateral epicondylitis. Toxins (Basel). 2019;11(1):46. https://doi.org/10.3390/toxins11010046. PMID: 30650587; PMCID: PMC6356468

    Article  CAS  Google Scholar 

  54. Morré HH, Keizer SB, van Os JJ. Treatment of chronic tennis elbow with botulinum toxin. Lancet. 1997;349(9067):1746. https://doi.org/10.1016/s0140-6736(05)62958-3. PMID: 9193392

    Article  PubMed  Google Scholar 

  55. Lim EC, Seet RC, Cheah AE, Lim AY. Injection of botulinum toxin to the extensor carpi radialis brevis for tennis elbow. J Hand Surg Eur Vol. 2010;35(5):425–6. https://doi.org/10.1177/1753193409349844. PMID: 20515991

    Article  PubMed  Google Scholar 

  56. Song B, Day D, Jayaram P. Efficacy of botulinum toxin in treating lateral epicondylitis-does injection location matter?: a systematic review. Am J Phys Med Rehabil. 2020;99(12):1157–63. https://doi.org/10.1097/PHM.0000000000001511. PMID: 33214499

    Article  PubMed  Google Scholar 

  57. Dong W, Goost H, Lin XB, Burger C, Paul C, Wang ZL, Kong FL, Welle K, Jiang ZC, Kabir K. Injection therapies for lateral epicondylalgia: a systematic review and Bayesian network meta-analysis. Br J Sports Med. 2016;50(15):900–8. https://doi.org/10.1136/bjsports-2014-094387. Epub 2015 Sep 21. PMID: 26392595

    Article  PubMed  Google Scholar 

  58. Kim GM, Yoo SJ, Choi S, Park YG. Current trends for treating lateral epicondylitis. Clin Shoulder Elb. 2019;22(4):227–34. https://doi.org/10.5397/cise.2019.22.4.227. PMID: 33330224; PMCID: PMC7714311

    Article  PubMed  PubMed Central  Google Scholar 

  59. Grüner S, Schulz A, Schlüter-Brust K, Lippert-Grüner M. Botulinum toxin for chronic lateral epicondylitis (LE). Z Orthop Unfall. 2021;159(5):554–564. English, German. https://doi.org/10.1055/a-1202-6220. Epub 2020 Aug 3. PMID: 32746490.

  60. Quicke JG, Conaghan PG, Corp N, Peat G. Osteoarthritis year in review 2021: epidemiology & therapy. Osteoarthr Cartil. 2021:S1063–4584(21)00934–1. https://doi.org/10.1016/j.joca.2021.10.003. Epub ahead of print. PMID: 34695571.

  61. Cheng OT, Souzdalnitski D, Vrooman B, Cheng J. Evidence-based knee injections for the management of arthritis. Pain Med. 2012;13(6):740–53. https://doi.org/10.1111/j.1526-4637.2012.01394.x. Epub 2012 May 23. PMID: 22621287; PMCID: PMC3376243

    Article  PubMed  Google Scholar 

  62. Yurtbay A, Say F, Çinka H, Ersoy A. Multiple platelet-rich plasma injections are superior to single PRP injections or saline in osteoarthritis of the knee: the 2-year results of a randomized, double-blind, placebo-controlled clinical trial. Arch Orthop Trauma Surg. 2021; https://doi.org/10.1007/s00402-021-04230-2. Epub ahead of print. PMID: 34705072

  63. Bettonville M, Léon M, Margaux J, Urbin-Choffray D, Theunissen E, Besse-Hammer T, Fortems Y, Verlinden S, Godeaux O, Delmarcelle AS, Kaux JF. Safety and efficacy of a single intra-articular injection of a novel enhanced protein solution (JTA-004) compared to hylan G-F 20 in symptomatic knee osteoarthritis: a randomized, double-blind, controlled phase II/III study. BMC Musculoskelet Disord. 2021;22(1):888. https://doi.org/10.1186/s12891-021-04750-3. PMID: 34666767; PMCID: PMC8527807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Chen HH, Chen YC, Yu SN, Lai WL, Shen YS, Shen PC, Lin SH, Chang CH, Lee SM. Infrapatellar fat pad-derived mesenchymal stromal cell product for treatment of knee osteoarthritis: a first-in-human study with evaluation of the potency marker. Cytotherapy. 2021;22:1377. https://doi.org/10.1016/j.jcyt.2021.08.006. Epub ahead of print. PMID: 34696962

    Article  CAS  Google Scholar 

  65. Lee E, Padgett B. Intra-articular injection of BPC 157 for multiple types of knee pain. Altern Ther Health Med. 2021;27(4):8–13. PMID: 34324435

    PubMed  Google Scholar 

  66. Mahowald ML, Singh JA, Dykstra D. Long term effects of intra-articular botulinum toxin A for refractory joint pain. Neurotox Res. 2006;9(2–3):179–88. https://doi.org/10.1007/BF03033937. PMID: 16785116

    Article  CAS  PubMed  Google Scholar 

  67. Castiglione A, Bagnato S, Boccagni C, Romano MC, Galardi G. Efficacy of intra-articular injection of botulinum toxin type A in refractory hemiplegic shoulder pain. Arch Phys Med Rehabil. 2011;92(7):1034–7. https://doi.org/10.1016/j.apmr.2011.01.015. PMID: 21704782

    Article  PubMed  Google Scholar 

  68. McAlindon TE, Schmidt U, Bugarin D, Abrams S, Geib T, DeGryse RE, Kim K, Schnitzer TJ. Efficacy and safety of single-dose onabotulinumtoxinA in the treatment of symptoms of osteoarthritis of the knee: results of a placebo-controlled, double-blind study. Osteoarthr Cartil. 2018;26(10):1291–9. https://doi.org/10.1016/j.joca.2018.05.001. Epub 2018 May 9. PMID: 29753118

    Article  CAS  Google Scholar 

  69. Arendt-Nielsen L, Jiang GL, DeGryse R, Turkel CC. Intra-articular onabotulinumtoxinA in osteoarthritis knee pain: effect on human mechanistic pain biomarkers and clinical pain. Scand J Rheumatol. 2017;46(4):303–16. https://doi.org/10.1080/03009742.2016.1203988. Epub 2016 Oct 13. PMID: 27733091

    Article  CAS  PubMed  Google Scholar 

  70. Eleopra R, Rinaldo S, Lettieri C, Santamato A, Bortolotti P, Lentino C, Tamborino C, Causero A, Devigili G. AbobotulinumtoxinA: a new therapy for hip osteoarthritis. A prospective randomized double-blind multicenter study. Toxins (Basel). 2018;10(11):448. https://doi.org/10.3390/toxins10110448. PMID: 30384438; PMCID: PMC6266300

    Article  CAS  Google Scholar 

  71. Najafi S, Sanati E, Khademi M, Abdorrazaghi F, Mofrad RK, Rezasoltani Z. Intra-articular botulinum toxin type A for treatment of knee osteoarthritis: clinical trial. Toxicon. 2019;165:69–77. https://doi.org/10.1016/j.toxicon.2019.04.003. Epub 2019 Apr 14. PMID: 30995453

    Article  CAS  PubMed  Google Scholar 

  72. Durán-Hernández S, Soto-Rodríguez JF, Allen-Bobadilla J, Durán-Hernández N, García-Mosco P. Osteoarthritis of the hip conservative treatment with type A botulinum toxin. Gac Med Mex. 2019;155(Suppl 1):S44–8. https://doi.org/10.24875/GMM.M19000289. PMID: 31638614

    Article  PubMed  Google Scholar 

  73. Boon AJ, Smith J, Dahm DL, Sorenson EJ, Larson DR, Fitz-Gibbon PD, Dykstra DD, Singh JA. Efficacy of intra-articular botulinum toxin type A in painful knee osteoarthritis: a pilot study. PM R. 2010;2(4):268–76. https://doi.org/10.1016/j.pmrj.2010.02.011. PMID: 20430328

    Article  PubMed  Google Scholar 

  74. Sun SF, Hsu CW, Lin HS, Chou YJ, Chen JY, Wang JL. Efficacy of intraarticular botulinum toxin A and intraarticular hyaluronate plus rehabilitation exercise in patients with unilateral ankle osteoarthritis: a randomized controlled trial. J Foot Ankle Res. 2014;7(1):9. https://doi.org/10.1186/1757-1146-7-9. PMID: 24502534; PMCID: PMC3922455

    Article  PubMed  PubMed Central  Google Scholar 

  75. Mendes JG, Natour J, Nunes-Tamashiro JC, Toffolo SR, Rosenfeld A, Furtado RNV. Comparison between intra-articular Botulinum toxin type A, corticosteroid, and saline in knee osteoarthritis: a randomized controlled trial. Clin Rehabil. 2019;33(6):1015–26. https://doi.org/10.1177/0269215519827996. Epub 2019 Feb 19. PMID: 30782000

    Article  PubMed  Google Scholar 

  76. Bao X, Tan JW, Flyzik M, Ma XC, Liu H, Liu HY. Effect of therapeutic exercise on knee osteoarthritis after intra-articular injection of botulinum toxin type A, hyaluronate or saline: a randomized controlled trial. J Rehabil Med. 2018;50(6):534–41. https://doi.org/10.2340/16501977-2340. PMID: 29664106

    Article  PubMed  Google Scholar 

  77. Rezasoltani Z, Dadarkhah A, Tabatabaee SM, Abdorrazaghi F, Kazempour Mofrad M, Kazempour MR. Therapeutic effects of intra-articular botulinum neurotoxin versus physical therapy in knee osteoarthritis. Anesth Pain Med. 2021;11(3):e112789. https://doi.org/10.5812/aapm.112789. PMID: 34540630; PMCID: PMC8438713.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Shukla D, Sreedhar SK, Rastogi V. A comparative study of botulinum toxin: a with triamcinolone compared to triamcinolone alone in the treatment of osteoarthritis of knee. Anesth Essays Res. 2018;12(1):47–9. https://doi.org/10.4103/aer.AER_210_17. PMID: 29628553; PMCID: PMC5872892

    Article  PubMed  PubMed Central  Google Scholar 

  79. Skou ST, Roos EM, Laursen MB, Rathleff MS, Arendt-Nielsen L, Simonsen O, Rasmussen S. A randomized, controlled trial of total knee replacement. N Engl J Med. 2015;373(17):1597–606. https://doi.org/10.1056/NEJMoa1505467. PMID: 26488691

    Article  CAS  PubMed  Google Scholar 

  80. Inacio MCS, Paxton EW, Graves SE, Namba RS, Nemes S. Projected increase in total knee arthroplasty in the United States - an alternative projection model. Osteoarthr Cartil. 2017;25(11):1797–803. https://doi.org/10.1016/j.joca.2017.07.022. Epub 2017 Aug 8. PMID: 28801208

    Article  CAS  Google Scholar 

  81. Lange JK, Lee YY, Spiro SK, Haas SB. Satisfaction rates and quality of life changes following total knee arthroplasty in age-differentiated cohorts. J Arthroplast. 2018;33(5):1373–8. https://doi.org/10.1016/j.arth.2017.12.031. Epub 2017 Dec 29. PMID: 29395722

    Article  Google Scholar 

  82. Anderson JG, Wixson RL, Tsai D, Stulberg SD, Chang RW. Functional outcome and patient satisfaction in total knee patients over the age of 75. J Arthroplast. 1996;11(7):831–40. https://doi.org/10.1016/s0883-5403(96)80183-5. PMID: 8934323

    Article  CAS  Google Scholar 

  83. Baker PN, van der Meulen JH, Lewsey J. Gregg PJ; National Joint Registry for England and Wales. The role of pain and function in determining patient satisfaction after total knee replacement. Data from the National Joint Registry for England and Wales. J Bone Joint Surg Br. 2007;89(7):893–900. https://doi.org/10.1302/0301-620X.89B7.19091. PMID: 17673581

    Article  CAS  PubMed  Google Scholar 

  84. Wylde V, Hewlett S, Learmonth ID, Dieppe P. Persistent pain after joint replacement: prevalence, sensory qualities, and postoperative determinants. Pain. 2011;152(3):566–72. https://doi.org/10.1016/j.pain.2010.11.023. Epub 2011 Jan 15. PMID: 21239114

    Article  PubMed  Google Scholar 

  85. Pritchett JW. Substance P level in synovial fluid may predict pain relief after knee replacement. J Bone Joint Surg Br. 1997;79(1):114–6. https://doi.org/10.1302/0301-620x.79b1.6807. PMID: 9020458

    Article  CAS  PubMed  Google Scholar 

  86. Singh JA, Mahowald ML, Noorbaloochi S. Intraarticular botulinum toxin A for refractory painful total knee arthroplasty: a randomized controlled trial. J Rheumatol. 2010;37(11):2377–86. https://doi.org/10.3899/jrheum.100336. Epub 2010 Sep 1. Erratum in: J Rheumatol. 2011 Jul;38(7):1534. PMID: 20810509; PMCID: PMC3018709.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Singh JA. Efficacy of long-term effect and repeat intraarticular botulinum toxin in patients with painful Total joint arthroplasty: a retrospective study. Br J Med Med Res. 2014;4(1):139–48. https://doi.org/10.9734/BJMMR/2014/4897. PMID: 24319672; PMCID: PMC3850174

    Article  PubMed Central  Google Scholar 

  88. Bong MR, Di Cesare PE. Stiffness after total knee arthroplasty. J Am Acad Orthop Surg. 2004;12(3):164–71. https://doi.org/10.5435/00124635-200405000-00004. PMID: 15161169

    Article  PubMed  Google Scholar 

  89. Smith EB, Shafi KA, Greis AC, Maltenfort MG, Chen AF. Decreased flexion contracture after total knee arthroplasty using Botulinum toxin A: a randomized controlled trial. Knee Surg Sports Traumatol Arthrosc. 2016;24(10):3229–34. https://doi.org/10.1007/s00167-016-4277-9. Epub 2016 Aug 11. PMID: 27515301

    Article  PubMed  Google Scholar 

  90. Boling M, Padua D, Marshall S, Guskiewicz K, Pyne S, Beutler A. Gender differences in the incidence and prevalence of patellofemoral pain syndrome. Scand J Med Sci Sports. 2010;20(5):725–30. https://doi.org/10.1111/j.1600-0838.2009.00996.x. PMID: 19765240; PMCID: PMC2895959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Petersen W, Ellermann A, Gösele-Koppenburg A, Best R, Rembitzki IV, Brüggemann GP, Liebau C. Patellofemoral pain syndrome. Knee Surg Sports Traumatol Arthrosc. 2014;22(10):2264–74. https://doi.org/10.1007/s00167-013-2759-6. Epub 2013 Nov 13. PMID: 24221245; PMCID: PMC4169618

    Article  PubMed  Google Scholar 

  92. Powers CM. Patellar kinematics, part I: the influence of vastus muscle activity in subjects with and without patellofemoral pain. Phys Ther. 2000;80(10):956–64. PMID: 11002431

    Article  CAS  Google Scholar 

  93. Rathleff MS, Rasmussen S, Olesen JL. Utilfredsstillende langtidsresultater efter konservativ behandling af patellofemoralt smertesyndrom [Unsatisfactory long-term prognosis of conservative treatment of patellofemoral pain syndrome]. Ugeskr Laeger. 2012;174(15):1008–13. Danish. PMID: 22487407

    PubMed  Google Scholar 

  94. Stathopulu E, Baildam E. Anterior knee pain: a long-term follow-up. Rheumatology (Oxford). 2003;42(2):380–2. https://doi.org/10.1093/rheumatology/keg093. PMID: 12595641

    Article  CAS  Google Scholar 

  95. Singer BJ, Silbert PL, Dunne JW, Song S, Singer KP. An open label pilot investigation of the efficacy of Botulinum toxin type A [Dysport] injection in the rehabilitation of chronic anterior knee pain. Disabil Rehabil. 2006;28(11):707–13. https://doi.org/10.1080/09638280500301477. PMID: 16809213

    Article  CAS  PubMed  Google Scholar 

  96. Singer BJ, Silbert PL, Song S, Dunne JW, Singer KP. Treatment of refractory anterior knee pain using botulinum toxin type A (Dysport) injection to the distal vastus lateralis muscle: a randomised placebo- controlled crossover trial. Br J Sports Med. 2011;45(8):640–5. https://doi.org/10.1136/bjsm.2009.069781. Epub 2010 Apr 23. PMID: 20418523; PMCID: PMC3106976.

    Article  PubMed  Google Scholar 

  97. Chen JT, Tang AC, Lin SC, Tang SF. Anterior knee pain caused by patellofemoral pain syndrome can be relieved by Botulinum toxin type A injection. Clin Neurol Neurosurg. 2015;129(Suppl 1):S27–9. https://doi.org/10.1016/S0303-8467(15)30008-1. PMID: 25683309

    Article  PubMed  Google Scholar 

  98. Silbert BI, Singer BJ, Silbert PL, Gibbons JT, Singer KP. Enduring efficacy of Botulinum toxin type A injection for refractory anterior knee pain. Disabil Rehabil. 2012;34(1):62–8. https://doi.org/10.3109/09638288.2011.587084. Epub 2011 Sep 22. PMID: 21936736

    Article  PubMed  Google Scholar 

  99. Kesary Y, Singh V, Frenkel-Rutenberg T, Greenberg A, Dekel S, Schwarzkopf R, Snir N. Botulinum toxin injections as salvage therapy is beneficial for management of patellofemoral pain syndrome. Knee Surg Relat Res. 2021;33(1):39. https://doi.org/10.1186/s43019-021-00121-3. PMID: 34715941

    Article  PubMed  PubMed Central  Google Scholar 

  100. Balanta-Melo J, Toro-Ibacache V, Kupczik K, Buvinic S. Mandibular bone loss after masticatory muscles intervention with botulinum toxin: an approach from basic research to clinical findings. Toxins (Basel). 2019;11(2):84. https://doi.org/10.3390/toxins11020084. PMID: 30717172; PMCID: PMC6409568

    Article  CAS  Google Scholar 

  101. Lee HJ, Kim SJ, Lee KJ, Yu HS, Baik HS. Repeated injections of botulinum toxin into the masseter muscle induce bony changes in human adults: a longitudinal study. Korean J Orthod. 2017;47(4):222–8. https://doi.org/10.4041/kjod.2017.47.4.222. Epub 2017 May 26. PMID: 28670563; PMCID: PMC5466904

    Article  PubMed  PubMed Central  Google Scholar 

  102. Raphael KG, Tadinada A, Bradshaw JM, Janal MN, Sirois DA, Chan KC, Lurie AG. Osteopenic consequences of botulinum toxin injections in the masticatory muscles: a pilot study. J Oral Rehabil. 2014;41(8):555–63. https://doi.org/10.1111/joor.12180. Epub 2014 May 17. PMID: 24836732

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Professor Emeritus of Neurology, Yale University School of Medicine, New Haven, CT, USA

    Bahman Jabbari MD, FANN

  2. Clinical Professor of Neurology, University of California, Irvine, CA, USA

    Bahman Jabbari MD, FANN

Authors
  1. Bahman Jabbari MD, FANN
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Jabbari, B. (2022). Botulinum Toxins (BoNTs) for Treatment of Pain in Orthopedic Disorders. In: Botulinum Toxin Treatment of Pain Disorders. Springer, Cham. https://doi.org/10.1007/978-3-030-99650-5_15

Download citation

Publish with us

Policies and ethics

Search

Navigation