Botulinum Neurotoxins and Chronic Low Back Pain

  • Bahman Jabbari


Chronic low back pain is a common condition with diverse etiologies. It is a major cause of functional impairment and disability. In recent years, our understanding of the pathophysiology of low back pain has improved significantly especially in regard to the contribution of dorsal root ganglia and pain mediators. The treatment of chronic low back pain is challenging. Most drugs have limited or short-term efficacy, and many produce undesirable side effects. In animal models, botulinum neurotoxins (BoNTs) have shown analgesic effects through different mechanisms. In human, onaA is effective in chronic migraine, and data suggests efficacy in other forms of neuropathic pain. Using the same dose and technique (multilevel injection into erector spinae), one class II (double blind, placebo controlled) and one prospective, 16-month, open-label study have provided evidence of possible efficacy (level C) in chronic low back pain. Future studies should focus on etiologically distinct subgroups of patients with chronic LBP and take advantage of using the dose and techniques that have already shown promising results.


Botulinum toxin Botulinum neurotoxin Low back pain Chronic low back pain OnabotulinumtoxinA AbobotulinumtoxinA 

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  1. Andersson GBJ. Epidemiological features of chronic low-back pain. Lancet. 1999;354:581–5.CrossRefPubMedGoogle Scholar
  2. Calvo-Muñoz I, Gómez-Conesa A, Sánchez-Meca J. Physical therapy treatments for low back pain in children and adolescents: a meta-analysis. BMC Musculoskelet Disord. 2013;14:55.CrossRefPubMedCentralPubMedGoogle Scholar
  3. Carragee E, Cohen S. Reliability of LBP history in asymptomatic subjects? The prevalence and incidence of reported back pain correlates with surveillance frequency. In: Proceedings of the 19th Annual Meeting of the North American Spine Society, Chicago. 2004;216:26–30.Google Scholar
  4. Chaparro LE, Furlan AD, Deshpande A, Mailis-Gagnon A, Atlas S, Turk DC. Opioids compared to placebo or other treatments for chronic low back pain: an update of the Cochrane review. Spine. 2014;39:556–63.Google Scholar
  5. Coats TL, Borenstein DG, Nangia NK, Brown MT. Effects of valdecoxib in the treatment of chronic low back pain: results of a randomized, placebo-controlled trial. Clin Ther. 2004;26:1249–60.CrossRefPubMedGoogle Scholar
  6. Cramer H, Lauche R, Haller H, Dobos G. A systematic review and meta-analysis of yoga for low back pain. Clin J Pain. 2013;29:450–60.CrossRefPubMedGoogle Scholar
  7. Cui M, Khanijou S, Rubino J, Aoki KR. Pain. Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain. 2004;107:125–33.CrossRefPubMedGoogle Scholar
  8. da Silva LB, Kulas D, Karshenas A, Cairns BE, Bach FW, Arendt-Nielsen L, Gazerani P. Time course analysis of the effects of botulinum neurotoxin type a on pain and vasomotor responses evoked by glutamate injection into human temporalis muscles. Toxins (Basel). 2014;6:592–607.CrossRefGoogle Scholar
  9. De Andrés J, Adsuara VM, Palmisani S, Villanueva V, López-Alarcón MD. A double-blind, controlled, randomized trial to evaluate the efficacy of botulinum toxin for the treatment of lumbar myofascial pain in humans. Reg Anesth Pain Med. 2010;35:255–60.CrossRefPubMedGoogle Scholar
  10. Dubinsky RM, Miyasaki J. Assessment: efficacy of transcutaneous electric nerve stimulation in the treatment of pain in neurologic disorders (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. 2010;74: 173–176.Google Scholar
  11. Filippi GM, Errico P, Santarelli R, Bagolini B, Manni E. Botulinum A toxin effects on rat jaw muscle spindles. Acta Otolaryngol. 1993;113:400–4.CrossRefPubMedGoogle Scholar
  12. Foster L, Clapp L, Erickson M, Jabbari B. Botulinum toxin A and chronic low back pain: a randomized, double blind study. Neurology. 2001;56:1290–3.CrossRefPubMedGoogle Scholar
  13. Frymoyer JW, Cats-Baril WL. An overview of the incidences and costs of low back pain. Orthop Clin North Am. 1991;22:263–71.PubMedGoogle Scholar
  14. Gimbel J, Linn R, Hale M, Nicholson B. Lidocaine patch treatment in patients with low back pain: results of an open-label, nonrandomized pilot study. Am J Ther. 2005;12:311–9.CrossRefPubMedGoogle Scholar
  15. Harrington JF, Messier AA, Bereiter D, Barnes B, Epstein MH. Herniated lumbar disc material as a source of free glutamate available to affect pain signals through the dorsal root ganglion. Spine (Phila Pa 1976). 2000;25:929–36.CrossRefGoogle Scholar
  16. Howe JF, Loeser JD, Calvin WH. Mechanosensitivity of dorsal root ganglia and chronically injured axons: a physiological basis for the radicular pain of nerve root compression. Pain. 1977;3:25–41.CrossRefPubMedGoogle Scholar
  17. Iwase T, Takebayashi T, Tanimoto K, Terashima Y, Miyakawa T, Kobayashi T, Tohse N, Yamashita T. Sympathectomy attenuates excitability of dorsal root ganglion neurons and pain behaviour in a lumbar radiculopathy model. Bone Joint Res. 2012;1:198–204.CrossRefPubMedCentralPubMedGoogle Scholar
  18. Jabbari B, Machado GD. Treatment of refractory pain with botulinum toxins-an evidence based review. Pain Med. 2011;12:1594–606.CrossRefPubMedGoogle Scholar
  19. Jabbari B, Ney J, Sichani A, Monacci W, Foster L, Difazio M. Treatment of refractory, chronic low back pain with botulinum neurotoxin A: an open-label, pilot study. Pain Med. 2006;7:260–4.CrossRefPubMedGoogle Scholar
  20. Jung WW, Kim HS, Shon JR, Lee M, Lee SH, Sul D, Na HS, Kim JH, Kim BJ. Intervertebral disc degeneration-induced expression of pain-related molecules: glial cell-derived neurotropic factor as a key factor. J Neurosurg Anesthesiol. 2011;23:329–34.CrossRefPubMedGoogle Scholar
  21. Kobayashi Y, Kurata J, Sekiguchi M, Kokubun M, Akaishizawa T, Chiba Y, Konno S, Kikuchi S. Augmented cerebral activation by lumbar mechanical stimulus in chronic low back pain patients: an FMRI study. Spine (Phila Pa 1976). 2009;34:2431–6.CrossRefGoogle Scholar
  22. Maniakadis N, Gray A. The economic burden of back pain in UK. Pain. 2000;84:95–103.CrossRefGoogle Scholar
  23. 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;155:674–84.CrossRefPubMedGoogle Scholar
  24. McLachlan EM, Hu P. Inflammation in dorsal root ganglia after peripheral nerve injury: effects of the sympathetic innervation. Auton Neurosci. 2014;182:108–17.CrossRefPubMedGoogle Scholar
  25. McLachlan EM, Jänig W, Devor M, Michaelis M. Peripheral nerve injury triggers noradrenergic sprouting within dorsal root ganglia. Nature. 1993;363:543–6.CrossRefPubMedGoogle Scholar
  26. Miyagi M, Ishikawa T, Orita S, Eguchi Y, Kamoda H, Arai G, Suzuki M, Inoue G, Aoki Y, Toyone T, Takahashi K, Ohtori S. Disk injury in rats produces persistent increases in pain-related neuropeptides in dorsal root ganglia and spinal cord glia but only transient increases in inflammatory mediators: pathomechanism of chronic diskogenic low back pain. Spine (Phila Pa 1976). 2011;36:2260–6.CrossRefGoogle Scholar
  27. Nathan ST, Roberts CS, Deliberato D, Nathan ST, Roberts CS, Deliberato D. Lumbar paraspinal compartment syndrome. Int Orthop. 2012;36:1221–7.CrossRefPubMedCentralPubMedGoogle Scholar
  28. Naumann M, So Y, Argoff CE, Childers MK, Dykstra DD, Gronseth GS, Jabbari B, Kaufmann HC, Schurch B, Silberstein SD, Simpson DM. Therapeutics and technology assessment subcommittee of the American Academy of Neurology- Assessment: botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008;70:1707–14.CrossRefPubMedGoogle Scholar
  29. Nilsson E, Brisby H, Rask K, Hammar I. Mechanical compression and nucleus pulposus application on dorsal root Ganglia differentially modify evoked neuronal activity in the thalamus. Bioresour Open Access. 2013;2:192–8.CrossRefGoogle Scholar
  30. Nussmeier NA, Whelton AA, Brown MT, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med. 2005;352:1081–91.CrossRefPubMedGoogle Scholar
  31. Ohtori S, Inoue G, Koshi T, Ito T, Yamashita M, Yamauchi K, Suzuki M, Doya H, Moriya H, Takahashi Y, Takahashi K. Characteristics of sensory dorsal root ganglia neurons innervating the lumbar vertebral body in rats. J Pain. 2007;8:483–8.CrossRefPubMedGoogle Scholar
  32. Ostelo R, Tulder M, Vlaeyen J, Linton S, Morley S, Assendelft W. Behavioral treatment for chronic low-back pain. Cochrane Database Syst Rev. 2005;1, CD002014.PubMedGoogle Scholar
  33. Parr AT, Manchikanti L, Hameed H, Conn A, Manchikanti KN, Benyamin RM, Diwan S, Singh V, Abdi S. Caudal epidural injections in the management of chronic low back pain: a systematic appraisal of the literature. Pain Physician. 2012;15:E159-98.Google Scholar
  34. Rand MJ, Whaler BC. Impairment of sympathetic transmission by botulinum toxin. Nature. 1965;206:588–91.CrossRefPubMedGoogle Scholar
  35. Roberts WJ. A hypothesis on he physiological basis for causalgia and related pains. Pain. 1986;24: 297–311.Google Scholar
  36. Rubinstein SM, van Middelkoop M, Kuijpers T, Ostelo R, Verhagen AP, de Boer MR, Koes BW, van Tulder MW. A systematic review on the effectiveness of complementary and alternative medicine for chronic non-specific low-back pain. Eur Spine J. 2010;19:1213–28.CrossRefPubMedCentralPubMedGoogle Scholar
  37. Rubinstein SM, van Middelkoop M, Assendelft WJ, de Boer MR, van Tulder MW. Spinal manipulative therapy for chronic low-back pain: an update of a Cochrane review. Spine. 2011;36:E825–46.CrossRefPubMedGoogle Scholar
  38. Sadamasu A, Sakuma Y, Suzuki M, Orita S, Yamauchi K, Inoue G, Aoki Y, Ishikawa T, Miyagi M, Kamoda H, Kubota G, Oikawa Y, Inage K, Sainoh T, Sato J, Nakamura J, Toyone T, Takahashi K, Ohtori S. Upregulation of NaV1.7 in dorsal root ganglia after intervertebral disc injury in rats. Spine (Phila Pa 1976). 2014;39:E421–6.CrossRefGoogle Scholar
  39. Schmidt CP, Zwingenberger S, Walther A, Reuter U, Kasten P, Seifert J, Günther KP, Stiehler M. Prevalence of low back pain in adolescent athletes – an epidemiological investigation. Int J Sports Med. 2014;35:684–89.Google Scholar
  40. Seco J, Kovacs FM, Urrutia G. The efficacy, safety, effectiveness, and cost-effectiveness of ultrasound and shock wave therapies for low back pain: a systematic review. Spine J. 2011;11:966–77.CrossRefPubMedGoogle Scholar
  41. Solomon SD, McMurray JJV, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M. Adenoma Prevention with Celecoxib (APC) Study Investigators. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005;352:1071–80.CrossRefPubMedGoogle Scholar
  42. Speed C. Low back pain. Br Med J. 2004;328:1119–21.CrossRefGoogle Scholar
  43. Spoor AB, Öner FC. Minimally invasive spine surgery in chronic low back pain patients. J Neurosurg Sci. 2013;57:203–18.PubMedGoogle Scholar
  44. Staiger TO, Gaster B, Sullivan MD, Deyo RA. Systematic review of antidepressants in the treatment of chronic low back pain. Spine. 2003;28:2540–5.CrossRefPubMedGoogle Scholar
  45. Uhl RL, Roberts TT, Papaliodis DN, Mulligan MT, Dubin AH. Management of chronic musculoskeletal pain. J Am Acad Orthop Surg. 2014;22:101–10.CrossRefPubMedGoogle Scholar
  46. Van Tulder MW, Scholten RJ, Koes BW, Deyo RA. Nonsteroidal anti-inflammatory drugs for low back pain: a systematic review within the framework of the Cochrane Collaboration Back Review Group. Spine. 2000;25:2501–13.CrossRefPubMedGoogle Scholar
  47. Van Tulder MW, Ostelo R, Vlaeyen JW, Linton SJ, Morley SJ, Assendelft WJ. Behavioral treatment for chronic low back pain: a systematic review within the framework of the Cochrane Back Review Group. Spine. 2001;26:270–81.CrossRefPubMedGoogle Scholar
  48. Van Tulder MW, Touray T, Furlan AD, Solway S, Bouter LM, Cochrane Back Review Group. Muscle relaxants for non-specific low back pain: a systematic review within the framework of the Cochrane collaboration. Spine (Phila Pa 1976). 2003;28:1978–92. Review.CrossRefGoogle Scholar
  49. Vorsanger GJ, Xiang J, Gana TJ, Pascual ML, Fleming RR. Extended-release tramadol (tramadol ER) in the treatment of chronic low back pain. J Opioid Manag. 2008;4:87–97.PubMedGoogle Scholar
  50. Wakai K, Ohtori S, Yamashita M, Yamauchi K, Inoue G, Suzuki M, Orita S, Eguchi Y, Ochiai N, Kishida S, Takaso M, Fukui Y, Hayashi Y, Aoki Y, Kuniyoshi K, Nakamura J, Ishikawa T, Arai G, Miyagi M, Kamoda H, Takahashi K. Primary sensory neurons with dichotomizing axons projecting to the facet joint and the low back muscle in rats. J Orthop Sci. 2010;15:402–6.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Bahman Jabbari
    • 1
  1. 1.Botulinum Toxin Treatment ProgramYale School of MedicineNew HavenUSA

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