Abstract
Introduction
Interleukin-6 (IL-6) is thought to play a crucial role in the radicular pain caused by lumbar spinal stenosis. However, efficacy of inhibition of IL-6 for sciatica in patients with lumbar spinal stenosis has not been clarified. The purpose of the current study was to examine the effect of the anti-IL-6 receptor monoclonal antibody, tocilizumab, on radicular pain by its epidural administration onto spinal nerves in patients with lumbar spinal stenosis.
Methods
Sixty patients with low back and radicular leg pain caused by spinal stenosis were investigated. In 30 patients, we infiltrated 2.0 mL of lidocaine and 80 mg of tocilizumab onto the affected spinal nerve, and 2.0 mL of lidocaine and 3.3 mg of dexamethasone were used in 30 patients. Low back pain, leg pain, and leg numbness were evaluated during 1 month after spinal nerve infiltration.
Results
Infiltration of tocilizumab was more effective than dexamethasone for leg pain (3 days, 1, 2, and 4 weeks), low back pain (3 days, 1, 2 and 4 weeks), and leg numbness (3 days, 1 and 2 weeks). No adverse event was observed in either group.
Conclusion
Our results indicate that the epidural administration of an anti-IL-6 receptor monoclonal antibody, tocilizumab, onto the spinal nerve produced reduction of radicular leg pain, numbness, and low back pain without adverse event. IL-6 may be one of the inducers of pain caused by spinal stenosis in humans.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Buenaventura RM, Datta S, Abdi S, Smith HS (2009) Systematic review of therapeutic lumbar transforaminal epidural steroid injections. Pain Physician 12:233–251 (review)
Cohen SP, Bogduk N, Dragovich A, Buckenmaier CC 3rd, Griffith S, Kurihara C, Raymond J, Richter PJ, Williams N, Yaksh TL (2009) Randomized, double-blind, placebo-controlled, dose-response, and preclinical safety study of transforaminal epidural etanercept for the treatment of sciatica. Anesthesiology 110:1116–1126
Hurri H, Karppinen J (2004) Discogenic pain. Pain 112:225–228
Igarashi A, Kikuchi S, Konno S, Olmarker K (2004) Inflammatory cytokines released from the facet joint tissue in degenerative lumbar spinal disorders. Spine 29:2091–2095
Ito T, Ohtori S, Inoue G, Koshi T, Doya H, Ozawa T, Saito T, Moriya H, Takahashi K (2007) Glial phosphorylated p38 MAP kinase mediates pain in a rat model of lumbar disc herniation and induces motor dysfunction in a rat model of lumbar spinal canal stenosis. Spine 32:159–167
Kishimoto T (2006) Interleukin-6: discovery of a pleiotropic cytokine. Arthritis Res Ther 8(Suppl 2):S2
Konno S, Yabuki S, Sato K, Olmarker K, Kikuchi S (1995) A model for acute, chronic, and delayed graded compression of the dog cauda equina: presentation of the gross, microscopic, and vascular anatomy of the dog cauda equina and accuracy in pressure transmission of the compression model. Spine 20:2758–2764
Korhonen T, Karppinen J, Malmivaara A, Autio R, Niinimäki J, Paimela L, Kyllönen E, Lindgren KA, Tervonen O, Seitsalo S, Hurri H (2004) Efficacy of infliximab for disc herniation-induced sciatica: one-year follow-up. Spine 29:2115–2119
Korhonen T, Karppinen J, Paimela L, Malmivaara A, Lindgren KA, Järvinen S, Niinimäki J, Veeger N, Seitsalo S, Hurri H (2005) The treatment of disc herniation-induced sciatica with infliximab: results of a randomized, controlled, 3-month follow-up study. Spine 30:2724–2728
Korhonen T, Karppinen J, Paimela L, Malmivaara A, Lindgren KA, Bowman C, Hammond A, Kirkham B, Järvinen S, Niinimäki J, Veeger N, Haapea M, Torkki M, Tervonen O, Seitsalo S, Hurri H (2006) The treatment of disc-herniation-induced sciatica with infliximab: one-year follow-up results of FIRST II, a randomized controlled trial. Spine 31:2759–2766
Mihara M, Kasutani K, Okazaki M, Nakamura A, Kawai S, Sugimoto M, Matsumoto Y, Ohsugi Y (2005) Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family. Int Immunopharmacol 5:1731–1740
Myers RR, Wagner R, Sorkin LS (1999) Hyperalgesic actions of cytokines on peripheral nerves. In: Watkins LR, Maier SF (eds) Cytokines and pain. Birkhauser, Basel, pp 133–157
Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J, Kishimoto T (2009) Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy. Mod Rheumatol 19:12–19
Noponen-Hietala N, Virtanen I, Karttunen R, Schwenke S, Jakkula E, Li H, Merikivi R, Barral S, Ott J, Karppinen J, Ala-Kokko L (2005) Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica. Pain 114:186–194
Ohtori S, Suzuki M, Koshi T, Takaso M, Yamashita M, Inoue G, Yamauchi K, Orita S, Eguchi Y, Kuniyoshi K, Ochiai N, Kishida S, Nakamura J, Aoki Y, Ishikawa T, Arai G, Miyagi M, Kamoda H, Suzuki M, Toyone T, Takahashi K (2011) Proinflammatory cytokines in the cerebrospinal fluid of patients with lumbar radiculopathy. Eur Spine J 20:942–946
Ohtori S, Miyagi M, Eguchi Y, Inoue G, Orita S, Ochiai N, Kishida S, Kuniyoshi K, Nakamura J, Aoki Y, Ishikawa T, Arai G, Kamoda H, Suzuki M, Takaso M, Furuya T, Toyone T, Takahashi K (2011) Epidural administration of spinal nerves with the tumor necrosis factor-alpha inhibitor, etanercept, compared with dexamethasone for treatment of sciatica in patients with lumbar spinal stenosis: a prospective randomized study. Spine (Epub ahead of print)
Olmarker K, Rydevik B, Nordborg C (1993) Autologous nucleus pulposus induces neurophysiologic and histologic changes in porcine cauda equina nerve roots. Spine 18:1425–1432
Olmarker K, Larsson K (1998) Tumor necrosis factor alpha and nucleus-pulposus-induced nerve root injury. Spine 23:2538–2544
Olmarker K, Nutu M, Størkson R (2003) Changes in spontaneous behavior in rats exposed to experimental disc herniation are blocked by selective TNF-alpha inhibition. Spine 28:1635–1642
Onda A, Murata Y, Rydevik B, Larsson K, Kikuchi S, Olmarker K (2004) Infliximab attenuates immunoreactivity of brain-derived neurotrophic factor in a rat model of herniated nucleus pulposus. Spine 29:1857–1861
Ozaktay AC, Kallakuri S, Takebayashi T, Cavanaugh JM, Asik I, DeLeo JA, Weinstein JN (2006) Effects of interleukin-1 beta, interleukin-6, and tumor necrosis factor on sensitivity of dorsal root ganglion and peripheral receptive fields in rats. Eur Spine J 15:1529–1537
Pocock SJ, Simon R (1975) Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics 31:103–115
Riew KD, Yin Y, Gilula L, Bridwell KH, Lenke LG, Lauryssen C, Goette K (2000) The effect of nerve root injections on the need for operative treatment of lumbar radicular pain. J Bone Jt Surg Am 82A:1589–1593
Sekiguchi M, Kikuchi S, Myers RR (2004) Experimental spinal stenosis: relationship between degree of cauda equina compression, neuropathology, and pain. Spine 29:1105–1111
Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, OPTION Investigators (2008) Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebocontrolled, randomised trial. Lancet 371:987–997
Conflict of interest
The authors did not receive and will not receive any benefits or funding from any commercial party related directly or indirectly to the subject of this article.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ohtori, S., Miyagi, M., Eguchi, Y. et al. Efficacy of epidural administration of anti-interleukin-6 receptor antibody onto spinal nerve for treatment of sciatica. Eur Spine J 21, 2079–2084 (2012). https://doi.org/10.1007/s00586-012-2183-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00586-012-2183-5