Skip to main content

Advertisement

SpringerLink
Log in

Elevated IL-1β and IL-6 levels in lumbar herniated discs in patients with sciatic pain

  • Original Article
  • Published:
European Spine Journal Aims and scope Submit manuscript

Abstract

Purpose

Previous experimental models have shown that proinflammatory cytokines modulate peripheral and central nociception. However, the direct correlation between inflammation and pain in patients remains unclear. Our aim is to correlate the levels of inflammation in the spine with pre- and postoperative pain scores after discectomy.

Methods

Paravertebral muscle, annulus fibrosus (AF) and nucleus pulposus (NP) biopsies were intraoperatively collected from ten lumbar disc hernia (LDH) patients suffering from chronic sciatic pain and, as painless controls, five scoliosis patients. IL-1β and IL-6 expressions in these biopsies were assessed by qPCR and western blot. The amount of pain, indicated on a 0–10 point visual analogue scale (VAS), was assessed 1 day before surgery and 6 weeks and 1 year after surgery. For analysis purposes, LDH patients were grouped into painful (VAS ≥ 3.5) and non-painful (VAS < 3.5). LDH painful patient group showed a onefold increased mRNA expression of IL-1β in the NP, and IL-6 in the AF and NP (p < 0.05 vs. controls).

Results

By western blot analysis, both cytokines were clearly visible in all LDH biopsies, but not in controls. However, cytokine expression of the painful patient group did not differ from those of the non-painful patient group. In addition, there was no correlation between VAS scores and either marker.

Conclusions

These findings support the idea that LDH is accompanied by a local inflammatory process. Yet, the lack of correlation between IL-1β or IL-6 expression and the severity pain suggests that these cytokines may not play a leading role in maintaining a pain generating network.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Valat JP, Genevay S, Marty M et al (2010) Sciatica. Best Pract Res Clin Rheumatol 24:241–252

    Article  PubMed  Google Scholar 

  2. Koes BW, van Tulder MW, Peul WC (2007) Diagnosis and treatment of sciatica. BMJ 334:1313–1317

    Article  PubMed  CAS  Google Scholar 

  3. Vroomen PC, de Krom MC, Slofstra PD et al (2000) Conservative treatment of sciatica: a systematic review. J Spinal Disord 13:463–469

    Article  PubMed  CAS  Google Scholar 

  4. Legrand E, Bouvard B, Audran M et al (2007) Sciatica from disk herniation: medical treatment or surgery? Joint Bone Spine 74:530–535

    Article  PubMed  Google Scholar 

  5. Üçeyler N, Tscharke A, Sommer C (2008) Early cytokine gene expression in mouse CNS after peripheral nerve lesion. Neurosci Lett 436:259–264

    Article  PubMed  Google Scholar 

  6. Ozaktay AC, Kallakuri S, Takebayashi T et al (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

    Article  PubMed  Google Scholar 

  7. Zhou Z, Peng X, Hagshenas J et al (2010) A novel cell–cell signaling by microglial transmembrane TNFα with implications for neuropathic pain. Pain 151:296–306

    Article  PubMed  CAS  Google Scholar 

  8. DeLeo JA, Colburn RW, Rickman AJ (1997) Cytokine and growth factor immunohistochemical spinal profiles in two animal models of mononeuropathy. Brain Res 759:50–57

    Article  PubMed  CAS  Google Scholar 

  9. Schäfers M, Brinkhoff J, Neukirchen S et al (2001) Combined epineurial therapy with neutralizing antibodies to tumor necrosis factor-alpha and interleukin-1 receptor has an additive effect in reducing neuropathic pain in mice. Neurosci Lett 310:113–116

    Article  PubMed  Google Scholar 

  10. Andrade P, Visser-Vandewalle V, Hoffmann C et al (2011) Role of TNF-alpha during central sensitization in preclinical studies. Neurol Sci 32:757–771

    Article  PubMed  Google Scholar 

  11. Üçeyler N, Rogausch JP, Toyka KV et al (2007) Differential expression of cytokines in painful and painless neuropathies. Neurology 69:42–49

    Article  PubMed  Google Scholar 

  12. Koch A, Zacharowski K, Boehm O et al (2007) Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients. Inflamm Res 56:32–37

    Article  PubMed  CAS  Google Scholar 

  13. Üçeyler N, Kafke W, Riediger N et al (2010) Elevated proinflammatory cytokine expression in affected skin in small fiber neuropathy. Neurology 74:1806–1813

    Article  PubMed  Google Scholar 

  14. Wang H, Ahrens C, Rief W et al (2010) Influence of depression symptoms on serum tumor necrosis factor-α of patients with chronic low back pain. Arthritis Res Ther 12:R186

    Article  PubMed  Google Scholar 

  15. Ludwig J, Binder A, Steinmann J et al (2008) Cytokine expression in serum and cerebrospinal fluid in non-inflammatory polyneuropathies. J Neurol Neurosurg Psychiatry 79:1268–1273

    Article  PubMed  CAS  Google Scholar 

  16. Empl M, Renaud S, Erne B et al (2001) TNF-alpha expression in painful and nonpainful neuropathies. Neurology 56:1371–1377

    Article  PubMed  CAS  Google Scholar 

  17. Igarashi A, Kikuchi S, Konno S (2007) Correlation between inflammatory cytokines released from the lumbar facet joint tissue and symptoms in degenerative lumbar spinal disorders. J Orthop Sci 12:154–160

    Article  PubMed  CAS  Google Scholar 

  18. Genevay S, Finckh A, Payer M et al (2008) Elevated levels of tumor necrosis factor-alpha in periradicular fat tissue in patients with radiculopathy from herniated disc. Spine 33:2041–2046

    Article  PubMed  CAS  Google Scholar 

  19. Wang H, Schiltenwolf M, Buchner M (2008) The role of TNF-alpha in patients with chronic low back pain-a prospective comparative longitudinal study. Clin J Pain 24:273–278

    Article  PubMed  Google Scholar 

  20. Ohtori S, Suzuki M, Koshi T et al (2011) Proinflammatory cytokines in the cerebrospinal fluid of patients with lumbar radiculopathy. Eur Spine J 20:942–946

    Article  PubMed  Google Scholar 

  21. Andrade P, Visser-Vandewalle V, Philippens M et al (2011) TNF-alpha levels correlate with postoperative pain severity in lumbar disc hernia patients: opposite clinical effects between TNF receptor 1 and 2. Pain 152:2645–2652

    Article  PubMed  CAS  Google Scholar 

  22. Krämer HH, Eberle T, Uçeyler N et al (2010) TNF-alpha in CRPS and ‘normal’ trauma—significant differences between tissue and serum. Pain 152:285–290

    Article  PubMed  Google Scholar 

  23. Studer R, Vo N, Sowa G et al (2011) Human Nucleus Pulposus Cells React to IL-6: independent actions and amplification of response to IL-1 and TNF-α. Spine 36:593–599

    Article  PubMed  Google Scholar 

  24. Watkins LR, Maier SF, Goehler LE (1995) Immune activation: the role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states. Pain 63:289–302

    Article  PubMed  CAS  Google Scholar 

  25. Xing Z, Gauldie J, Cox G et al (1998) IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 101:311–320

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the Netherlands Organization for Scientific Research (NWO-VENI-916.76.042). We would like to acknowledge Prof. J.J. van Overbeeke and Prof. L.W. van Rhijn for their help to include patients in this study.

Conflict of interest

None of the authors has any potential conflict of interest.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Maastricht University Medical Center, Maastricht, The Netherlands

    Pablo Andrade, Govert Hoogland & Veerle Visser-Vandewalle

  2. Department of Neuroscience, Maastricht University, Universiteitssingel 50, Box 38, 6200 MD, Maastricht, The Netherlands

    Pablo Andrade, Govert Hoogland & Harry W. Steinbusch

  3. European Graduate School of Neuroscience (EURON), Maastricht, The Netherlands

    Pablo Andrade, Govert Hoogland, Harry W. Steinbusch & Veerle Visser-Vandewalle

  4. Maastricht Institute for Neuromodulative Development (MIND), Maastricht, The Netherlands

    Pablo Andrade, Govert Hoogland & Veerle Visser-Vandewalle

  5. Department of Biology, Hunter College, New York, USA

    Miguel A. Garcia

  6. Department of Neurosurgery, Kliniek Klein Rosendael, Rozendaal, The Netherlands

    Marc A. Daemen

Authors
  1. Pablo Andrade
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Govert Hoogland
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miguel A. Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Harry W. Steinbusch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marc A. Daemen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Veerle Visser-Vandewalle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pablo Andrade.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Andrade, P., Hoogland, G., Garcia, M.A. et al. Elevated IL-1β and IL-6 levels in lumbar herniated discs in patients with sciatic pain. Eur Spine J 22, 714–720 (2013). https://doi.org/10.1007/s00586-012-2502-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00586-012-2502-x

Keywords

Search

Navigation