Skip to main content
SpringerLink
Log in

A novel model of inflammatory pain in human skin involving topical application of sodium lauryl sulfate

Inflammation Research Aims and scope Submit manuscript

Cite this article

Abstract

Objective and design

Sodium lauryl sulfate (SLS) is a known irritant. It releases pro-inflammatory mediators considered pivotal in inflammatory pain. The sensory effects of SLS in the skin remain largely unexplored. In this study, SLS was evaluated for its effect on skin sensory functions.

Subjects

Eight healthy subjects were recruited for this study.

Treatment

Skin sites were randomized to topical SLS 0.25, 0.5, 1, 2% and vehicle for 24 h. Topical capsaicin 1% was applied for 30 min at 24 h after SLS application.

Methods

Assessments included laser Doppler imaging of local vasodilation and flare reactions, rating of spontaneous pain, assessment of primary thermal and tactile hyperalgesia, and determination of secondary dynamic and static hyperalgesia.

Results

SLS induced significant and dose-dependent local inflammation and primary hyperalgesia to tactile and thermal stimulation at 24 h after application, with SLS 2% treatment eliciting results comparable to those observed following treatment with capsaicin 1%. SLS induced no spontaneous pain, small areas of flare, and minimal secondary hyperalgesia. The primary hyperalgesia vanished within 2–3 days, whereas the skin inflammation persisted and was only partly normalized by Day 6.

Conclusions

SLS induces profound perturbations of skin sensory functions lasting 2–3 days. SLS-induced inflammation may be a useful model for studying the mechanisms of inflammatory pain.

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

References

  1. Tupker RA, Willis C, Berardesca E, Lee CH, Fartasch M, Agner T, et al. Guidelines on sodium lauryl sulfate (SLS) exposure tests A report from the Standardization Group of the European Society of Contact Dermatitis. Contact Derm. 1997;37:53–69.

    Article  CAS  PubMed  Google Scholar 

  2. Verri WA Jr, Cunha TM, Parada CA, Poole S, Cunha FQ, Ferreira SH. Hypernociceptive role of cytokines and chemokines: targets for analgesic drug development? Pharmacol Ther. 2006;112:116–38.

    Article  CAS  PubMed  Google Scholar 

  3. Thacker MA, Clark AK, Marchand F, McMahon SB. Pathophysiology of peripheral neuropathic pain: immune cells and molecules. Anesth Analg. 2007;105:838–47.

    Article  PubMed  Google Scholar 

  4. Spiekstra SW, Toebak MJ, Sampat-Sardjoepersad S, van Beek PJ, Boorsma DM, Stoof TJ, et al. Induction of cytokine (interleukin-1alpha and tumor necrosis factor-alpha) and chemokine (CCL20, CCL27, and CXCL8) alarm signals after allergen and irritant exposure. Exp Dermatol. 2005;14:109–16.

    Article  CAS  PubMed  Google Scholar 

  5. Piguet PF, Grau GE, Hauser C, Vassalli P. Tumor necrosis factor is a critical mediator in hapten induced irritant and contact hypersensitivity reactions. J Exp Med. 1991;173:673–9.

    Article  CAS  PubMed  Google Scholar 

  6. Effendy I, Loffler H, Maibach HI. Epidermal cytokines in murine cutaneous irritant responses. J Appl Toxicol. 2000;20:335–41.

    Article  CAS  PubMed  Google Scholar 

  7. Niwa M, Nagai K, Oike H, Kobori M. Evaluation of the skin irritation using a DNA microarray on a reconstructed human epidermal model. Biol Pharm Bull. 2009;32:203–8.

    Article  CAS  PubMed  Google Scholar 

  8. Hunziker T, Brand CU, Kapp A, Waelti ER, Braathen LR. Increased levels of inflammatory cytokines in human skin lymph derived from sodium lauryl sulphate-induced contact dermatitis. Br J Dermatol. 1992;127:254–7.

    Article  CAS  PubMed  Google Scholar 

  9. de Jongh CM, Lutter R, Verberk MM, Kezic S. Differential cytokine expression in skin after single and repeated irritation by sodium lauryl sulphate. Exp Dermatol. 2007;16:1032–40.

    Article  PubMed  Google Scholar 

  10. Ulfgren AK, Klareskog L, Lindberg M. An immunohistochemical analysis of cytokine expression in allergic and irritant contact dermatitis. Acta Derm Venereol. 2000;80:167–70.

    Article  CAS  PubMed  Google Scholar 

  11. Eberhard Y, Ortiz S, Ruiz LA, Kuznitzky R, Serra HM. Up-regulation of the chemokine CCL21 in the skin of subjects exposed to irritants. BMC Immunol. 2004;5:7–15.

    Article  PubMed  Google Scholar 

  12. Loffler H, Aramaki J, Effendy I. Response to thermal stimuli in skin pretreated with sodium lauryl sulfate. Acta Derm Venereol. 2001;81:395–7.

    Article  CAS  PubMed  Google Scholar 

  13. Pedersen JL, Kehlet H. Hyperalgesia in a human model of acute inflammatory pain: a methodological study. Pain. 1998;74:139–51.

    Article  CAS  PubMed  Google Scholar 

  14. Rolke R, Magerl W, Campbell KA, Schalber C, Caspari S, Birklein F, et al. Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur J Pain. 2006;10:77–88.

    Article  CAS  PubMed  Google Scholar 

  15. Sandkuhler J. Models and mechanisms of hyperalgesia and allodynia. Physiol Rev. 2009;89:707–58.

    Article  PubMed  Google Scholar 

  16. Hoffmann RT, Schmelz M. Time course of UVA- and UVB-induced inflammation and hyperalgesia in human skin. Eur J Pain. 1999;3:131–9.

    Article  PubMed  Google Scholar 

  17. Sycha T, Gustorff B, Lehr S, Tanew A, Eichler HG, Schmetterer L. A simple pain model for the evaluation of analgesic effects of NSAIDs in healthy subjects. Br J Clin Pharmacol. 2003;56:165–72.

    Article  CAS  PubMed  Google Scholar 

  18. Kilo S, Forster C, Geisslinger G, Brune K, Handwerker HO. Inflammatory models of cutaneous hyperalgesia are sensitive to effects of ibuprofen in man. Pain. 1995;62:187–93.

    Article  CAS  PubMed  Google Scholar 

  19. Chassaing C, Schmidt J, Eschalier A, Cardot JM, Dubray C. Hyperalgesia induced by cutaneous freeze injury for testing analgesics in healthy volunteers. Br J Clin Pharmacol. 2006;61:389–97.

    Article  CAS  PubMed  Google Scholar 

  20. Rukwied R, Mayer A, Kluschina O, Obreja O, Schley M, Schmelz M. NGF induces non-inflammatory localized and lasting mechanical and thermal hypersensitivity in human skin. Pain. 2010;148:407–13.

    Article  CAS  PubMed  Google Scholar 

  21. Fullerton A, Rode B, Serup J. Skin irritation typing and grading based on laser Doppler perfusion imaging. Skin Res Technol. 2002;8:23–31.

    Article  PubMed  Google Scholar 

  22. Gloor M, Senger B, Langenauer M, Fluhr JW. On the course of the irritant reaction after irritation with sodium lauryl sulphate. Skin Res Technol. 2004;10:144–8.

    Article  PubMed  Google Scholar 

  23. Fairweather I, McGlone F, Reilly D, Rukwied R. Controlled dermal cell damage as human in vivo model for localised pain and inflammation. Inflamm Res. 2004;53:118–23.

    Article  CAS  PubMed  Google Scholar 

  24. Koltzenburg M, Torebjork HE, Wahren LK. Nociceptor modulated central sensitization causes mechanical hyperalgesia in acute chemogenic and chronic neuropathic pain. Brain. 1994;117(Pt 3):579–91.

    Article  PubMed  Google Scholar 

  25. Bishop T, Ballard A, Holmes H, Young AR, McMahon SB. Ultraviolet-B induced inflammation of human skin: Characterisation and comparison with traditional models of hyperalgesia. Eur J Pain. 2009;13:524–32.

    Article  CAS  PubMed  Google Scholar 

  26. Wallengren J, Hakanson R. Effects of capsaicin, bradykinin and prostaglandin E2 in the human skin. Br J Dermatol. 1992;126:111–7.

    Article  CAS  PubMed  Google Scholar 

  27. Schwarz T, Luger TA. Effect of UV irradiation on epidermal cell cytokine production. J Photochem Photobiol B. 1989;4:1–13.

    Article  CAS  PubMed  Google Scholar 

  28. Willis CM, Stephens CJ, Wilkinson JD. Differential patterns of epidermal leukocyte infiltration in patch test reactions to structurally unrelated chemical irritants. J Invest Dermatol. 1993;101:364–70.

    Article  CAS  PubMed  Google Scholar 

  29. Scheynius A, Fischer T, Forsum U, Klareskog L. Phenotypic characterization in situ of inflammatory cells in allergic and irritant contact dermatitis in man. Clin Exp Immunol. 1984;55:81–90.

    CAS  PubMed  Google Scholar 

  30. Avnstorp C, Ralfkiaer E, Jorgensen J, Wantzin GL. Sequential immunophenotypic study of lymphoid infiltrate in allergic and irritant reactions. Contact Derm. 1987;16:239–45.

    Article  CAS  PubMed  Google Scholar 

  31. Urbanski A, Schwarz T, Neuner P, Krutmann J, Kirnbauer R, Kock A, et al. Ultraviolet light induces increased circulating interleukin-6 in humans. J Invest Dermatol. 1990;94:808–11.

    Article  CAS  PubMed  Google Scholar 

  32. Scholzen TE, Brzoska T, Kalden DH, O’Reilly F, Armstrong CA, Luger TA, et al. Effect of ultraviolet light on the release of neuropeptides and neuroendocrine hormones in the skin: mediators of photodermatitis and cutaneous inflammation. J Investig Dermatol Symp Proc. 1999;4:55–60.

    Article  CAS  PubMed  Google Scholar 

  33. Yoshizumi M, Nakamura T, Kato M, Ishioka T, Kozawa K, Wakamatsu K, et al. Release of cytokines/chemokines and cell death in UVB-irradiated human keratinocytes, HaCaT. Cell Biol Int. 2008;32:1405–11.

    Article  CAS  PubMed  Google Scholar 

  34. Angst MS, Clark JD, Carvalho B, Tingle M, Schmelz M, Yeomans DC. Cytokine profile in human skin in response to experimental inflammation, noxious stimulation, and administration of a COX-inhibitor: a microdialysis study. Pain. 2008;139:15–27.

    Article  CAS  PubMed  Google Scholar 

  35. Summer GJ, Romero-Sandoval EA, Bogen O, Dina OA, Khasar SG, Levine JD. Proinflammatory cytokines mediating burn-injury pain. Pain. 2008;135:98–107.

    Article  CAS  PubMed  Google Scholar 

  36. Opree A, Kress M. Involvement of the proinflammatory cytokines tumor necrosis factor-alpha, IL-1 beta, and IL-6 but not IL-8 in the development of heat hyperalgesia: effects on heat-evoked calcitonin gene-related peptide release from rat skin. J Neurosci. 2000;20:6289–93.

    CAS  PubMed  Google Scholar 

  37. Gustorff B, Anzenhofer S, Sycha T, Lehr S, Kress HG. The sunburn pain model: the stability of primary and secondary hyperalgesia over 10 hours in a crossover setting. Anesth Analg. 2004;98:173–7. (table).

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The study was supported by research grants from the Rosa and Asta Jensen Foundation and the Viborg Hospital Research Foundation.

Author information

Authors and Affiliations

  1. Laboratory of Experimental Physiology and Inflammation, Department of Clinical Physiology, Viborg Hospital, Heibergs Alle 4, 8800, Viborg, Denmark

    L. J. Petersen & A. M. Lyngholm

  2. Department of Health Sciences and Technology, Center for Sensory-Motor Interaction, Aalborg University, Fredrik Bajersvej 7-D3, 9220, Aalborg, Denmark

    L. Arendt-Nielsen

Authors
  1. L. J. Petersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. M. Lyngholm
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Arendt-Nielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. J. Petersen.

Additional information

Responsible Editor: G. Geisslinger.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Petersen, L.J., Lyngholm, A.M. & Arendt-Nielsen, L. A novel model of inflammatory pain in human skin involving topical application of sodium lauryl sulfate. Inflamm. Res. 59, 775–781 (2010). https://doi.org/10.1007/s00011-010-0189-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-010-0189-1

Keywords

search

Navigation