Pain associated with photodynamic therapy using 5-aminolevulinic acid or 5-aminolevulinic acid methylester on tape-stripped normal skin
Abstract
BACKGROUND: Pain during and after topical photodynamic therapy (PDT) is one of the few severe adverse effects of the new treatment of skin diseases. OBJECTIVE: To compare the pain experienced in normal skin treated with 5-aminolevulinic acid (ALA) PDT and 5-aminolevulinic methylester (ALA-ME) PDT. DESIGN: Double-blind randomized trial. INTERVENTIONS: Twenty healthy volunteers were treated randomly with ALA-PDT on one forearm and ALA-ME-PDT on the other forearm after tape stripping of the sun-exposed skin areas. MAIN OUTCOME MEASURES: Pain was scored using a numerical scale ranging from 0 to 10 during illumination, immediately after illumination, and each day in the following week. In addition, we measured erythema, pigmentation, and protoporphyrin IX (PpIX) fluorescence. RESULTS: ALA-PDT generated significantly more pain than ALA-ME-PDT during and after illumination (P =.001 and P =.05, respectively). ALA-PDT induced a larger decrease in PpIX fluorescence than ALA-ME-PDT (P =.009). There was no correlation between pain and peak PpIX fluorescence or absolute decrease in peak PpIX fluorescence. Both treatments lead to erythema immediately after illumination and increased pigmentation 1 week after PDT. There was no correlation between pain and degree of erythema or pigmentation. CONCLUSIONS: ALA-ME-PDT was less painful than ALA-PDT when performed on tape-stripped normal skin. The pain scores did not correlate with the intensity of peak PpIX fluorescence in the skin or with the degree of erythema after illumination, suggesting that pain was not caused by activation of PpIX alone. The theory that ALA and not ALA-ME is transported by gamma-aminobutyric acid receptors into the peripheral nerve endings may explain the higher pain scores in ALA-PDT-treated areas.
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MAL/PDT is associated with decreased pain levels compared to ALA/PDT.
“As above, MAL/PDT is associated with decreased pain levels compared to ALA/PDT [19,20].”
From Photodynamic Therapy for Non-Melanoma Skin Cancers (2016) · cites this paper as [19]
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Nissen, C., Philipsen, P. A., & Wulf, H. C. (2015) · British Journal of Dermatology · doi:10.1111/bjd.13923 · Cited by 19 · see citing works
Martin, G. M. (2016) · PubMed Central · Cited by 19 · see citing works
Yazdanyar, S., Zarchi, K., & Jemec, G. B. E. (2017) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2017.07.010 · Cited by 19 · see citing works
Kleinpenning, M. M., van de Kerkhof, P. C. M., & Gerritsen, R. M. J. P. (2009) · Journal of Dermatological Treatment · doi:10.3109/09546630903271555 · Cited by 17 · see citing works
Kiesslich, T., Helander, L., Illig, R., Oberdanner, C. B., Wagner, A., Lettner, H., Jakab, M., & Plaetzer, K. (2014) · Journal of Biomedical Optics · doi:10.1117/1.jbo.19.8.085007 · Cited by 16 · see citing works
Manifold, R. N., & Anderson, C. D. (2011) · Archives of Dermatological Research · doi:10.1007/s00403-011-1128-x · Cited by 15 · see citing works
Ibbotson, S. H., Valentine, R. M., & Hearn, R. (2012) · Photodermatology Photoimmunology & Photomedicine · doi:10.1111/j.1600-0781.2012.00684.x · Cited by 15 · see citing works
Different pain sensations in photodynamic therapy of nodular basal cell carcinoma
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Steinbauer, J., Schreml, S., Karrer, S., Ackermann, G., Babilas, P., Landthaler, M., & Szeimies, R. (2009) · Photodermatology Photoimmunology & Photomedicine · doi:10.1111/j.1600-0781.2009.00455.x · Cited by 14 · see citing works
Fabricius, S., Lerche, C. M., Philipsen, P. A., & Wulf, H. C. (2012) · Photochemical & Photobiological Sciences · doi:10.1039/c2pp25128k · Cited by 14 · see citing works
Changes in human skin after topical PDT with hexyl aminolevulinate
Juzeniene, A., Nielsen, K. P., Zhao, L., Ryzhikov, G. A., Biryulina, M. S., Stamnes, J. J., Stamnes, K. H., & Moan, J. E. (2008) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2008.07.001 · Cited by 14 · see citing works
Photodynamic therapy-induced inflammation and adverse effects: An updated review
Moloudi, K., Abrahamse, H., & George, B. P. A. (2025) · Biomedical Journal · doi:10.1016/j.bj.2025.100889 · Cited by 11 · see citing works
The application of photodynamic therapy in plastic and reconstructive surgery
Wu, M. H., Huang, X., Gao, L., Zhou, G., & Xie, F. (2022) · Frontiers in Chemistry · doi:10.3389/fchem.2022.967312 · Cited by 11 · see citing works
Photodynamic Therapy and Skin Cancer
Papakonstantinou, E., Löhr, F., & Raap, U. (2018) · InTech eBooks · doi:10.5772/intechopen.70309 · Cited by 9 · see citing works
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Neittaanmäki, N., Neittaanmäki, E., Pölönen, I., Snellman, E., & Grönroos, M. (2015) · Acta Dermato Venereologica · doi:10.2340/00015555-2131 · Cited by 8 · see citing works
Skin-Directed Therapies in Mycosis Fungoides: An Update
Tota, M., Łyko, M., Misiąg, P., Łacwik, J., Laska, J., Biliński, K., Kulbacka, J., & Jankowska‐Konsur, A. (2025) · Dermatology and Therapy · doi:10.1007/s13555-025-01511-1 · Cited by 7 · see citing works
The effect of lidocaine on PpIX photobleaching and outcome of ALA-PDT in vitro
Mikolajewska, P., Juzeniene, A., & Moan, J. E. (2007) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2007.10.002 · Cited by 7 · see citing works
Effect of (R)L-sulforaphane on 5-aminolevulinic acid-mediated photodynamic therapy
Mikolajewska, P., Juzeniene, A., & Moan, J. E. (2008) · Translational research · doi:10.1016/j.trsl.2008.07.004 · Cited by 6 · see citing works
- Authors
- Wiegell, S. R.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Wiegell, Stine Regin
- ORCID
- Wiegell, Stine Regin
- Venue
- Archives of Dermatology
- Publisher
- American Medical Association (AMA)
- Published
- 2003-09-01
- Volume
- 139
- Issue
- 9
- Pages
- 1173
- ISSN
- 0003-987X (ISSN-L)
- OpenAlex
- W1990293009
- Cited by
- 142
- References
- 16
- Citations by year
- 2025: 7 · 2024: 3 · 2022: 2 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 8 · 2015: 8 · 2014: 4 · 2013: 4 · 2012: 6
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Keywords
- photodynamic therapy, 5-aminolevulinic acid, tape stripping, protoporphyrin IX fluorescence, erythema, skin pigmentation, GABA receptors, peripheral nerve pain
- MeSH terms
- Adult, Aminolevulinic Acid, Double-Blind Method, Esterification, Female, Humans, Male, Methyl Ethers, Pain, Pain Measurement, Photochemotherapy, Reference Values, Time Factors, Photosensitizing Agents
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