Background: Pain during topical aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) limits the use of this treatment of skin diseases.
Objective: We sought to summarize the effectiveness of interventions to reduce ALA-PDT-related pain, and to explore factors contributing to pain induction.
Methods: A PubMed search was performed to identify all clinical PDT trials (2000-2008) that used ALA or methyl-ALA, enrolled at least 10 patients per trial, and used a semiquantitative pain scale.
Results: In all, 43 articles were identified for review. Pain intensity is associated with lesion size and location and can be severe for certain diagnoses, such as plaque-type psoriasis. Results are inconsistent for the correlation of pain with light source, wavelength of light, fluence rate, and total light dose. Cooling represents the best topical intervention.
Limitations: Pain perception differs widely between patients and can contribute to variability in the reported results.
Conclusion: Gamma-aminobutyric acid receptors, cold/menthol receptors (transient receptor potential cation channel, subfamily M, member 8), and vanilloid/capsaicin receptors (transient receptor potential cation channel, subfamily V, member 1) may be involved in pain perception during ALA-PDT and are therefore worthy of further investigation.