It has been speculated that topical application of 5-aminolevulinic acid (ALA) or methyl 5-aminolevulinate (MAL) may
be more painful during light exposure after longer application times of the compounds than after shorter times, even
though the same levels of protoporphyrin IX (PpIX) is produced in both cases.
The aim of our study was to investigate pain induction in the build-up and clearance phases of PpIX in the skin of
healthy volunteers. 0.6 mmol/g of ALA (10% wt/wt) and MAL (11% wt/wt) creams were applied on the volunteers. The
creams were maintained on the spots for 20- 24 hours and then wiped off. Subsequently, fresh creams were applied on
the other arm of the volunteers for 4- 6 hours. Fluorescence emission spectra for all spots were measured every hour until
the fluorescence levels were similar in both arms for ALA and MAL. Then the test areas were exposed to light until pain
occurred. Time for pain to occur was recorded. The fluorescence of PpIX was measured before and after light exposure.
PDT in the clearance phase seems to induce pain faster than in the build-up phase for ALA and MAL. Due to large
interpersonal variations between volunteers further investigation is needed.