Cause of Pain of Photodynamic Therapy Identified

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Exaggerated sensitivity to harmless light, or photosensitization, is often triggered by dermatologists using photodynamic therapy to treat precancerous skin lesions and skin cancers. This study examined the underlying molecular transduction mechanism and identified potential targets for addressing the severe pain some patients experience.1

Photodynamic therapy is very effective, but it can also be extremely painful and cause inflammation that discourages patients from undergoing the therapy again if it is needed in other locations. The causes of the pain and inflammation were previously unknown.

An international team of researchers at Friedrich-Alexander University's Institute of Physiology and Pathophysiology, Bucharest, Romania, has found the cause. The team conducted a study with volunteers whose skin was exposed to a dark blue laser pointer.

The light from this type of laser pointer has exactly the right wave length to stimulate all cells to produce free radicals. When the laser pointer was directed at bare skin, participants began to feel a slight pinprick-like pain after approximately 30 seconds. However, when the cream used in photodynamic therapy was applied to the skin beforehand, the pain became much more intense, and none of the participants were able to withstand it for more than 40 seconds. When skin is treated with the cream, even the red light can cause severe burning pain. The red light is used for therapy because it has a longer wave length and so it penetrates the skin further.

The aggressive free oxygen radicals were found to be active both in diseased skin cells and also in certain nerve endings that recognize the early signs of damage. In the nerve cells the free radicals activate the ion channel TRPA1, which triggers pain or itching. When the cream is applied to skin, exposure to light triggers a second ion channel, TRPV1, which increases the pain. TRPV1 is known as the capsaicin receptor and is also what triggers the burning sensation caused by chilis. Both TRPA1 and TRPV1 are activated by the free oxygen radicals and stimulate the nerve endings, causing pain and inflammation as these nerves also release inflammatory substances called neuropeptides.

“Medications that block both ion channels have already been tested in the treatment of other types of pain, such as the pain experienced in diabetic neuropathy or arthritis,' explained coauthor Peter Reeh, PhD. “Based on the findings of this study, these should have 2 benefits in this case, as they would reduce both pain and inflammation.”


1. Babes A, Sauer SK, Moparthi L, et al. Photosensitization in porphyrias and photodynamic therapy involves TRPA1 and TRPV1. J Neurosci 2016;36(19):5264-5278.

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