Photosensitization in porphyrias and photodynamic therapy involves TRPA1 and TRPV1

Research output: Contribution to journalArticle

Abstract

Photosensitization, an exaggerated sensitivity to harmless light, occurs genetically in rare diseases, such as porphyrias, and in photodynamic therapy where short-term toxicity is intended. A common feature is the experience of pain from bright light. In human subjects, skin exposure to 405 nm light induced moderate pain, which was intensified by pretreatment with aminolevulinic acid. In heterologous expression systems and cultured sensory neurons, exposure to blue light activated TRPA1 and, to a lesser extent, TRPV1 channels in the absence of additional photosensitization. Pretreatment with aminolevulinic acid or with protoporphyrin IX dramatically increased the light sensitivity of both TRPA1 and TRPV1 via generation of reactive oxygen species. Artificial lipid bilayers equipped with purified human TRPA1 showed substantial single-channel activity only in the presence of protoporphyrin IX and blue light. Photosensitivity and photosensitization could be demonstrated in freshly isolated mouse tissues and led to TRP channel-dependent release of proinflammatory neuropeptides upon illumination. With antagonists in clinical development, these findings may help to alleviate pain during photodynamic therapy and also allow for disease modification in porphyria patients.

Details

Authors
  • Alexandru Babes
  • Susanne K. Sauer
  • Lavanya Moparthi
  • Tatjana I. Kichko
  • Cristian Neacsu
  • Barbara Namer
  • Milos Filipovic
  • Peter M. Zygmunt
  • Peter W. Reeh
  • Michael J M Fischer
Organisations
External organisations
  • Friedrich-Alexander University Erlangen-Nürnberg
  • University of Bucharest
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • Aminolaevulinic acid, Pain, Protoporphyrin IX
Original languageEnglish
Pages (from-to)5264-5278
Number of pages15
JournalJournal of Neuroscience
Volume36
Issue number19
Publication statusPublished - 2016 May 11
Publication categoryResearch
Peer-reviewedYes