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Photosensitization in porphyrias and photodynamic therapy involves TRPA1 and TRPV1

In English

Författare

  • 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

Summary, in English

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.

Publiceringsår

2016-05-11

Språk

Engelska

Sidor

5264-5278

Publikation/Tidskrift/Serie

The Journal of Neuroscience

Volym

36

Issue

19

Dokumenttyp

Artikel i tidskrift

Förlag

Society for Neuroscience

Ämne

  • Neurology

Nyckelord

  • Aminolaevulinic acid
  • Pain
  • Protoporphyrin IX

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 0270-6474