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Photosensitization in porphyrias and photodynamic therapy involves TRPA1 and TRPV1

Babes, Alexandru; Sauer, Susanne K.; Moparthi, Lavanya LU ; Kichko, Tatjana I.; Neacsu, Cristian; Namer, Barbara; Filipovic, Milos; Zygmunt, Peter M. LU ; Reeh, Peter W. and Fischer, Michael J M (2016) In Journal of Neuroscience 36(19). p.5264-5278
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aminolaevulinic acid, Pain, Protoporphyrin IX
in
Journal of Neuroscience
volume
36
issue
19
pages
15 pages
publisher
Society for Neuroscience
external identifiers
  • scopus:84966473894
  • wos:000378279500009
ISSN
0270-6474
DOI
10.1523/JNEUROSCI.4268-15.2016
language
English
LU publication?
yes
id
7ebf74b7-8de9-41c4-923b-82ae60e7ed07
date added to LUP
2016-09-28 11:01:17
date last changed
2017-06-11 05:08:49
@article{7ebf74b7-8de9-41c4-923b-82ae60e7ed07,
  abstract     = {<p>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.</p>},
  author       = {Babes, Alexandru and Sauer, Susanne K. and Moparthi, Lavanya and Kichko, Tatjana I. and Neacsu, Cristian and Namer, Barbara and Filipovic, Milos and Zygmunt, Peter M. and Reeh, Peter W. and Fischer, Michael J M},
  issn         = {0270-6474},
  keyword      = {Aminolaevulinic acid,Pain,Protoporphyrin IX},
  language     = {eng},
  month        = {05},
  number       = {19},
  pages        = {5264--5278},
  publisher    = {Society for Neuroscience},
  series       = {Journal of Neuroscience},
  title        = {Photosensitization in porphyrias and photodynamic therapy involves TRPA1 and TRPV1},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.4268-15.2016},
  volume       = {36},
  year         = {2016},
}