Rapid optical control of nociception with an ion-channel photoswitch

Alexandre Mourot, Timm Fehrentz, Yves Le Feuvre, Caleb M. Smith, Christian Herold, Deniz Dalkara, Frédéric Nagy, Dirk Trauner, Richard H. Kramer

Research output: Contribution to journalArticle

Abstract

Local anesthetics effectively suppress pain sensation, but most of these compounds act nonselectively, inhibiting activity of all neurons. Moreover, their actions abate slowly, preventing precise spatial and temporal control of nociception. We developed a photoisomerizable molecule, quaternary ammonium-azobenzene-quaternary ammonium (QAQ), that enables rapid and selective optical control of nociception. QAQ is membrane-impermeant and has no effect on most cells, but it infiltrates pain-sensing neurons through endogenous ion channels that are activated by noxious stimuli, primarily TRPV1. After QAQ accumulates intracellularly, it blocks voltage-gated ion channels in the trans form but not the cis form. QAQ enables reversible optical silencing of mouse nociceptive neuron firing without exogenous gene expression and can serve as a light-sensitive analgesic in rats in vivo. Because intracellular QAQ accumulation is a consequence of nociceptive ion-channel activity, QAQ-mediated photosensitization is a platform for understanding signaling mechanisms in acute and chronic pain.

Original languageEnglish (US)
Pages (from-to)396-402
Number of pages7
JournalNature Methods
Volume9
Issue number4
DOIs
StatePublished - Apr 2012

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Nociception
Ion Channels
Ammonium Compounds
Neurons
Photosensitivity Disorders
Pain
Nociceptors
Acute Pain
Local Anesthetics
Gene expression
Chronic Pain
Analgesics
azobenzene
Rats

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology
  • Biochemistry
  • Cell Biology

Cite this

Mourot, A., Fehrentz, T., Le Feuvre, Y., Smith, C. M., Herold, C., Dalkara, D., ... Kramer, R. H. (2012). Rapid optical control of nociception with an ion-channel photoswitch. Nature Methods, 9(4), 396-402. https://doi.org/10.1038/nmeth.1897

Rapid optical control of nociception with an ion-channel photoswitch. / Mourot, Alexandre; Fehrentz, Timm; Le Feuvre, Yves; Smith, Caleb M.; Herold, Christian; Dalkara, Deniz; Nagy, Frédéric; Trauner, Dirk; Kramer, Richard H.

In: Nature Methods, Vol. 9, No. 4, 04.2012, p. 396-402.

Research output: Contribution to journalArticle

Mourot, A, Fehrentz, T, Le Feuvre, Y, Smith, CM, Herold, C, Dalkara, D, Nagy, F, Trauner, D & Kramer, RH 2012, 'Rapid optical control of nociception with an ion-channel photoswitch', Nature Methods, vol. 9, no. 4, pp. 396-402. https://doi.org/10.1038/nmeth.1897
Mourot A, Fehrentz T, Le Feuvre Y, Smith CM, Herold C, Dalkara D et al. Rapid optical control of nociception with an ion-channel photoswitch. Nature Methods. 2012 Apr;9(4):396-402. https://doi.org/10.1038/nmeth.1897
Mourot, Alexandre ; Fehrentz, Timm ; Le Feuvre, Yves ; Smith, Caleb M. ; Herold, Christian ; Dalkara, Deniz ; Nagy, Frédéric ; Trauner, Dirk ; Kramer, Richard H. / Rapid optical control of nociception with an ion-channel photoswitch. In: Nature Methods. 2012 ; Vol. 9, No. 4. pp. 396-402.
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