Optogenetic and chemogenetic strategies for sustained inhibition of pain

Spatially targeted, genetically-specific strategies for sustained inhibition of nociceptors may help transform pain science and clinical management. Previous optogenetic strategies to inhibit pain have required constant illumination and chemogenetic approaches in the periphery have not been shown to...

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Bibliographic Details
Published in:Scientific reports 2016-08, Vol.6 (1), p.30570-30570, Article 30570
Main Authors: Iyer, Shrivats M., Vesuna, Sam, Ramakrishnan, Charu, Huynh, Karen, Young, Stephanie, Berndt, Andre, Lee, Soo Yeun, Gorini, Christopher J., Deisseroth, Karl, Delp, Scott L.
Format: Article
Language:English
Subjects:
631/378/1689/2610
631/378/1959/2605
631/378/3917
692/617/375/430
Animals
Cells, Cultured
Channelrhodopsins - genetics
Clozapine - administration & dosage
Clozapine - analogs & derivatives
Clozapine - therapeutic use
Combined Modality Therapy
Disease Models, Animal
Humanities and Social Sciences
Illumination
Low-Level Light Therapy
Mice
multidisciplinary
Nociception
Nociceptors
Optogenetics - methods
Pain
Pain - drug therapy
Pain - radiotherapy
Pain perception
Science
Sensory neurons
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Summary:Spatially targeted, genetically-specific strategies for sustained inhibition of nociceptors may help transform pain science and clinical management. Previous optogenetic strategies to inhibit pain have required constant illumination and chemogenetic approaches in the periphery have not been shown to inhibit pain. Here, we show that the step-function inhibitory channelrhodopsin, SwiChR, can be used to persistently inhibit pain for long periods of time through infrequent transdermally delivered light pulses, reducing required light exposure by >98% and resolving a long-standing limitation in optogenetic inhibition. We demonstrate that the viral expression of the hM4D receptor in small-diameter primary afferent nociceptor enables chemogenetic inhibition of mechanical and thermal nociception thresholds. Finally, we develop optoPAIN, an optogenetic platform to non-invasively assess changes in pain sensitivity and use this technique to examine pharmacological and chemogenetic inhibition of pain.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep30570