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Nat Biotechnol. 2014 Mar;32(3):274-8. doi: 10.1038/nbt.2834. Epub 2014 Feb 16.

Virally mediated optogenetic excitation and inhibition of pain in freely moving nontransgenic mice.

Author information

1
1] Department of Bioengineering, Stanford University, Stanford, California, USA. [2].
2
Department of Bioengineering, Stanford University, Stanford, California, USA.
3
1] Department of Bioengineering, Stanford University, Stanford, California, USA. [2] Howard Hughes Medical Institute, Stanford University, Stanford, California, USA.
4
1] Department of Bioengineering, Stanford University, Stanford, California, USA. [2] Department of Mechanical Engineering, Stanford University, Stanford, California, USA.

Abstract

Primary nociceptors are the first neurons involved in the complex processing system that regulates normal and pathological pain. Because of constraints on pharmacological and electrical stimulation, noninvasive excitation and inhibition of these neurons in freely moving nontransgenic animals has not been possible. Here we use an optogenetic strategy to bidirectionally control nociceptors of nontransgenic mice. Intrasciatic nerve injection of adeno-associated viruses encoding an excitatory opsin enabled light-inducible stimulation of acute pain, place aversion and optogenetically mediated reductions in withdrawal thresholds to mechanical and thermal stimuli. In contrast, viral delivery of an inhibitory opsin enabled light-inducible inhibition of acute pain perception, and reversed mechanical allodynia and thermal hyperalgesia in a model of neuropathic pain. Light was delivered transdermally, allowing these behaviors to be induced in freely moving animals. This approach may have utility in basic and translational pain research, and enable rapid drug screening and testing of newly engineered opsins.

Comment in

PMID:
24531797
PMCID:
PMC3988230
DOI:
10.1038/nbt.2834
[Indexed for MEDLINE]
Free PMC Article

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