title: Virally mediated optogenetic excitation and inhibition of pain in freely moving nontransgenic mice.
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.
authors: 1] Department of Bioengineering, Stanford University, Stanford, California, USA. [2].
authors: Shrivats Mohan
authors: SM
authors: Iyer
authors: 1] Department of Bioengineering, Stanford University, Stanford, California, USA. [2].
authors: Kate L
authors: KL
authors: Montgomery
authors: Department of Bioengineering, Stanford University, Stanford, California, USA.
authors: Chris
authors: C
authors: Towne
authors: Department of Bioengineering, Stanford University, Stanford, California, USA.
authors: Soo Yeun
authors: SY
authors: Lee
authors: Department of Bioengineering, Stanford University, Stanford, California, USA.
authors: Charu
authors: C
authors: Ramakrishnan
authors: 1] Department of Bioengineering, Stanford University, Stanford, California, USA. [2] Howard Hughes Medical Institute, Stanford University, Stanford, California, USA.
authors: Karl
authors: K
authors: Deisseroth
authors: 1] Department of Bioengineering, Stanford University, Stanford, California, USA. [2] Department of Mechanical Engineering, Stanford University, Stanford, California, USA.
authors: Scott L
authors: SL
authors: Delp
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000528:radiation effects; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D005818:Genetic Engineering / Q000379:methods; D015316:Genetic Therapy; D007267:Injections; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D009619:Nociceptors / Q000528:radiation effects*; D055355:Opsins / Q000235:genetics; D062308:Optogenetics / Q000379:methods*; D010146:Pain / Q000235:genetics* / Q000503:physiopathology; D012584:Sciatic Nerve / Q000502:physiology
chemical_list: D055355:Opsins