title: Epidural optogenetics for controlled analgesia.
abstract: BACKGROUND
  Optogenetic tools enable cell selective and temporally precise control of neuronal activity; yet, difficulties in delivering sufficient light to the spinal cord of freely behaving animals have hampered the use of spinal optogenetic approaches to produce analgesia. We describe an epidural optic fiber designed for chronic spinal optogenetics that enables the precise delivery of light at multiple wavelengths to the spinal cord dorsal horn and sensory afferents.
  
  
  RESULTS
  The epidural delivery of light enabled the optogenetic modulation of nociceptive processes at the spinal level. The acute and repeated activation of channelrhodopsin-2 expressing nociceptive afferents produced robust nocifensive behavior and mechanical sensitization in freely behaving mice, respectively. The optogenetic inhibition of GABAergic interneurons in the spinal cord dorsal horn through the activation of archaerhodopsin also produced a transient, but selective induction of mechanical hypersensitivity. Finally, we demonstrate the capacity of optogenetics to produce analgesia in freely behaving mice through the inhibition of nociceptive afferents via archaerhodopsin.
  
  
  CONCLUSIONS
  Epidural optogenetics provides a robust and powerful solution for activation of both excitatory and inhibitory opsins in sensory processing pathways. Our results demonstrate the potential of spinal optogenetics to modulate sensory behavior and produce analgesia in freely behaving animals.
authors.affiliation: Institut Universitaire en santé mentale de Québec, Québec, Canada.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Bonin
authors.affiliation: Institut Universitaire en santé mentale de Québec, Québec, Canada.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Institut Universitaire en santé mentale de Québec, Québec, Canada.
authors.forename: Mireille
authors.initials: M
authors.lastname: Desrochers-Couture
authors.affiliation: Department of Physics, Université Laval, Québec, Canada.
authors.forename: Alicja
authors.initials: A
authors.lastname: Ga Secka
authors.affiliation: Institut Universitaire en santé mentale de Québec, Québec, Canada.
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Boulanger
authors.affiliation: Department of Physics, Université Laval, Québec, Canada.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Côté
authors.affiliation: Institut Universitaire en santé mentale de Québec, Québec, Canada Department of Psychiatry and Neuroscience, Université Laval, Québec, Canada yves.dekoninck@neuro.ulaval.ca.
authors.forename: Yves
authors.initials: Y
authors.lastname: De Koninck
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D015360:Analgesia, Epidural; D000818:Animals; D008297:Male; D008810:Mice, Inbred C57BL; D059225:Nociception; D055355:Opsins / Q000378:metabolism; D055100:Optical Fibers; D062308:Optogenetics / Q000379:methods*; D011984:Sensory Receptor Cells / Q000502:physiology
chemical_list: D055355:Opsins
keywords: Optogenetics; allodynia; analgesia; dorsal horn; hyperalgesia; optics; pain; plasticity; spinal cord