title: Pain inhibition by optogenetic activation of specific anterior cingulate cortical neurons.
abstract: Cumulative evidence from both humans and animals suggests that the anterior cingulate cortex (ACC) is important for pain-related perception, and thus a likely target for pain relief therapy. However, use of existing electrode based ACC stimulation has not significantly reduced pain, at least in part due to the lack of specificity and likely co-activation of both excitatory and inhibitory neurons. Herein, we report a dramatic reduction of pain behavior in transgenic mice by optogenetic stimulation of the inhibitory neural circuitry of the ACC expressing channelrhodopsin-2. Electrophysiological measurements confirmed that stimulation of ACC inhibitory neurons is associated with decreased neural activity in the ACC. Further, a distinct optogenetic stimulation intensity and frequency-dependent inhibition of spiking activity in the ACC was observed. Moreover, we confirmed specific electrophysiological responses from different neuronal units in the thalamus, in response to particular types of painful stimuli (i,e., formalin injection, pinch), which we found to be modulated by optogenetic control of the ACC inhibitory neurons. These results underscore the inhibition of the ACC as a clinical alternative in inhibiting chronic pain, and leads to a better understanding of the pain processing circuitry of the cingulate cortex.
authors.affiliation: Biophysics and Physiology Group, Department of Physics, University of Texas at Arlington, Arlington, TX-76019, United States of America.
authors.forename: Ling
authors.initials: L
authors.lastname: Gu
authors.affiliation: Department of Psychology, University of Texas at Arlington, Arlington, TX-76019, United States of America.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Uhelski
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, Arlington, TX-76019, United States of America.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Anand
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, Arlington, TX-76019, United States of America.
authors.forename: Mario
authors.initials: M
authors.lastname: Romero-Ortega
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, Arlington, TX-76019, United States of America.
authors.forename: Young-tae
authors.initials: YT
authors.lastname: Kim
authors.affiliation: Departments of Psychology and Biology, University of Texas at Arlington, Arlington, TX-76019, United States of America.
authors.forename: Perry N
authors.initials: PN
authors.lastname: Fuchs
authors.affiliation: Biophysics and Physiology Group, Department of Physics, University of Texas at Arlington, Arlington, TX-76019, United States of America.
authors.forename: Samarendra K
authors.initials: SK
authors.lastname: Mohanty
mesh_terms: D000818:Animals; D000075402:Channelrhodopsins; D059350:Chronic Pain; D055724:Electrophysiological Phenomena; D015870:Gene Expression; D006179:Gyrus Cinguli / Q000502:physiology*; D007834:Lasers; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics; D010146:Pain; D010812:Physical Stimulation; D013788:Thalamus / Q000502:physiology
chemical_list: D000075402:Channelrhodopsins