title: Role of Prelimbic GABAergic Circuits in Sensory and Emotional Aspects of Neuropathic Pain.
abstract: Noxious stimuli are detected by peripheral nociceptors and then transmitted to higher CNS centers, where they are perceived as an unpleasant sensation. The mechanisms that govern the emotional component associated with pain are still incompletely understood. Here, we used optogenetic approaches both in vitro and in vivo to address this issue. We found that peripheral nerve injury inhibits pyramidal cell firing in the prelimbic area of the prefrontal cortex as a result of feed-forward inhibition mediated by parvalbumin-expressing GABAergic interneurons. In addition, activation of inhibitory archaerhodopsin or excitatory channelrhodopsin-2 in these neurons decreased and increased pain responses, respectively, in freely moving mice and accordingly modulated conditioned place preference scores and place escape/avoidance behavior. Our findings thus demonstrate an important role of the prelimbic area in sensory and emotional aspects of pain and identify GABAergic circuits in this region as a potential target for pain therapeutics.
authors.affiliation: Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Vinicius M
authors.initials: VM
authors.lastname: Gadotti
authors.affiliation: Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Lina
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Ivana A
authors.initials: IA
authors.lastname: Souza
authors.affiliation: Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Stemkowski
authors.affiliation: Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada. Electronic address: zamponi@ucalgary.ca.
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Zamponi
mesh_terms: D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D004644:Emotions; D059330:GABAergic Neurons; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009437:Neuralgia / Q000235:genetics / Q000503:physiopathology*; D017966:Pyramidal Cells