title: Identification of spinal circuits transmitting and gating mechanical pain.
abstract: Pain information processing in the spinal cord has been postulated to rely on nociceptive transmission (T) neurons receiving inputs from nociceptors and Aβ mechanoreceptors, with Aβ inputs gated through feed-forward activation of spinal inhibitory neurons (INs). Here, we used intersectional genetic manipulations to identify these critical components of pain transduction. Marking and ablating six populations of spinal excitatory and inhibitory neurons, coupled with behavioral and electrophysiological analysis, showed that excitatory neurons expressing somatostatin (SOM) include T-type cells, whose ablation causes loss of mechanical pain. Inhibitory neurons marked by the expression of dynorphin (Dyn) represent INs, which are necessary to gate Aβ fibers from activating SOM(+) neurons to evoke pain. Therefore, peripheral mechanical nociceptors and Aβ mechanoreceptors, together with spinal SOM(+) excitatory and Dyn(+) inhibitory neurons, form a microcircuit that transmits and gates mechanical pain. PAPERCLIP:
authors.affiliation: Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Duan
authors.affiliation: Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA.|Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
authors.forename: Longzhen
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Steeve
authors.initials: S
authors.lastname: Bourane
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Britz
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Padilla
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Lidia
authors.initials: L
authors.lastname: Garcia-Campmany
authors.affiliation: Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Ave., Boston, Massachusetts 02215.|Present address: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA and National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Krashes
authors.affiliation: Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Knowlton
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Velasquez
authors.affiliation: Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Neurobiology and University of Pittsburgh Pain Center, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ross
authors.affiliation: Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Ave., Boston, Massachusetts 02215.
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
authors.affiliation: Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Martyn
authors.initials: M
authors.lastname: Goulding
authors.affiliation: Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA.
authors.forename: Qiufu
authors.initials: Q
authors.lastname: Ma
mesh_terms: D000818:Animals; D004399:Dynorphins / Q000378:metabolism; D008465:Mechanoreceptors / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000502:physiology*; D010146:Pain / Q000378:metabolism*; D058748:Pain Perception; D013004:Somatostatin / Q000378:metabolism; D013116:Spinal Cord / Q000502:physiology*
chemical_list: D013004:Somatostatin; D004399:Dynorphins