title: Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury.
abstract: Neuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to neuropathic pain, the molecular and cellular mechanisms underlying this disinhibition are unclear. Here, we combined pharmacogenetic activation and selective ablation approaches in mice to define the contribution of spinal cord parvalbumin (PV)-expressing inhibitory interneurons in naive and neuropathic pain conditions. Ablating PV neurons in naive mice produce neuropathic pain-like mechanical allodynia via disinhibition of PKCγ excitatory interneurons. Conversely, activating PV neurons in nerve-injured mice alleviates mechanical hypersensitivity. These findings indicate that PV interneurons are modality-specific filters that gate mechanical but not thermal inputs to the dorsal horn and that increasing PV interneuron activity can ameliorate the mechanical hypersensitivity that develops following nerve injury.
authors.affiliation: Department of Physiology and Cell Information Systems Group, McGill University, Montreal, H3G0B1 QC, Canada.
authors.forename: Hugues
authors.initials: H
authors.lastname: Petitjean
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, H3G1Y6 QC, Canada.
authors.forename: Sophie Anne
authors.initials: SA
authors.lastname: Pawlowski
authors.affiliation: Department of Physiology and Cell Information Systems Group, McGill University, Montreal, H3G0B1 QC, Canada.
authors.forename: Steven Li
authors.initials: SL
authors.lastname: Fraine
authors.affiliation: Department of Physiology and Cell Information Systems Group, McGill University, Montreal, H3G0B1 QC, Canada.
authors.forename: Behrang
authors.initials: B
authors.lastname: Sharif
authors.affiliation: Department of Physiology and Cell Information Systems Group, McGill University, Montreal, H3G0B1 QC, Canada.
authors.forename: Doulia
authors.initials: D
authors.lastname: Hamad
authors.affiliation: Department of Physiology and Cell Information Systems Group, McGill University, Montreal, H3G0B1 QC, Canada.
authors.forename: Tarheen
authors.initials: T
authors.lastname: Fatima
authors.affiliation: Departments of Physiology and Biochemistry, Howard Hughes Medical Institute, University of California, San Francisco, 1550 4th Street, RH-490D, San Francisco, CA 94158, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Berg
authors.affiliation: Department of Physiology and Cell Information Systems Group, McGill University, Montreal, H3G0B1 QC, Canada; Advanced BioImaging Facility, McGill University, H3G0B1 QC, Canada.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Brown
authors.affiliation: Departments of Physiology and Biochemistry, Howard Hughes Medical Institute, University of California, San Francisco, 1550 4th Street, RH-490D, San Francisco, CA 94158, USA.
authors.forename: Lily-Yeh
authors.initials: LY
authors.lastname: Jan
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, H3G1Y6 QC, Canada; Department of Anatomy and Cell Biology, McGill University, H3A0C7 QC, Canada.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ribeiro-da-Silva
authors.affiliation: Department of Anatomy, University of California, San Francisco, 1550 4th Street, RH-348E, San Francisco, CA 94158, USA.
authors.forename: Joao M
authors.initials: JM
authors.lastname: Braz
authors.affiliation: Department of Anatomy, University of California, San Francisco, 1550 4th Street, RH-348E, San Francisco, CA 94158, USA.
authors.forename: Allan I
authors.initials: AI
authors.lastname: Basbaum
authors.affiliation: Department of Physiology and Cell Information Systems Group, McGill University, Montreal, H3G0B1 QC, Canada. Electronic address: reza.sharif@mcgill.ca.
authors.forename: Reza
authors.initials: R
authors.lastname: Sharif-Naeini
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006930:Hyperalgesia / Q000473:pathology / Q000503:physiopathology*; D007395:Interneurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D051379:Mice; D009437:Neuralgia / Q000473:pathology / Q000503:physiopathology*; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D066148:Spinal Cord Dorsal Horn / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism / Q000502:physiology; D014110:Touch
chemical_list: D010320:Parvalbumins; C087857:protein kinase C gamma; D011493:Protein Kinase C