Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury
Hugues Petitjean,
Sophie Anne Pawlowski,
Steven Li Fraine,
Behrang Sharif,
Doulia Hamad,
Tarheen Fatima,
Jim Berg,
Claire M. Brown,
Lily-Yeh Jan,
Alfredo Ribeiro-da-Silva,
Joao M. Braz,
Allan I. Basbaum,
Reza Sharif-Naeini
Affiliations
Hugues Petitjean
Department of Physiology and Cell Information Systems Group, McGill University, Montreal, H3G0B1 QC, Canada
Sophie Anne Pawlowski
Department of Pharmacology and Therapeutics, McGill University, H3G1Y6 QC, Canada
Steven Li Fraine
Department of Physiology and Cell Information Systems Group, McGill University, Montreal, H3G0B1 QC, Canada
Behrang Sharif
Department of Physiology and Cell Information Systems Group, McGill University, Montreal, H3G0B1 QC, Canada
Doulia Hamad
Department of Physiology and Cell Information Systems Group, McGill University, Montreal, H3G0B1 QC, Canada
Tarheen Fatima
Department of Physiology and Cell Information Systems Group, McGill University, Montreal, H3G0B1 QC, Canada
Jim Berg
Departments of Physiology and Biochemistry, Howard Hughes Medical Institute, University of California, San Francisco, 1550 4th Street, RH-490D, San Francisco, CA 94158, USA
Claire M. Brown
Department of Physiology and Cell Information Systems Group, McGill University, Montreal, H3G0B1 QC, Canada
Lily-Yeh Jan
Departments of Physiology and Biochemistry, Howard Hughes Medical Institute, University of California, San Francisco, 1550 4th Street, RH-490D, San Francisco, CA 94158, USA
Alfredo Ribeiro-da-Silva
Department of Pharmacology and Therapeutics, McGill University, H3G1Y6 QC, Canada
Joao M. Braz
Department of Anatomy, University of California, San Francisco, 1550 4th Street, RH-348E, San Francisco, CA 94158, USA
Allan I. Basbaum
Department of Anatomy, University of California, San Francisco, 1550 4th Street, RH-348E, San Francisco, CA 94158, USA
Reza Sharif-Naeini
Department of Physiology and Cell Information Systems Group, McGill University, Montreal, H3G0B1 QC, Canada
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.
