Inhibition of the kinase WNK1/HSN2 ameliorates neuropathic pain by restoring GABA inhibition

Kristopher T. Kahle; Jean-François Schmouth; Valérie Lavastre; Alban Latremoliere; Jinwei Zhang; Nick Andrews; Takao Omura; Janet Laganière; Daniel Rochefort; Pascale Hince; Geneviève Castonguay; Rébecca Gaudet; Josiane C. S. Mapplebeck; Susana G. Sotocinal; JingJing Duan; Catherine Ward; Arjun R. Khanna; Jeffrey S. Mogil; Patrick A. Dion; Clifford J. Woolf; Perrine Inquimbert; Guy A. Rouleau

doi:10.1126/scisignal.aad0163

Research ArticlePain

Inhibition of the kinase WNK1/HSN2 ameliorates neuropathic pain by restoring GABA inhibition

Kristopher T. Kahle¹,²,*,†,‡,
Jean-François Schmouth³,⁴,†,
Valérie Lavastre³,⁴,†,
Alban Latremoliere⁵,
Jinwei Zhang⁶,
Nick Andrews⁵,
Takao Omura⁵,
Janet Laganière³,⁴,
Daniel Rochefort³,⁴,
Pascale Hince³,
Geneviève Castonguay³,
Rébecca Gaudet³,
Josiane C. S. Mapplebeck⁷,
Susana G. Sotocinal⁷,
JingJing Duan¹,
Catherine Ward⁵,
Arjun R. Khanna²,
Jeffrey S. Mogil⁷,
Patrick A. Dion³,⁴,
Clifford J. Woolf⁵,
Perrine Inquimbert⁸, and
Guy A. Rouleau³,⁴,*

¹Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
²Department of Neurosurgery, Boston Children’s Hospital, Boston, MA 02124, USA.
³Montreal Neurological Institute and Hospital, McGill University, Montréal, Quebec H3A 2B4, Canada.
⁴Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec H3A 2B4, Canada.
⁵F.M. Kirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
⁶MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
⁷Department of Psychology and Centre for Research on Pain, McGill University, Montréal, Quebec H3A 0G1, Canada.
⁸Institut des Neurosciences Cellulaires et Integratives, UPR 3212 Centre National de la Recherche Scientifique, and Universite de Strasbourg, 5 rue Blaise Pascal, F-67084 Strasbourg, France.

↵*Corresponding author. E-mail: guy.rouleau{at}mcgill.ca (G.A.R.); kristopher.kahle{at}yale.edu (K.T.K.)

↵† These authors contributed equally to this work.
↵‡ Present address: Departments of Neurosurgery, Pediatrics, and Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06511, USA.

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Science Signaling 29 Mar 2016:
Vol. 9, Issue 421, pp. ra32
DOI: 10.1126/scisignal.aad0163

Kristopher T. Kahle

1Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.

2Department of Neurosurgery, Boston Children’s Hospital, Boston, MA 02124, USA.

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For correspondence: guy.rouleau@mcgill.ca kristopher.kahle@yale.edu

Jean-François Schmouth

3Montreal Neurological Institute and Hospital, McGill University, Montréal, Quebec H3A 2B4, Canada.

4Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec H3A 2B4, Canada.

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Valérie Lavastre

3Montreal Neurological Institute and Hospital, McGill University, Montréal, Quebec H3A 2B4, Canada.

4Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec H3A 2B4, Canada.

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Alban Latremoliere

5F.M. Kirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.

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Jinwei Zhang

6MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.

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Nick Andrews

5F.M. Kirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.

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Takao Omura

5F.M. Kirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.

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Janet Laganière

3Montreal Neurological Institute and Hospital, McGill University, Montréal, Quebec H3A 2B4, Canada.

4Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec H3A 2B4, Canada.

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Daniel Rochefort

3Montreal Neurological Institute and Hospital, McGill University, Montréal, Quebec H3A 2B4, Canada.

4Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec H3A 2B4, Canada.

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Pascale Hince

3Montreal Neurological Institute and Hospital, McGill University, Montréal, Quebec H3A 2B4, Canada.

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Geneviève Castonguay

3Montreal Neurological Institute and Hospital, McGill University, Montréal, Quebec H3A 2B4, Canada.

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Rébecca Gaudet

3Montreal Neurological Institute and Hospital, McGill University, Montréal, Quebec H3A 2B4, Canada.

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Josiane C. S. Mapplebeck

7Department of Psychology and Centre for Research on Pain, McGill University, Montréal, Quebec H3A 0G1, Canada.

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Susana G. Sotocinal

7Department of Psychology and Centre for Research on Pain, McGill University, Montréal, Quebec H3A 0G1, Canada.

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JingJing Duan

1Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.

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Catherine Ward

5F.M. Kirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.

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Arjun R. Khanna

2Department of Neurosurgery, Boston Children’s Hospital, Boston, MA 02124, USA.

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Jeffrey S. Mogil

7Department of Psychology and Centre for Research on Pain, McGill University, Montréal, Quebec H3A 0G1, Canada.

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Patrick A. Dion

3Montreal Neurological Institute and Hospital, McGill University, Montréal, Quebec H3A 2B4, Canada.

4Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec H3A 2B4, Canada.

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Clifford J. Woolf

5F.M. Kirby Neurobiology Center, Boston Children’s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.

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Perrine Inquimbert

8Institut des Neurosciences Cellulaires et Integratives, UPR 3212 Centre National de la Recherche Scientifique, and Universite de Strasbourg, 5 rue Blaise Pascal, F-67084 Strasbourg, France.

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Guy A. Rouleau

3Montreal Neurological Institute and Hospital, McGill University, Montréal, Quebec H3A 2B4, Canada.

4Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec H3A 2B4, Canada.

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For correspondence: guy.rouleau@mcgill.ca kristopher.kahle@yale.edu

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