Ketamine induces rapid and sustained antidepressant-like effects in chronic pain induced depression: Role of MAPK signaling pathway.

Autor: Humo M; Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique et Université de Strasbourg, 67000 Strasbourg, France., Ayazgök B; Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique et Université de Strasbourg, 67000 Strasbourg, France; Department of Biochemistry, Faculty of Pharmacy, University of Hacettepe, Ankara, Turkey., Becker LJ; Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique et Université de Strasbourg, 67000 Strasbourg, France., Waltisperger E; Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique et Université de Strasbourg, 67000 Strasbourg, France., Rantamäki T; Laboratory of Neurotherapeutics, Drug Research Program, Division of Pharmacology and Pharmacotherapeutics, Faculty of Pharmacy, University of Helsinki, Finland; SleepWell Research Program, Faculty of Medicine, University of Helsinki, Finland., Yalcin I; Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique et Université de Strasbourg, 67000 Strasbourg, France. Electronic address: yalcin@inci-cnrs.unistra.fr.
Jazyk: angličtina
Zdroj: Progress in neuro-psychopharmacology & biological psychiatry [Prog Neuropsychopharmacol Biol Psychiatry] 2020 Jun 08; Vol. 100, pp. 109898. Date of Electronic Publication: 2020 Feb 25.
DOI: 10.1016/j.pnpbp.2020.109898
Abstrakt: Chronic pain produces psychologic distress, which often leads to mood disorders such as depression. Co-existing chronic pain and depression pose a serious socio-economic burden and result in disability affecting millions of individuals, which urges the development of treatment strategies targeting this comorbidity. Ketamine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, is shown to be efficient in treating both pain and depression-related symptoms. However, the molecular characteristics of its role in chronic pain-induced depression remain largely unexplored. Hence, we studied the behavioral and molecular effects of a single systemic administration of ketamine (15 mg/kg, i.p.) on mechanical hypersensitivity and depressive-like consequences of chronic neuropathic pain. We showed that ketamine transiently alleviated mechanical hypersensitivity (lasting <24 h), while its antidepressant effect was observed even 72 h after administration. In addition, ketamine normalized the upregulated expression of the mitogen activated protein kinase (MAPK) phosphatase 1 (MKP-1) and the downregulated phosphorylation of extracellular signal-regulated kinase (pERK) in the anterior cingulate cortex (ACC) of mice displaying neuropathic pain-induced depressive-like behaviors. This effect of ketamine on the MKP-1 was first detected 30 min after the ketamine administration and persisted until up to 72 h. Altogether, these findings provide insight into the behavioral and molecular changes associated with single ketamine administration in the comorbidity of chronic pain and depression.
Competing Interests: Declaration of Competing Interest None. The authors declare that they have no conflict of interest. The funding sources had no role in the study design, in the interpretation of data and in the writing of the manuscript.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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