Tianeptine promotes lasting antiallodynic effects in a mouse model of neuropathic pain.

Autor: Serafini RA; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Pharmacology, Physiology and Biophysics, Chobanian & Avedisian School of Medicine at Boston University, Boston, MA, USA., Estill M; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Pekarskaya EA; Department of Neuroscience, Columbia University, New York, NY, USA.; Department of Psychiatry, Columbia University, New York, NY, USA.; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA., Sakloth F; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Shen L; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Javitch JA; Department of Psychiatry, Columbia University, New York, NY, USA.; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA.; Department of Molecular Pharmacology and Therapeutics, Columbia University, New York, NY, USA., Zachariou V; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. vzachar@bu.edu.; Department of Pharmacology, Physiology and Biophysics, Chobanian & Avedisian School of Medicine at Boston University, Boston, MA, USA. vzachar@bu.edu.
Jazyk: angličtina
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2023 Oct; Vol. 48 (11), pp. 1680-1689. Date of Electronic Publication: 2023 Jul 20.
DOI: 10.1038/s41386-023-01645-w
Abstrakt: Tricyclic antidepressants (TCAs), such as desipramine (DMI), are effective at managing neuropathic pain symptoms but often take several weeks to become effective and also lead to considerable side effects. Tianeptine (TIAN) is an atypical antidepressant that activates the mu-opioid receptor but does not produce analgesic tolerance or withdrawal in mice, nor euphoria in humans, at clinically-relevant doses. Here, we evaluate the efficacy of TIAN at persistently alleviating mechanical allodynia in the spared nerve injury (SNI) model of neuropathic pain, even well after drug clearance. After finding an accelerated onset of antiallodynic action compared to DMI, we used genetically modified mice to gain insight into RGS protein-associated pathways that modulate the efficacy of TIAN relative to DMI in models of neuropathic pain. Because we observed similar behavioral responses to both TIAN and DMI treatment in RGS4, RGSz1, and RGS9 knockout mice, we performed RNA sequencing on the NAc of TIAN- and DMI-treated mice after prolonged SNI to further clarify potential mechanisms underlying TIANs faster therapeutic actions. Our bioinformatic analysis revealed distinct transcriptomic signatures between the two drugs, with TIAN more directly reversing SNI-induced differentially expressed genes, and further predicted several upstream regulators that may be implicated in onset of action. This new understanding of the molecular pathways underlying TIAN action may enable the development of novel and more efficacious pharmacological approaches for the management of neuropathic pain.
(© 2023. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)
Databáze: MEDLINE
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