Treatment with slow-releasing hydrogen sulfide donors inhibits the nociceptive and depressive-like behaviours accompanying chronic neuropathic pain

Background: Therapies to treat chronic neuropathic pain and its associated comorbidities are limited. Recent studies demonstrated that the administration of slow-releasing hydrogen sulfide (HS) donors inhibited chemotherapy-induced neuropathic pain. However, the antidepressant or anxiolytic effects...

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Detalles Bibliográficos
Autores: Cabarga, Laura, Batallé Melgarejo, Gerard|||0000-0003-2065-2914, Pol, Olga|||0000-0002-4621-8457
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:327009
Acceso en línea:https://ddd.uab.cat/record/327009
https://dx.doi.org/urn:doi:10.1177/0269881120913154
Access Level:acceso abierto
Palabra clave:Analgesia
Antioxidants
Anxiety
Depression
Hydrogen sulfide
Neuropathic pain
Descripción
Sumario:Background: Therapies to treat chronic neuropathic pain and its associated comorbidities are limited. Recent studies demonstrated that the administration of slow-releasing hydrogen sulfide (HS) donors inhibited chemotherapy-induced neuropathic pain. However, the antidepressant or anxiolytic effects of these compounds and their mechanisms of action during chronic neuropathic pain have not been evaluated. Aims: To determine whether the administration of two slow-releasing HS donors, allyl isothiocyanate (A-ITC) and phenyl isothiocyanate (P-ITC), inhibits the nociceptive and emotional disorders associated with chronic neuropathic pain. Methods: In C57BL/6 male mice with neuropathic pain caused by the chronic constriction of the sciatic nerve, we assessed the effects of intraperitoneal administration of A-ITC and P-ITC in (a) the mechanical allodynia, thermal hyperalgesia and thermal allodynia induced by nerve ligation; (b) the anxiety- and depressive-like behaviours linked with neuropathic pain; (c) glial activation and mitogen-activated protein kinases phosphorylation, and (d) expression of the antioxidant enzymes, heme oxygenase 1 (HO-1), NADPH quinone oxidoreductase1, and glutathione S-transferase mu-1 (GSTM1), and alpha-1 (GSTA1), in hippocampus and prefrontal cortex (PFC). Results: Both treatments inhibited the allodynia and hyperalgesia, depressive-like behaviours, astroglial activation, and the extracellular signal-regulated kinase 1/2 phosphorylation but were unable to abolish the anxiety-like behaviours accompanying neuropathic pain. A-ITC and P-ITC also augmented the expression of HO-1, GSTM1, and GSTA1 in the hippocampus and/or PFC. Conclusions: The administration of slow-releasing HS donors might be a promising treatment for the management of chronic neuropathic pain and some associated comorbidities via inhibiting the inflammatory and plasticity changes, and activating the endogenous antioxidant responses.