Treatment with slow-releasing hydrogen sulfide donors inhibits the nociceptive and depressive-like behaviours accompanying chronic neuropathic pain : Endogenous antioxidant system activation
Cabarga, Laura (Universitat Autònoma de Barcelona. Institut de Neurociències)
Batallé Melgarejo, Gerard (Institut de Recerca Sant Pau)
Pol, Olga (Institut de Recerca Sant Pau)

Date:	2020
Abstract:	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.
Grants:	Instituto de Salud Carlos III PI1800645
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Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Analgesia ; Antioxidants ; Anxiety ; Depression ; Hydrogen sulfide ; Neuropathic pain
Published in:	Journal of Psychopharmacology, Vol. 34, Num. 7 (January 2020) , p. 737-749, ISSN 1461-7285

DOI: 10.1177/0269881120913154

Postprint 13 p, 6.8 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
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