Rosuvastatin Synergistically Enhances the Antinociceptive Efficacy of Duloxetine in Paclitaxel-Induced Neuropathic Pain in Mice

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dc.contributor.authorLobos, Nicolás
dc.contributor.authorLux, Sebastián
dc.contributor.authorZepeda, Ramiro Javier
dc.contributor.authorPelissier, Teresa
dc.contributor.authorMarcos, José Luis
dc.contributor.authorBustos-Quevedo, Gonzalo
dc.contributor.authorHernández, Alejandro
dc.contributor.authorConstandil, Luis
dc.date.accessioned2023-07-14T15:43:06Z
dc.date.available2023-07-14T15:43:06Z
dc.date.issued2023-05-06
dc.description.abstractPaclitaxel, a widely used cancer chemotherapeutic agent, has high incidence of neurotoxicity associated with the production of neuropathic pain, for which only duloxetine has shown significant but moderate analgesic effect. Since statins, classically used to reduce hypercholesterolemia, have shown antinociceptive effect in preclinical studies on neuropathic pain, we studied whether the antinociceptive efficacy of duloxetine could be synergistically potentiated by rosuvastatin in a model of paclitaxel-induced neuropathy in mice. The astrocytic and microglial responses in the spinal cord of paclitaxel-treated mice were also assessed by measuring GFAP and CD11b proteins, respectively. Paclitaxel treatment did not impair motor coordination and balance in rotarod testing. Rosuvastatin, duloxetine, and the rosuvastatin/duloxetine combination (combined at equieffective doses) dose-dependently decreased mechanical allodynia (ED30, von Frey testing) and thermal hyperalgesia (ED50, hot plate testing) in paclitaxel-treated mice. Isobolographic analysis showed a superadditive interaction for rosuvastatin and duloxetine, as both the ED30 and ED50 for the rosuvastatin/duloxetine combination contained only a quarter of each drug compared to the individual drugs. The rosuvastatin/duloxetine combination reversed paclitaxel-induced GFAP overexpression, indicating that such effects might depend in part on astrocyte inactivation. Results suggest that statins could be useful in synergistically enhancing the efficacy of duloxetine in some chemotherapy-induced neuropathic conditions.es_ES
dc.identifier.issn1422-0067
dc.identifier.other10.3390/ijms24098359
dc.identifier.urihttps://hdl.handle.net/20.500.12536/1946
dc.language.isoenes_ES
dc.sourceInternational Journal of Molecular Scienceses_ES
dc.subjectRosuvastatines_ES
dc.subjectDuloxetinees_ES
dc.subjectPaclitaxeles_ES
dc.subjectChronic paines_ES
dc.subjectChemotherapy-induced neuropathyes_ES
dc.subjectIsobolographic studyes_ES
dc.titleRosuvastatin Synergistically Enhances the Antinociceptive Efficacy of Duloxetine in Paclitaxel-Induced Neuropathic Pain in Micees_ES
dc.typeArtículo de revistaes_ES
uvm.escuelaEscuela de Ciencias Agrícolas y Veterinariases_ES
uvm.indexScopuses_ES
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