The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms Implicated

Neuropathic pain is a type of pain that persists for a long time and becomes pathological. Additionally, the anxiodepressive disorders derived from neuropathic pain are difficult to palliate with the current treatments and need to be resolved. Then, using male mice with neuropathic pain provoked by...

Descripción completa

Detalles Bibliográficos
Autores: Suárez-Rojas, I, Pérez-Fernández, M, Bai, X, Martínez-Martel, I, Intagliata, S, Pittalà, V, Salerno, L, Pol, O
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p17318
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17318
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85175325091&doi=10.3390%2fantiox12101859&partnerID=40&md5=7a4c39f229d50c1ad27cdade2b4c6e1e
Access Level:acceso abierto
Palabra clave:analgesia
anxiety
depression
dimethyl fumarate
heme oxygenase 1
inflammasome
neuropathic pain
Nrf2 transcription factor
oxidative stress
Descripción
Sumario:Neuropathic pain is a type of pain that persists for a long time and becomes pathological. Additionally, the anxiodepressive disorders derived from neuropathic pain are difficult to palliate with the current treatments and need to be resolved. Then, using male mice with neuropathic pain provoked by chronic constriction of the sciatic nerve (CCI), we analyzed and compared the analgesic actions produced by three new heme oxygenase 1 (HO-1) inducers, 1m, 1b, and 1a, with those performed by dimethyl fumarate (DMF). Their impact on the anxiety- and depressive-like comportments and the expression of the inflammasome NLRP3, Nrf2, and some antioxidant enzymes in the dorsal root ganglia (DRG) and amygdala (AMG) were also investigated. Results revealed that the administration of 1m, 1b, and DMF given orally for four days inhibited the allodynia and hyperalgesia caused by CCI, while 1a merely reduced the mechanical allodynia. However, in the first two days of treatment, the antiallodynic effects produced by 1m were higher than those of 1a and DMF, and its antihyperalgesic actions were greater than those produced by 1b, 1a, and DMF, revealing that 1m was the most effective compound. At four days of treatment, all drugs exerted anxiolytic and antidepressant effects, decreased the NLRP3 levels, and increased/normalized the Nrf2, HO-1, and superoxide dismutase 1 levels in DRG and AMG. Data indicated that the dual modulation of the antioxidant and inflammatory pathways produced by these compounds, especially 1m, is a new promising therapeutic approach for neuropathic pain and related emotional illnesses.