Peroxisome proliferator-activated receptor gamma agonist pioglitazone alleviates hemorrhage-induced thalamic pain and neuroinflammation.
Int Immunopharmacol
; 124(Pt B): 110991, 2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-37774485
ABSTRACT
BACKGROUND:
Thalamic pain frequently occurs after stroke and is a challenging clinical issue. However, the mechanisms underlying thalamic pain remain unclear. Neuroinflammation is a key determining factor in the occurrence and maintenance of hemorrhage-induced thalamic pain. Pioglitazone is an agonist of peroxisome proliferator-activated receptor gamma (PPARγ) and shows anti-inflammatory effects in multiple diseases. The present work focused on exploring whether PPARγ is related to hemorrhage-induced thalamic pain.METHODS:
Immunostaining was conducted to analyze the cellular localization of PPARγ and co-localization was evaluated with NeuN, ionized calcium-binding adapter molecular 1 (IBA1), and glia fibrillary acidic protein (GFAP). Western blot analyses were used to evaluate MyD88, pNF-κB/NF-κB, pSTAT6/STAT6, IL-1ß, TNF-α, iNOS, Arg-1, IL-4, IL-6, and IL-10 expression. Behavioral tests in mice were conducted to evaluate continuous pain hypersensitivity.RESULTS:
We found that pioglitazone appeared to mitigate the contralateral hemorrhage-induced thalamic pain while inhibiting inflammatory responses. Additionally, Pioglitazone induced phosphorylation of STAT6 and suppressed the phosphorylation NF-κB in our model of thalamic pain. These effects could be partially reversed with the PPARγ antagonist GW9662.CONCLUSION:
The PPARγ agonist pioglitazone can mitigate mechanical allodynia by suppressing the NF-κB inflammasome while activating the STAT6 signal pathway, which are well-known to be associated with inflammation.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tiazolidinedionas
/
PPAR gama
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article