Secreted PLA2-III is a possible therapeutic target to treat neuropathic pain.
Biochem Biophys Res Commun
; 568: 167-173, 2021 09 03.
Article
em En
| MEDLINE
| ID: mdl-34237486
ABSTRACT
Lysophosphatidic acid (LPA) plays a critical role in developing and maintaining chronic pain in various animal models. Previous studies have reported that cytosolic and calcium-independent phospholipase A2 (PLA2) is involved in the LPA receptor-mediated amplification of LPA production in the spinal dorsal horn (SDH) after nerve injury, while the involvement of secreted PLA2 (sPLA2) remains unclear. The present study revealed that only sPLA2 -III among 11 species of PLA2 showed a significant upregulation of gene expression in the SDH. Intraspinal injection of adeno-associated virus-miRNA targeting sPLA2-III prevented hyperalgesia and unique hypoalgesia in mice treated with partial sciatic nerve ligation. In addition, intrathecal treatment with antisense oligodeoxynucleotide or siRNA targeting sPLA2-III significantly reversed the established thermal hyperalgesia. In the high-throughput screening of sPLA2-III inhibitors from the chemical library, we identified two hit compounds. Through in vitro characterization of PLA2 inhibitor profiles and in vivo assessment of the anti-hyperalgesic effects of known PLA2 inhibitors as well as hit compounds, sPLA2-III was found to be a novel therapeutic target molecule for the treatment of Neuropathic pain.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfolipases A2 do Grupo III
/
Neuralgia
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2021
Tipo de documento:
Article