I am a
Home I AM A Search Login

Papers of the Week

Papers: 3 Jul 2021 - 9 Jul 2021

Animal Studies

2021 Jul 05

Biochem Biophys Res Commun


Secreted PLA-III is a possible therapeutic target to treat neuropathic pain.


Tanaka K, Dozono N, Neyama H, Nagai J, Tsukahara R, Nagayasu K, Kaneko S, Ueda H
Biochem Biophys Res Commun. 2021 Jul 05; 568:167-173.
PMID: 34237486.


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 A (PLA) 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 PLA (sPLA) remains unclear. The present study revealed that only sPLA -III among 11 species of PLA showed a significant upregulation of gene expression in the SDH. Intraspinal injection of adeno-associated virus-miRNA targeting sPLA-III prevented hyperalgesia and unique hypoalgesia in mice treated with partial sciatic nerve ligation. In addition, intrathecal treatment with antisense oligodeoxynucleotide or siRNA targeting sPLA-III significantly reversed the established thermal hyperalgesia. In the high-throughput screening of sPLA-III inhibitors from the chemical library, we identified two hit compounds. Through in vitro characterization of PLA inhibitor profiles and in vivo assessment of the anti-hyperalgesic effects of known PLA inhibitors as well as hit compounds, sPLA-III was found to be a novel therapeutic target molecule for the treatment of Neuropathic pain.