Secreted PLA2-III is a possible therapeutic target to treat neuropathic pain.
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| 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.
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| Authors | Keigo Tanaka, Naoki Dozono, Hiroyuki Neyama, Jun Nagai, Ryoko Tsukahara, Kazuki Nagayasu, Shuji Kaneko, Hiroshi Ueda |
| Journal | Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 568 Pg. 167-173 (09 03 2021) ISSN: 1090-2104 [Electronic] United States |
| PMID | 34237486 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2021 Elsevier Inc. All rights reserved. |
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