Lysophosphatidic acid LPA1 and LPA3 receptors play roles in the maintenance of late tissue plasminogen activator-induced central poststroke pain in mice

機関リポジトリ HANDLE

抄録

We developed a mouse model for central post-stroke pain (CPSP), a centrally-originated neuropathic pain (NeuP). In this mode, mice were first injected with Rose Bengal, followed by photo-irradiation of left middlecerebral artery (MCA) to generate thrombosis. Although the MCA thrombosis was soon dissolved, the reducedblood flow remained for more than 24 h due to subsequent occlusion of microvessels. This photochemicallyinduced thrombosis (PIT) model showed a hypersensitivity to the electrical stimulation of both sides of paw, butdid not show any abnormal pain in popular thermal or mechanical nociception tests. When tissue-type plas-minogen activator (tPA) was injected 6h after the PIT stress, tPA-dependent hypersensitivity to the electricalpaw stimulation and stable thermal and mechanical hyperalgesia on both sides for more than 17 or 18 days afterthe PIT treatment. These hyperalgesic effects were abolished in lysophosphatidic acid receptor 1 (LPA1)- andlysophosphatidic acid receptor 3 (LPA3)-deficient mice. When Ki-16425, an LPA1and LPA3antagonist wastreated twice daily for 6days consecutively, the thermal and mechanical hyperalgesia at day 17 and 18 weresignificantly reversed. The liquid chromatography?mass spectrometry (LC?MS/MS) analysis revealed that thereis a significant increase in several species of LPA molecules in somatosensory S-I and medial dorsal thalamus (MD), but not in striatum or ventroposterior thalamus. All these results suggest that LPA1and LPA3signalingplay key roles in the development and maintenance of CPSP.

Neurobiology of Pain, 5, art.no.100020; 2019

収録刊行物

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ