Lysophosphatidic acid (LPA) involvement in central post-stroke pain (CPSP)

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We firstly found that lysophosphatidic acid receptor 1 (LPA1) signaling initiates nerve injury-induced neuropathic pain (NP) in mice (Nature Medicine, 2004) and LPA1 and LPA3 signaling are also involved in the development and maintenance of various mouse models of chronic pain, such as peripheral neuropathic paclitaxel-induced pain (Mol Pain, 2014) and central emotional fibromyalgia (Neurobiol of Pain, 2017). Here we studied to see whether LPA1 and LPA3 signaling are also involved in the central NP, central post-stroke pain (CPSP), which is one of the most intractable chronic pain syndromes in cerebral ischemia, though useful treatment has not been established. The CPSP model in our study was developed by the late stage of tPA treatment 6 h after photochemically induced thrombosis (PIT) of left middle cerebral artery (MCA). Significant abnormal pain behaviors in the thermal and mechanical test were found on both sides for more than 2 weeks, and they were abolished in Lpar1 and Lpar3 KO. In addition, the repeated treatments with Ki-16425, an LPA1/3 receptor antagonist also abolished the abnormal pain behaviors. When LPA levels were measured by LC-MS/MS, tPA-dependent increase in LPA levels were found in some brain regions. We will discuss why tPA-accelerated bilateral CPSP occurs in the PIT stroke model on the left side.