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Symposia

日本学術振興会先端研究拠点事業共催:痛み研究最前線
JSPS Core-to-Core Program:The front line of pain research

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開催日
2010年09月04日(土)
時 間
08:30 - 11:00
会 場
Room 1
Chairperson(s)
柿木 隆介 / Ryusuke Kakigi (自然科学研究機構 生理学研究所 統合生理研究系 / Department of Integrative Physiology, National Institute for Physiological Sciences)
水村 和枝 / Kazue Mizumura (名古屋大学環境医学研究所 神経系分野II / Dept. Neurosci. II, Res. Inst. Environ. Med., Nagoya Univ., Nagoya 464-8601, Japan)

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リゾホスファチジン酸を介した末梢性および中枢性の慢性痛のフィードフォワード性増幅機構
Feed-forward system of peripheral and central chronic pain through lysophosphatidic acid

演題番号 : S3-1-1-2

植田 弘師 / Hiroshi Ueda:1 永井 潤 / Jun Nagai:1 

1:長崎大学大学院医歯薬学総合研究科 / Nagasaki University Graduate School of Biomedical Sience 

 

We have identified lysophosphatidic acid (LPA) as an initiator of peripheral neuropathic pain induced by partial sciatic nerve injury (Inoue et al., Nature Med 2004). Using LPA receptor1 gene KO mice, we have successfully characterized the molecular mechanisms underlying neuropathic pain following partial injury of sciatic nerve (pISN), including altered DRG gene expression (e.g. Ca channel), A-fiber demyelination and spinal PKCgamma expression (Ueda, Pharmacol & Ther, 2006; Mol Pain, 2008 Reviews). The study based on LPA-mediated demyelination mechanisms successfully proposed E64d, a calpain inhibitor to cure the peripheral neuropathic pain (Xie et al., J Neurochem, 2010). Our recent concerns are on the further mechanisms of sustained pain for long days in animals or long years in clinic. They are related to the feed-forward system through amplifying pain mechanisms due to an LPA-induced activation of neuron-glia or possibly related cytokine networks, and through an activation of brain sensory and emotional pain pathways. Key findings in this feed-forward system are the discoveries of involvement of LPA-induced de novo LPA production and microglia activation. In the de novo LPA synthesis, LPA receptor3 and autotaxin (lysophospholipase D) were found to play key roles (Ma et al., JPET, 2010). Regarding the LPA-induced microglia activation, it was found to play a role in the development stage rather than the maintenance. Regarding brain mechanisms, on the other hand, we found that the LPA receptor1-mediated activation of thalamus following pISN may cause the emotional system-related pain as well as sensory system-oriented pain. We also found that microglial activation is involved in this type of peripheral nerve injury-induced central pain.

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