{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:31:30Z","timestamp":1782779490458,"version":"3.54.5"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2010,12,1]],"date-time":"2010-12-01T00:00:00Z","timestamp":1291161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neuropathic pain produced by damage to or dysfunction of the nervous system is a common and severely disabling state that affects millions of people worldwide. Recent evidence indicates that activated microglia are key cellular intermediaries in the pathogenesis of neuropathic pain and that ATP serves as the mediator. However, the <jats:italic>in vivo<\/jats:italic> mechanism underlying the retention of activated microglia in the injured region has not yet been completely elucidated. Prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>) is the principal proinflammatory prostanoid and plays versatile roles by acting via four PGE receptor subtypes, EP1\u2010EP4. In the present study, we investigated the role of PGE<jats:sub>2<\/jats:sub> in spinal microglial activation in relation to neuropathic pain by using genetic and pharmacological methods. Mice deficient in microsomal prostaglandin E synthase\u20101 impaired the activation of microglia and the NMDA\u2010nitric oxide (NO) cascade in spinal neurons in the dorsal horn and did not exhibit mechanical allodynia after peripheral nerve injury. The intrathecal injection of indomethacin, a nonsteroidal anti\u2010inflammatory drug, ONO\u20108713, a selective EP1 antagonist, or 7\u2010nitroindole, a neuronal NO synthase inhibitor, attenuated mechanical allodynia and the increase in activated microglia observed in the established neuropathic\u2010pain state. We further demonstrated that ATP\u2010induced microglial migration was blocked <jats:italic>in vitro<\/jats:italic> by PGE<jats:sub>2<\/jats:sub> via EP2 and by <jats:italic>S<\/jats:italic>\u2010nitrosoglutathione, an NO donor. Taken together, the present study suggests that PGE<jats:sub>2<\/jats:sub> participated in the maintenance of neuropathic pain <jats:italic>in vivo<\/jats:italic> not only by activating spinal neurons, but also by retaining microglia in the central terminals of primary afferent fibers via EP2 subtype and via EP1\u2010mediated NO production. \u00a92010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.21090","type":"journal-article","created":{"date-parts":[[2010,12,1]],"date-time":"2010-12-01T22:41:23Z","timestamp":1291243283000},"page":"208-218","source":"Crossref","is-referenced-by-count":58,"title":["A novel role of prostaglandin E<sub>2<\/sub> in neuropathic pain"],"prefix":"10.1002","volume":"59","author":[{"given":"Shunji","family":"Kunori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Matsumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiko","family":"Okuda\u2010Ashitaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayo","family":"Katano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent 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