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Microglia represent a major cell type expressing P2X7Rs. The activation of microglial P2X7Rs causes the release of pro-inflammatory cytokines such as interleukin-1\u03b2 (IL-1\u03b2). This response has been implicated in neuroinflammatory states in the central nervous system and in various diseases, including neuropathic pain. Thus, P2X7R may represent a potential therapeutic target. In the present study, we screened a chemical library of clinically approved drugs (1979 compounds) by high-throughput screening and showed that the Ca2+ channel blocker cilnidipine has an inhibitory effect on rodent and human P2X7R. In primary cultured rat microglial cells, cilnidipine inhibited P2X7R-mediated Ca2+ responses and IL-1\u03b2 release. Moreover, in a rat model of neuropathic pain, the intrathecal administration of cilnidipine produced a reversal of nerve injury-induced mechanical hypersensitivity, a cardinal symptom of neuropathic pain. These results point to a new inhibitory effect of cilnidipine on microglial P2X7R-mediated inflammatory responses and neuropathic pain, proposing its therapeutic potential.<\/jats:p>","DOI":"10.3390\/cells10020434","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T20:56:21Z","timestamp":1613681781000},"page":"434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["New Inhibitory Effects of Cilnidipine on Microglial P2X7 Receptors and IL-1\u03b2 Release: An Involvement in its Alleviating Effect on Neuropathic Pain"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0596-1671","authenticated-orcid":false,"given":"Tomohiro","family":"Yamashita","sequence":"first","affiliation":[{"name":"Department of Global Healthcare, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"},{"name":"Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawako","family":"Kamikaseda","sequence":"additional","affiliation":[{"name":"Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Tozaki-Saitoh","sequence":"additional","affiliation":[{"name":"Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"},{"name":"Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose M. M.","family":"Caaveiro","sequence":"additional","affiliation":[{"name":"Department of Global Healthcare, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhide","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"},{"name":"Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1152\/physrev.00045.2019","article-title":"Neuropathic Pain: From Mechanisms to Treatment","volume":"101","author":"Finnerup","year":"2021","journal-title":"Physiol. 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