{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:33:02Z","timestamp":1777944782964,"version":"3.51.4"},"reference-count":50,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H06276 (Advanced Animal Model Support: AdAMS)"],"award-info":[{"award-number":["16H06276 (Advanced Animal Model Support: AdAMS)"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K08859"],"award-info":[{"award-number":["18K08859"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K08925"],"award-info":[{"award-number":["21K08925"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K09037"],"award-info":[{"award-number":["22K09037"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K12094"],"award-info":[{"award-number":["24K12094"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019890","name":"university of miyazaki hospital","doi-asserted-by":"publisher","award":["Grant-in-Aid for Clinical Research"],"award-info":[{"award-number":["Grant-in-Aid for Clinical Research"]}],"id":[{"id":"10.13039\/100019890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Calcineurin inhibitors, including tacrolimus (FK506), are used as immunosuppressive agents and can cause unexplained calcineurin inhibitor-induced pain syndrome (CIPS). We investigated how FK506 affects the expression of\n                    <jats:italic toggle=\"yes\">\n                      Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7\n                    <\/jats:italic>\n                    , a voltage-gated Na\n                    <jats:sup>+<\/jats:sup>\n                    channel implicated in pain perception that is upregulated in dorsal root ganglion (DRG) neurons in several pain disorders. We generated a model of FK506-induced pain by administering FK506 to Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7\u2013ChR2 mice, which exhibit light-responsive pain. To evaluate nociceptive responses, paw withdrawal threshold (PWT) was measured using the von Frey test. The optogenetic place aversion (OPA) and light irradiation paw withdrawal tests were also performed. On the 11th day of initial injection, DRGs were dissected from mice under anesthesia and analyzed for\n                    <jats:italic toggle=\"yes\">\n                      Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7\n                    <\/jats:italic>\n                    expression using quantitative reverse transcription PCR (RT-qPCR). PWT was also measured for mice that received the selective Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 inhibitor or vehicle. PWT was lower in FK506-treated mice than in those administered the vehicle on the 8th and 12th days after initial FK506 injection (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.05). Mechanical hypersensitivity was reversible and peaked at around 10 days after FK506 administration. OPA and light irradiation paw withdrawal test results corroborated the hypersensitivity to light-responsivity.\n                    <jats:italic toggle=\"yes\">\n                      Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7\n                    <\/jats:italic>\n                    mRNA levels in DRG were higher in FK506-treated mice than in those administered the vehicle on the 11th day (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.05). A selective Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 inhibitor reversed FK506-induced pain. Increased\n                    <jats:italic toggle=\"yes\">\n                      Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7\n                    <\/jats:italic>\n                    expression in DRG neurons may be responsible for FK506-induced peripheral neuropathy. Our findings suggest that endogenous calcineurin regulates\n                    <jats:italic toggle=\"yes\">\n                      Na\n                      <jats:sub>V<\/jats:sub>\n                      1.7\n                    <\/jats:italic>\n                    expression. Thus, selective Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 inhibition could be a potential therapeutic strategy for CIPS.\n                  <\/jats:p>","DOI":"10.1177\/17448069251414260","type":"journal-article","created":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T11:28:44Z","timestamp":1767439724000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["FK506 causes pain by upregulating Na\n                    <sub>V<\/sub>\n                    1.7 channels in the spinal dorsal root ganglia of Na\n                    <sub>V<\/sub>\n                    1.7\u2013ChR2 mice"],"prefix":"10.1177","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2660-2179","authenticated-orcid":false,"given":"Toyoaki","family":"Maruta","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan"},{"name":"Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiji","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Division of Community Medicine for Anesthesiology, Hiroshima University, Hiroshima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Kouroki","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mio","family":"Kurogi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3776-8115","authenticated-orcid":false,"given":"Naoyuki","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,1,3]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.212563"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/AJP.0b013e31823a67f1"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1797.2006.00708.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndtplus\/sfr156"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2011.120"},{"key":"e_1_3_3_7_2","article-title":"Calcineurin as a nociceptor modulator","volume":"12","author":"Smith HS","year":"2009","unstructured":"Smith HS. Calcineurin as a nociceptor modulator. 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