{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:21:24Z","timestamp":1787574084221,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T00:00:00Z","timestamp":1570752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T00:00:00Z","timestamp":1570752000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neuropathic pain correlates with a lesion or other dysfunction in the nervous system. Sphingosine\u20101\u2010phosphate receptor 2 (S1P2) is expressed in the central nervous system and modulates synaptic plasticity. The present study aimed to investigate the role of S1P2 in neuropathic pain caused by chronic constriction injury (CCI). Sprague\u2010Dawley rats were allocated into eight groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915 for each group): sham, CCI, CCI\u2009+\u2009green fluorescent protein, CCI\u2009+\u2009S1P2, CCI\u2009+\u2009Ctrl\u2010short hairpin RNA (shRNA), CCI\u2009+\u2009S1P2 shRNA, CCI\u2009+\u2009S1P2\u2009+\u2009CYM\u20105442, and CCI\u2009+\u2009S1P2 shRNA\u2009+\u2009CYM\u20105442. The CCI model was established via sciatic nerve ligation. S1P2 was overexpressed or knocked down by intrathecal injection of adeno\u2010associated virus\u2010S1P2 (AAV\u2010S1P2) or AAV\u2010S1P2 shRNA. The S1P1 agonist, CYM\u20105442 (1\u2009mg\/kg), was injected intraperitoneally after surgery. S1P2 expression, pain thresholds, apoptosis signaling, inflammation, and oxidative stress in rats were then examined. We found that sciatic nerve injury downregulated S1P2 expression in the spinal cords of rats. S1P2 overexpression enhanced pain thresholds. In contrast, S1P2 knockdown decreased pain thresholds in rats exposed to CCI. CCI and S1P2 silencing increased secretion of interleukin\u20101\u03b2 (IL\u20101\u03b2), IL\u20106, and CCL2, whereas S1P2 overexpression decreased. S1P2 impeded CCI\u2010induced reactive oxygen species (ROS) production and runt\u2010related transcription factors 3 (RUNX3) downregulation, and S1P2 knockdown had the opposite effect. S1P2 overexpression suppressed Bax and active caspase 3 expression and promoted Bcl\u20102 expression, whereas loss of S1P2 reversed their expression. Additionally, S1P1 activation counteracted the effect of S1P2 on pain sensitivity. In conclusion, S1P2 is downregulated in CCI rats and may help modulate neuropathic pain via the ROS\/RUNX3 pathway.\n                  <\/jats:p>","DOI":"10.1002\/jcp.29280","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T05:45:36Z","timestamp":1570772736000},"page":"3864-3873","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Sphingosine\u20101\u2010phosphate receptor 2 modulates pain sensitivity by suppressing the ROS\u2010RUNX3 pathway in a rat model of neuropathy"],"prefix":"10.1002","volume":"235","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4382-3002","authenticated-orcid":false,"given":"Yinyu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Zhoukou Central Hospital  Zhoukou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of 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