{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T22:58:45Z","timestamp":1794265125646,"version":"4.9.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771095"],"award-info":[{"award-number":["81771095"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071235"],"award-info":[{"award-number":["82071235"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Dental pulpitis often induces severe pain, and the molecular immune response is remarkable in both peripheral and central nervous system. Accumulating evidence indicates that activated microglia in the medullary dorsal horn (MDH) contribute to dental pulpitis induced pain. The P2X7 receptor plays an important role in driving pain and inflammatory processes, and its downstream target hypoxia-induced factor-1\u03b1 (HIF-1\u03b1) has a crucial role in maintaining inflammation. However, the relationship between P2X7 and HIF-1\u03b1 in dental inflammatory pain remains unclear. This study demonstrated that the degree of inflammation in the dental pulp tissue became more severe in a time-dependent manner by establishing a rat dental pulpitis model<jats:italic>via<\/jats:italic>pulp exposure. Meanwhile, the expression of P2X7, HIF-1\u03b1, IL-1\u03b2, and IL-18 in the MDH increased most on the seventh day when the pain threshold was the lowest in the dental pulpitis model. Furthermore, lipopolysaccharides (LPS) increased P2X7-mediated HIF-1\u03b1 expression in microglia. Notably, the suppression of P2X7 caused less IL-1\u03b2 and IL-18 release and lower HIF-1\u03b1 expression, and P2X7 antagonist Brilliant Blue G (BBG) could alleviate pain behaviors of the dental pulpitis rats. In conclusion, our results provide further evidence that P2X7 is a key molecule, which regulates HIF-1\u03b1 expression and inflammation in dental pulpitis-induced pain.<\/jats:p>","DOI":"10.3389\/fnmol.2022.1015751","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T13:11:46Z","timestamp":1666789906000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Ligand-gated ion channel P2X7 regulates hypoxia-induced factor-1\u03b1 mediated pain induced by dental pulpitis in the medullary dorsal horn"],"prefix":"10.3389","volume":"15","author":[{"given":"Jing","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shukai","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-an","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.physbeh.2018.06.021","article-title":"Lipopolysaccharide-mediated inflammatory priming potentiates painful post-traumatic trigeminal neuropathy","volume":"194","author":"Boucher","year":"2018","journal-title":"Physiol. 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