{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:51:17Z","timestamp":1791348677076,"version":"4.3.1"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370986"],"award-info":[{"award-number":["82370986"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"abstract":"ABSTRACT<\/jats:title>\n \n Aim<\/jats:title>\n Nocturnal exacerbation of pulpitis\u2010induced pain severely disrupts patients' sleep and quality of life, increasing emergency dental care burden. However, the exact mechanisms underlying nocturnal pain remain poorly understood, limiting the development of targeted analgesic strategies. Here, we explored the circadian characteristics of pulpitis\u2010induced pain in mice and the role of clock genes in its nocturnal exacerbation.<\/jats:p>\n <\/jats:sec>\n \n Methodology<\/jats:title>\n An experimental pulpitis model was established via pulp exposure, with stability confirmed by Micro\u2010computed tomography and haematoxylin and eosin staining. Von Frey test was used to investigate the circadian characteristics of pulpitis\u2010induced pain. Immunofluorescence (IF) staining, in\u00a0vivo fibre photometry, and stereotaxic injection were combined to evaluate the circadian variation of neuronal activity in the anterior cingulate cortex (ACC), as well as its role in modulating the circadian rhythm of pulpitis\u2010induced pain. Single\u2010nuclei RNA sequencing (snRNA\u2010seq) was performed to screen differentially expressed genes. Quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR), Western blot, and IF staining were used to detect the expression changes and neuronal expression profile of brain and muscle ARNT\u2010like protein 1 (BMAL1). Adeno\u2010associated virus selectively overexpressed BMAL1 in pyramidal neurons was constructed. Combined with behavioural tests, Western blot, and in\u00a0vivo fibre photometry, the role and underlying mechanism of BMAL1 in the nocturnal exacerbation of pulpitis\u2010induced pain were evaluated.<\/jats:p>\n <\/jats:sec>\n \n Result<\/jats:title>\n \n On Day 3 after pulp exposure, the pain threshold exhibited a distinct circadian rhythm, reaching its minimum during the light phase. Excitotoxic lesion and fibre photometry experiments further indicated that neurons in the ACC are critical for regulating the circadian rhythm of pulpitis\u2010induced pain. Using snRNA\u2010seq, qRT\u2010PCR, Western blot, and IF staining, we screened and validated a significant reduction in BMAL1 expression in the ACC of mice with pulpitis during the light phase, particularly in pyramidal neurons. Furthermore, overexpression of BMAL1 in ACC pyramidal neurons alleviated the nocturnal exacerbation of pulpitis\u2010induced pain, alongside decreased activation of the Ca\n 2+<\/jats:sup>\n \/calmodulin\u2010dependent protein kinase II (CaMKII) signaling pathway and reduced pyramidal neuronal excitability.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Our findings elucidate the core role of BMAL1 in contributing to nocturnal pain exacerbation of pulpitis and offer a valuable therapeutic target for the management of nocturnal pain in patients with pulpitis.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/iej.70283","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:27:48Z","timestamp":1791347268000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BMAL1<\/scp>\n in Anterior Cingulate Cortex Pyramidal Neurons Relieves Pulpitis\u2010Induced Nocturnal Pain"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4297-9949","authenticated-orcid":false,"given":"Yuting","family":"Bai","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Centre for Oral Diseases, Shaanxi Clinical Research Centre for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology The Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Si","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Centre for Oral Diseases, Shaanxi Clinical Research Centre for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology The Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Centre for Oral Diseases, Shaanxi Clinical Research Centre for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology The Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Centre for Oral Diseases, Shaanxi Clinical Research Centre for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology The Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Nian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Centre for Oral Diseases, Shaanxi Clinical Research Centre for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology The Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yundi","family":"Qiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Centre for Oral Diseases, Shaanxi Clinical Research Centre for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology The Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoke","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Centre for Oral Diseases, Shaanxi Clinical Research Centre for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology The Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0697-4968","authenticated-orcid":false,"given":"Jing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences The Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8909-328X","authenticated-orcid":false,"given":"Li\u2010an","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Centre for Oral Diseases, Shaanxi Clinical Research Centre for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology The Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"issue":"43","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adj1010","article-title":"Synaptic BMAL1 Phosphorylation Controls Circadian Hippocampal Plasticity","volume":"9","author":"Barone I.","year":"2023","journal-title":"Science Advances"},{"issue":"10482","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/S0140-6736(24)02811-3","article-title":"Trends in the Global, Regional, and National Burden of Oral Conditions From 1990 to 2021: A Systematic Analysis for the Global Burden of Disease Study 2021","volume":"405","author":"Bernabe E.","year":"2025","journal-title":"Lancet"},{"issue":"8","key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/nrn.2016.68","article-title":"Synaptic Plasticity in the Anterior Cingulate Cortex in Acute and Chronic 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V. P.","year":"2016","journal-title":"Nature Reviews. Neuroscience"},{"issue":"1","key":"e_1_2_12_5_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-026-73772-z","article-title":"Nociceptor Circadian Clock Genes Control Excitability and Pain Perception in Mice in a Sex\u2010 and Time\u2010Dependent Manner","volume":"17","author":"Br\u00e9cier A.","year":"2026","journal-title":"Nature Communications"},{"issue":"7","key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/S0092-8674(00)00205-1","article-title":"Mop3 Is an Essential Component of the Master Circadian Pacemaker in Mammals","volume":"103","author":"Bunger M. K.","year":"2000","journal-title":"Cell"},{"issue":"25","key":"e_1_2_12_7_1","article-title":"Locus Coeruleus Noradrenergic\u2010Spinal Projections Contribute to Electroacupuncture\u2010Mediated Antinociception in Postoperative Pain in Mice","volume":"12","author":"Chu W. 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