International endodontic journal · 2026
BMAL1 in Anterior Cingulate Cortex Pyramidal Neurons Relieves Pulpitis-Induced Nocturnal Pain.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Bai Yuting, Si Jialin, Zhang Jing, Yu Zhuo, Nian Meng, Qiao Yundi, Wu Xiaoke, Huang Jing, Wu Li-An
Аннотация
AIM: Nocturnal exacerbation of pulpitis-induced 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-induced pain in mice and the role of clock genes in its nocturnal exacerbation.
METHODOLOGY: An experimental pulpitis model was established via pulp exposure, with stability confirmed by Micro-computed tomography and haematoxylin and eosin staining. Von Frey test was used to investigate the circadian characteristics of pulpitis-induced pain. Immunofluorescence (IF) staining, in vivo 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-induced pain. Single-nuclei RNA sequencing (snRNA-seq) was performed to screen differentially expressed genes. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and IF staining were used to detect the expression changes and neuronal expression profile of brain and muscle ARNT-like protein 1 (BMAL1). Adeno-associated virus selectively overexpressed BMAL1 in pyramidal neurons was constructed. Combined with behavioural tests, Western blot, and in vivo fibre photometry, the role and underlying mechanism of BMAL1 in the nocturnal exacerbation of pulpitis-induced pain were evaluated.
RESULT: 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-induced pain. Using snRNA-seq, qRT-PCR, 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-induced pain, alongside decreased activation of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling pathway and reduced pyramidal neuronal excitability.
CONCLUSION: 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.
METHODOLOGY: An experimental pulpitis model was established via pulp exposure, with stability confirmed by Micro-computed tomography and haematoxylin and eosin staining. Von Frey test was used to investigate the circadian characteristics of pulpitis-induced pain. Immunofluorescence (IF) staining, in vivo 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-induced pain. Single-nuclei RNA sequencing (snRNA-seq) was performed to screen differentially expressed genes. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and IF staining were used to detect the expression changes and neuronal expression profile of brain and muscle ARNT-like protein 1 (BMAL1). Adeno-associated virus selectively overexpressed BMAL1 in pyramidal neurons was constructed. Combined with behavioural tests, Western blot, and in vivo fibre photometry, the role and underlying mechanism of BMAL1 in the nocturnal exacerbation of pulpitis-induced pain were evaluated.
RESULT: 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-induced pain. Using snRNA-seq, qRT-PCR, 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-induced pain, alongside decreased activation of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling pathway and reduced pyramidal neuronal excitability.
CONCLUSION: 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.