Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
PLoS One. 2023 Sep 21;18(9):e0291724. doi: 10.1371/journal.pone.0291724. eCollection 2023.
Dental pain from apical periodontitis is an infection induced-orofacial pain condition that presents with diversity in pain phenotypes among patients. While 60% of patients with a full-blown disease present with the hallmark symptom of mechanical allodynia, nearly 40% of patients experience no pain. Furthermore, a sexual dichotomy exists, with females exhibiting lower mechanical thresholds under basal and diseased states. Finally, the prevalence of post-treatment pain refractory to commonly used analgesics ranges from 7-19% (∼2 million patients), which warrants a thorough investigation of the cellular changes occurring in different patient cohorts. We, therefore, conducted a transcriptomic assessment of periapical biopsies (peripheral diseased tissue) from patients with persistent apical periodontitis. Surgical biopsies from symptomatic male (SM), asymptomatic male (AM), symptomatic female (SF), and asymptomatic female (AF) patients were collected and processed for bulk RNA sequencing. Using strict selection criteria, our study found several unique differentially regulated genes (DEGs) between symptomatic and asymptomatic patients, as well as novel candidate genes between sexes within the same pain group. Specifically, we found the role of cells of the innate and adaptive immune system in mediating nociception in symptomatic patients and the role of genes involved in tissue homeostasis in potentially inhibiting nociception in asymptomatic patients. Furthermore, sex-related differences appear to be tightly regulated by macrophage activity, its secretome, and/or migration. Collectively, we present, for the first time, a comprehensive assessment of peripherally diseased human tissue after a microbial insult and shed important insights into the regulation of the trigeminal system in female and male patients.
根尖周炎引起的牙痛是一种感染性的颌面疼痛疾病，患者的疼痛表型存在多样性。虽然 60%的完全发病患者表现出机械性超敏反应的标志性症状，但近 40%的患者没有疼痛。此外，还存在性别二态性，基础状态和患病状态下女性的机械阈值较低。最后，治疗后对常用镇痛药产生疼痛的患者比例为 7-19%（约 200 万患者），这需要对不同患者群体中发生的细胞变化进行深入研究。因此，我们对持续性根尖周炎患者的根尖活检（外周患病组织）进行了转录组评估。从有症状的男性（SM）、无症状的男性（AM）、有症状的女性（SF）和无症状的女性（AF）患者中采集手术活检，并进行批量 RNA 测序。使用严格的选择标准，我们的研究发现了几个在有症状和无症状患者之间以及在同一疼痛组中男女之间独特的差异调节基因（DEGs）。具体来说，我们发现了先天和适应性免疫系统细胞在介导有症状患者的疼痛感知中的作用，以及参与组织稳态的基因在无症状患者中可能抑制疼痛感知的作用。此外，性别相关的差异似乎受到巨噬细胞活性、其分泌组和/或迁移的严格调节。总的来说，我们首次对微生物感染后的外周患病人类组织进行了全面评估，并深入了解了女性和男性患者三叉神经系统的调节。
