King Christopher D, Boggero Ian A, Schulert Grant S, Pickerill Hannah M, Cole Steve
Center for Understanding Pediatric Pain (CUPP), Cincinnati Children's, Cincinnati, OH, USA.
Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's, Cincinnati, OH, USA.
Pain Rep. 2021 Jan 8;6(1):e874. doi: 10.1097/PR9.0000000000000874. eCollection 2021 Jan-Feb.
Temporomandibular disorder (TMD) is one of the most common orofacial pain conditions. Alteration in immune functioning is one promising biological mechanism underlying pain in TMD. However, there is a gap in the understanding of molecular bases contributing to altered immune functioning in these patients.
In the current study, we investigated whether individuals with TMD would exhibit differential activity of 3 specific transcription factors involved in inflammatory (nuclear factor-kappa B, NF-kB), antiviral (interferon-regulatory factors, IRF), and sympathetic (cAMP response element-binding protein, CREB) processes using a promoter-based bioinformatics analysis, which is characterized as the "Conserved Transcriptional Response to Adversity."
Adults with TMD (n = 19) and without (n = 17) underwent a standardized clinical examination for TMD. A blood sample was collected for genome-wide transcriptional RNA profiling. Bioinformatic analyses tested for differential prevalence of proinflammatory and antiviral transcription factor activity in core promoter sequences from all genes showing >1.2-fold differential expression in TMD vs controls.
Promoter-based bioinformatic analyses of genome-wide transcriptome profiles confirmed upregulation of genes bearing response elements for proinflammatory transcription factor (NF-kB, = 0.002) and downregulation of genes with response elements for IRF ( = 0.037) in patients with TMD relative to controls. Results also indicated upregulated activity of CREB in patients with TMD ( = 0.08), consistent with increased activity of the sympathetic nervous system.
These results provide initial support that the regulation of immune pathways is altered in individuals with TMD. A shift of transcriptional resources to a proinflammatory state may be driven by psychosocial stress and contributes to symptoms associated with TMD.
颞下颌关节紊乱病（TMD）是最常见的口腔面部疼痛病症之一。免疫功能改变是TMD疼痛潜在的一种有前景的生物学机制。然而，对于导致这些患者免疫功能改变的分子基础的理解仍存在差距。
在本研究中，我们使用基于启动子的生物信息学分析（其特征为“对逆境的保守转录反应”），调查患有TMD的个体是否会表现出参与炎症（核因子-κB，NF-κB）、抗病毒（干扰素调节因子，IRF）和交感神经（cAMP反应元件结合蛋白，CREB）过程的3种特定转录因子的差异活性。
患有TMD（n = 19）和未患TMD（n = 17）的成年人接受了TMD的标准化临床检查。采集血样用于全基因组转录RNA分析。生物信息学分析测试了在TMD与对照组中显示>1.2倍差异表达所有基因的核心启动子序列中促炎和抗病毒转录因子活性的差异发生率。
基于启动子的全基因组转录组谱生物信息学分析证实，与对照组相比，TMD患者中带有促炎转录因子反应元件的基因上调（P = 0.002），带有IRF反应元件的基因下调（P = 0.037）。结果还表明TMD患者中CREB活性上调（P = 0.08），这与交感神经系统活性增加一致。
这些结果提供了初步支持，即TMD患者的免疫途径调节发生改变。转录资源向促炎状态的转变可能由心理社会压力驱动，并导致与TMD相关的症状。
