Mocci Evelina, Goto Taichi, Chen Jie, Ament Seth, Traub Richard J, Dorsey Susan G
Department of Pain and Translational Symptom Science, University of Maryland School of Nursing, University of Maryland Baltimore, Baltimore, MD, United States.
Institute for Genome Sciences, University of Maryland School of Medicine, University of Maryland Baltimore, Baltimore, MD, United States.
Front Pain Res (Lausanne). 2022 May 17;3:886042. doi: 10.3389/fpain.2022.886042. eCollection 2022.
Irritable bowel syndrome (IBS) and temporomandibular disorder (TMD) are two chronic pain conditions that frequently overlap in the same individual, more commonly in women. Stress is a significant risk factor, exacerbating or triggering one or both conditions. However, the mechanisms underlying IBS-TMD co-morbidity are mostly unknown.
To detect both specific and common stress-induced visceral hypersensitivity (SIH) and comorbid TMD-IBS pain hypersensitivity (CPH) genetic signatures over time.
Twenty-four female rats were randomly assigned to one of three experimental groups: naïve, SIH, and CPH (orofacial pain plus stress). RNA was extracted from blood, colon, spinal cord, and dorsal root ganglion 1 or 7 weeks after the stress paradigm. We combined differential gene expression and co-expression network analyses to define both SIH and CPH expression profiles across tissues and time.
The transcriptomic profile in blood and colon showed increased expression of genes enriched in inflammatory and neurological biological processes in CPH compared to SIH rats, both at 1 and 7 weeks after stress. In lumbosacral spinal tissue, both SIH and CPH rats compared to naïve revealed decreased expression of genes related to synaptic activity and increased expression of genes enriched in "angiogenesis," "Neurotrophin," and "PI3K-Akt" pathways. Compared to SIH, CPH rats showed increased expression of angiogenesis-related genes 1 week after exposure to stress, while 7 weeks post-stress the expression of these genes was higher in SIH rats. In dorsal root ganglia (DRG), CPH rats showed decreased expression of immune response genes at week 1 and inhibition of nerve myelination genes at 7 weeks compared to naïve. For all tissues, we observed higher expression of genes involved in ATP production in SIH compared to CPH at 1 week and this was reversed 7 weeks after the induction of stress.
Our study highlights an increased inflammatory response in CPH compared to SIH rats in the blood and colon. DRG and spinal transcriptomic profiles of both CPH and SIH rats showed inhibition of synaptic activity along with activation of angiogenesis. Targeting these biological processes may lead to a more profound understanding of the mechanisms underlying IBS-TMD comorbidities and new diagnostic and therapeutic strategies.
肠易激综合征（IBS）和颞下颌关节紊乱病（TMD）是两种慢性疼痛病症，常出现在同一个体中，在女性中更为常见。压力是一个重要的风险因素，会加重或引发其中一种或两种病症。然而，IBS - TMD共病的潜在机制大多尚不清楚。
随着时间推移，检测特定的和共同的应激诱导内脏超敏反应（SIH）以及共病的TMD - IBS疼痛超敏反应（CPH）的基因特征。
将24只雌性大鼠随机分为三个实验组之一：未处理组、SIH组和CPH组（口面部疼痛加应激）。在应激模式后1周或7周，从血液、结肠、脊髓和背根神经节提取RNA。我们结合差异基因表达分析和共表达网络分析，以确定不同组织和时间的SIH和CPH表达谱。
与SIH大鼠相比，应激后1周和7周时，CPH大鼠血液和结肠中的转录组谱显示，参与炎症和神经生物学过程的基因表达增加。在腰骶部脊髓组织中，与未处理组相比，SIH组和CPH组大鼠与突触活动相关的基因表达均降低，而参与“血管生成”“神经营养因子”和“PI3K - Akt”通路的基因表达增加。与SIH组相比，CPH组大鼠在暴露于应激后1周时血管生成相关基因的表达增加，而在应激后7周时，这些基因在SIH组大鼠中的表达更高。在背根神经节（DRG）中，与未处理组相比，CPH组大鼠在第1周时免疫反应基因的表达降低，在第7周时神经髓鞘形成基因受到抑制。对于所有组织，我们观察到在应激诱导后1周时，与CPH组相比，SIH组中参与ATP生成的基因表达更高，而在7周后这种情况发生了逆转。
我们的研究强调，与SIH大鼠相比，CPH大鼠在血液和结肠中的炎症反应增强。CPH组和SIH组大鼠的DRG和脊髓转录组谱均显示突触活动受到抑制，同时血管生成被激活。针对这些生物学过程可能会更深入地了解IBS - TMD共病的潜在机制，并带来新的诊断和治疗策略。
