Characterizing clinical features and location‐specific gene expression profiles associated with pain burden in children with functional dyspepsia

Abstract

Background In children with functional dyspepsia (FD), genes involved in pain modulation may be differentially expressed contributing to chronic pain. Methods Children with suspected FD (cases) and known eosinophilic esophagitis (controls) undergoing esophagogastroduodenoscopy completed the Rome IV Diagnostic, Pain Burden and Frequency Severity‐Duration questionnaires. Two antral and two duodenal biopsies were collected and relative fold differences in gene expression for 84 pain‐associated genes compared to pain‐free controls were calculated. Results Sixty‐six subjects with FD (postprandial distress syndrome = 34, epigastric pain syndrome = 7, both = 25; 65% female; mean age 13.7 years) and 13 pain‐free controls (8% female; mean age 12.7) were studied. There were no significant differences in antral and duodenal eosinophilic counts or distribution between the pain and pain‐free groups. Pain severity and burden did not differ significantly between FD subgroups and neither measure significantly correlated with eosinophil counts in the antrum or duodenum. Analysis of 47 antral and 39 duodenal biospecimens revealed 5 candidate genes significantly associated with pain burden: antral EDN1, PTGES3 and duodenal HTR1A, P2Y1, SCN3A (p < 0.01). Subsequent stringent statistical analysis comparing those with significant pain versus no pain revealed antral PTGES3 and duodenal SCN3A were the highest priority candidate genes (p < 0.001). Conclusions Pain burden in pediatric FD may be linked to antral EDN1, PTGES3 and duodenal HTR1A, P2Y1, SCN3A differential expression. These genes are known to be involved in pain conduction, modulation, and neurotransmission, suggesting potential therapeutic targets for managing pain in FD.

Effect of PTGES3 on the Prognosis and Immune Regulation in Lung Adenocarcinoma

“…Prostaglandin, produced in a COX2-dependent manner, could act on the epithelium to regulate intravasation and immune cell function in malignant cells [16,17]. Previous studies have revealed that PTGES3 participates in the regulation of various diseases, including pediatric recurrent abdominal pain, oscillatory shear stress, dyspepsia, and cancers [18][19][20]. In recent years, there has been an increasing interest in the tumorigenic role of PTGES3 in multiple cancer types, including colorectal cancer, prostate cancer, and acute lymphoblastic leukemia [8,22].…”

Mutations in Hsp90 Cochaperones Result in a Wide Variety of Human Disorders

“…In some cases, additional cochaperones are also known to interact with some of those listed. For example, the GR is one of the most widely studied Hsp90 clients, and changes in activity of GR and/or other clients due to altered abundance of associated cochaperones has been linked to mood disorders, autism, anxiety, psychotic illness, depression, and altered pain susceptibility ( Sinclair et al, 2013 ; Patel et al, 2016 ; Baker et al, 2018 ; Lee et al, 2019 ; Lou et al, 2021 ; Mokha et al, 2021 ; Salhi et al, 2021 ; Szczepankiewicz et al, 2021 ). Similarly, androgen receptor activity is highly dependent on cochaperones encoded by FKBP4, FKBPL, and SGTA ( Paul et al, 2014 ; Ilaslan et al, 2020 ; Sengun et al, 2021 ).…”

Gene Expression Profiling in Coeliac Disease Confirmed the Key Role of the Immune System and Revealed a Molecular Overlap with Non-Celiac Gluten Sensitivity

“…However, as analysed in a recent systematic review [24], no consistent association was found between most of the reported gene polymorphisms and FD. Moreover, a recent gene expression profiling study, conducted on duodenal biopsies of children, identified three candidate genes associated with FD pain [25]. Given the lack of major measurable molecular changes in FD, these patients represented a good control for our study.…”