Gene expression profiles in peripheral blood mononuclear cells correlate with salience network activity in chronic visceral pain: A pilot study

• Published in: Neurogastroenterology and motility Vol. 29; no. 6
• Main Authors: Gupta, A., Cole, S., Labus, J. S., Joshi, S., Nguyen, T. J., Kilpatrick, L. A., Tillisch, K., Naliboff, B. D., Chang, L., Mayer, E. A.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.06.2017
• Subjects: Adult; anti‐inflammatory genes; Anxiety; Brain - physiopathology; Brain Mapping; Chronic pain; Chronic Pain - genetics; Chronic Pain - physiopathology; chronic visceral pain syndrome; Cortex (cingulate); Cortex (temporal); Digestive tract; Female; Gene expression; Humans; immune system; Inflammation; Inflammation - genetics; Inflammation Mediators - metabolism; Interleukin 6; Intestine; Irritable bowel syndrome; Irritable Bowel Syndrome - genetics; Irritable Bowel Syndrome - physiopathology; Leukocyte migration; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Magnetic Resonance Imaging; Male; Monocytes; Multivariate analysis; Peripheral blood mononuclear cells; Pilot Projects; pro‐inflammatory genes; resting state brain activity; salience network; Stress; Superior temporal gyrus; Sympathetic nervous system; Temporal gyrus; Transcriptome; Vagus nerve; Visceral Pain - genetics; Visceral Pain - physiopathology; anti-inflammatory genes; chronic visceral pain syndrome; peripheral blood mononuclear cells; resting state brain activity; salience network; immune system; pro-inflammatory genes
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.13027

Background Distinct gene expression profiles in peripheral blood mononuclear cells (PBMCs) consistent with increased sympathetic nervous system activity have been described in different populations under chronic stress. Neuroinflammatory brain changes, possibly related to the migration of primed monocytes to the brain, have been implicated in the pathophysiology of chronic pain. Irritable bowel syndrome (IBS) is a stress‐sensitive gastrointestinal disorder associated with altered brain‐gut interactions and increased sympathetic/vagal tone and anxiety. Reports about immune alterations in IBS are conflicting. This pilot study aimed to test how PBMC gene expression inflammatory profiles are correlated with altered brain signatures in the salience system. Methods Sixteen IBS and 16 healthy controls (HCs) completed resting state MRI scans. Gene expression profiles in PBMCs were assessed using human transcriptome array‐2. Bioinformatic analyses determined differential expression of PBMCs between IBS and HCs. Partial least squares, a multivariate analysis technique, was used to identify disease correlations between PBMC gene expression profiles and functional activity in the brain's salience network. Key Results Regions of the salience network, including the mid cingulate cortex, and mid and superior temporal gyrus were positively correlated with several pro‐inflammatory genes (interleukin 6, APOL2) in IBS, but negatively correlated with several anti‐inflammatory genes (KRT8, APOA4) in HCs. Conclusions & Inferences Based on rodent studies, one may speculate that chronically activated stress signaling pathways in IBS maintain a pro‐inflammatory state in the periphery. Alternatively, primed monocytes may migrate to the brain during stress, inducing regional neuroinflammatory changes in salience regions involved in the modulation of visceral sensitivity. Results show a difference in correlation between PBMC gene expression levels and salience network connectivity in patients with IBS vs. HCs. Inflammatory genes (IL6 and APOL2) are positively correlated with connectivity within salience network in IBS patients (strengthened connectivity). Genes with anti‐inflammatory properties (KRT8, APOA4, KRT8A) and 1 inflammatory gene (APOL2) are negatively correlated with connectivity within salience network in HCs (weakened connectivity.