Diminished neurokinin-1 receptor availability in patients with two forms of chronic visceral pain.

Abstract

Central sensitization and dysregulation of peripheral substance P and neurokinin-1 receptor (NK-1R) signaling are associated with chronic abdominal pain in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Although positron emission tomography (PET) has demonstrated that patients with injury-related chronic pain have diminished NK-1R availability in the brain, it is unknown whether these deficits are present in IBD and IBS patients, who have etiologically distinct forms of non-injury-related chronic pain. This study's aim was to determine if patients with IBD or IBS exhibit deficits in brain expression of NK-1Rs relative to healthy controls (HCs), the extent to which expression patterns differ across patient populations, and if these patterns differentially relate to clinical parameters. PET with [(18)F]SPA-RQ was used to measure NK-1R availability by quantifying binding potential (BP) in the 3 groups. Exploratory correlation analyses were performed to detect associations between NK-1R BP and physical symptoms. Compared to HCs, IBD patients had NK-1R BP deficits across a widespread network of cortical and subcortical regions. IBS patients had similar, but less pronounced deficits. BP in a subset of these regions was robustly related to discrete clinical parameters in each patient population. Widespread deficits in NK-1R BP occur in IBD and, to a lesser extent, IBS; however, discrete clinical parameters relate to NK-1R BP in each patient population. This suggests that potential pharmacological interventions that target NK-1R signaling may be most effective for treating distinct symptoms in IBD and IBS.

• Authors: Johanna M Jarcho, Natasha A Feier, Alberto Bert, Jennifer A Labus, Maunoo Lee, Jean Stains, Bahar Ebrat, Stephanie M Groman, Kirsten Tillisch, Arthur L Brody, Edythe D London, Mark A Mandelkern, Emeran A Mayer
• Journal: Pain (Pain) Vol. 154 Issue 7 Pg. 987-96 (Jul 2013) ISSN: 1872-6623 [Electronic] United States
• PMID: 23582152 (Publication Type: Comparative Study, Controlled Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Chemical References

• Receptors, Neurokinin-1

Topics

• Adult
• Brain (metabolism)
• Chronic Pain
• Down-Regulation
• Female
• Humans
• Inflammatory Bowel Diseases (metabolism)
• Irritable Bowel Syndrome (metabolism)
• Male
• Pilot Projects
• Receptors, Neurokinin-1 (metabolism)
• Tissue Distribution
• Visceral Pain (metabolism)