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.

Conflict of interest statement

Conflict of interest statement: The authors report no conflict of interest.

Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1

Average whole-brain neurokinin-1 receptor binding potential across all participants.

Fig. 2

Whole-brain voxel-wise statistical parametric mapping analysis depicting regions with lower levels of neurokinin-1 receptor binding in inflammatory bowel disease (IBD) (A) and irritable bowel syndrome (IBS) patients (B), relative to healthy controls (voxel extent threshold P < 0.001; cluster extent threshold > 20).