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 [18F]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.
Bibliographical noteFunding Information:
This work was supported in part by National Institutes of Health Grants F31-DA021951 , T32-MH017140 (J.M.J.), F31-DA028812 (S.M.G.), NIH AT00268 (E.A.M.), and endowments from the Marjorie Greene Family Trust and National Institute on Drug Abuse (A.L.B. [R01 DA20872]), the Tobacco-Related Disease Research Program (A.L.B. [19XT-0135]), the Department of Veterans Affairs, Office of Research and Development (Merit Review Award [A.L.B.]), and the Thomas P. and Katherine K. Pike Chair in Addiction Studies (E.D.L.).
- Inflammatory bowel disease
- Irritable bowel syndrome
- NK-1 receptor
- Quality of life
- Somatic pain