title: 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.affiliation: Section on Developmental and Affective Neuroscience, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Jarcho
authors.forename: Natasha A
authors.initials: NA
authors.lastname: Feier
authors.forename: Alberto
authors.initials: A
authors.lastname: Bert
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Labus
authors.forename: Maunoo
authors.initials: M
authors.lastname: Lee
authors.forename: Jean
authors.initials: J
authors.lastname: Stains
authors.forename: Bahar
authors.initials: B
authors.lastname: Ebrat
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Groman
authors.forename: Kirsten
authors.initials: K
authors.lastname: Tillisch
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Brody
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mandelkern
authors.forename: Emeran A
authors.initials: EA
authors.lastname: Mayer
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism*; D059350:Chronic Pain; D015536:Down-Regulation; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D043183:Irritable Bowel Syndrome / Q000378:metabolism*; D008297:Male; D010865:Pilot Projects; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D014018:Tissue Distribution; D059265:Visceral Pain / Q000378:metabolism*
chemical_list: D018040:Receptors, Neurokinin-1