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

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

Research output: Contribution to journalArticlepeer-review

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 [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.

Original languageEnglish (US)
Pages (from-to)987-996
Number of pages10
JournalPain
Volume154
Issue number7
DOIs
StatePublished - Jul 2013
Externally publishedYes

Bibliographical note

Funding 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.).

Keywords

  • Inflammatory bowel disease
  • Irritable bowel syndrome
  • NK-1 receptor
  • PET
  • Quality of life
  • Somatic pain

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