Neurokinin‐1‐receptor antagonism decreases anxiety and emotional arousal circuit response to noxious visceral distension in women with irritable bowel syndrome: a pilot study
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Summary: Background Irritable bowel syndrome is characterised by chronic abdominal pain and frequent comorbid anxiety. The substance P/neurokinin‐1 receptor system is implicated in the regulation of both pain and anxiety, suggesting a potential therapeutic target in IBS. Aim To determine whether inhibition of the neurokinin‐1 receptor (NK1R) will change pain ratings and brain responses to experimental visceral pain and anxiety symptoms in women with IBS or not. Methods Rome II positive IBS women were recruited for a double‐blind, placebo‐controlled, cross‐over study of NK1R antagonist AV608. Treatment periods were 3 weeks with a 2‐week washout period. Functional MRI during a visceral distension paradigm was performed before first treatment and after treatment blocks. SPM8 was used to compare brain activity during painful and nonpainful visceral stimuli in regions associated with emotional arousal and interoception. Negative affect, anxiety symptoms and pain ratings were assessed. Results Eleven subjects completed the study and eight subjects provided fMRI data. AV608, compared with placebo, was associated with reduced anxiety, negative affect, and pain ratings. During AV608 treatment, the amygdala, hippocampus and anterior cingulate gyrus showed decreased activity during visceral distension. AV608 was also associated with decreases in activity in brain regions associated with interoception (posterior insula, anterior mid‐cingulate gyrus). Conclusions Chronic treatment with AV608 in IBS is associated with improved mood and pain ratings and activity of emotional arousal related brain regions. This suggests that further exploration of NK1R antagonists is warranted in visceral pain disorders, particularly in patients with comorbid anxiety symptoms.
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NK1R antagonism reduces anxiety and emotional arousal circuit response to noxious visceral distension in women with irritable bowel syndrome.
“Moreover, NK1R antagonism has been shown to reduce anxiety and emotional arousal circuit response to noxious visceral distension in women with irritable bowel syndrome107, which is likely attributable, at least in part, to increased colonic hypermotility induced by SP and NK1R activation72,73.”
From Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis (2019) · cites this paper as [107]
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- Authors
- Tillisch, K., Labus, J., Nam, B., Bueller, J., Smith, S., Suyenobu, B., Siffert, J., McKelvy, J., Naliboff, B., & Mayer, E.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Tillisch, K.
- Venue
- Alimentary Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2012-01-03
- Volume
- 35
- Issue
- 3
- Pages
- 360-367
- ISSN
- 0269-2813 (ISSN-L)
- 1365-2036
- PMC
- PMC4073664
- OpenAlex
- W1943020141
- Semantic Scholar
- 36efa1731df2264c38b6d1bcdddda6ed8310c039
- Cited by
- 60
- References
- 40
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 9 · 2013: 10 · 2012: 8
- FWCI
- 9.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Alimentary Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Danone
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK071626, K23DK073451)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- irritable bowel syndrome, substance P, visceral pain, anxiety, emotional arousal, amygdala, hippocampus, anterior cingulate cortex, interoception, posterior insula, negative affect, women
- MeSH terms
- Adolescent, Adult, Aged, Anxiety, Arousal, Dilatation, Pathologic, Double-Blind Method, Emotions, Female, Humans, Middle Aged, Pain, Pain Measurement, Pilot Projects, Piperidines, Stress, Psychological, Abdominal Pain, Pain Threshold, Receptors, Neurokinin-1, Cross-Over Studies, Irritable Bowel Syndrome, Young Adult, Visceral Pain, Neurokinin-1 Receptor Antagonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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