Histamine Receptor H1–Mediated Sensitization of TRPV1 Mediates Visceral Hypersensitivity and Symptoms in Patients With Irritable Bowel Syndrome
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Background & aims Histamine sensitizes the nociceptor transient reporter potential channel V1 (TRPV1) and has been shown to contribute to visceral hypersensitivity in animals. We investigated the role of TRPV1 in irritable bowel syndrome (IBS) and evaluated if an antagonist of histamine receptor H1 (HRH1) could reduce symptoms of patients in a randomized placebo-controlled trial.Methods By using live calcium imaging, we compared activation of submucosal neurons by the TRPV1 agonist capsaicin in rectal biopsy specimens collected from 9 patients with IBS (ROME 3 criteria) and 15 healthy subjects. The sensitization of TRPV1 by histamine, its metabolite imidazole acetaldehyde, and supernatants from biopsy specimens was assessed by calcium imaging of mouse dorsal root ganglion neurons. We then performed a double-blind trial of patients with IBS (mean age, 31 y; range, 18-65 y; 34 female). After a 2-week run-in period, subjects were assigned randomly to groups given either the HRH1 antagonist ebastine (20 mg/day; n = 28) or placebo (n = 27) for 12 weeks. Rectal biopsy specimens were collected, barostat studies were performed, and symptoms were assessed (using the validated gastrointestinal symptom rating scale) before and after the 12-week period. Patients were followed up for an additional 2 weeks. Abdominal pain, symptom relief, and health-related quality of life were assessed on a weekly basis. The primary end point of the study was the effect of ebastine on the symptom score evoked by rectal distension.Results TRPV1 responses of submucosal neurons from patients with IBS were potentiated compared with those of healthy volunteers. Moreover, TRPV1 responses of submucosal neurons from healthy volunteers could be potentiated by their pre-incubation with histamine; this effect was blocked by the HRH1 antagonist pyrilamine. Supernatants from rectal biopsy specimens from patients with IBS, but not from the healthy volunteers, sensitized TRPV1 in mouse nociceptive dorsal root ganglion neurons via HRH1; this effect could be reproduced by histamine and imidazole acetaldehyde. Compared with subjects given placebo, those given ebastine had reduced visceral hypersensitivity, increased symptom relief (ebastine 46% vs placebo 13%; P = .024), and reduced abdominal pain scores (ebastine 39 ± 23 vs placebo 62 ± 22; P = .0004).Conclusions In studies of rectal biopsy specimens from patients, we found that HRH1-mediated sensitization of TRPV1 is involved in IBS. Ebastine, an antagonist of HRH1, reduced visceral hypersensitivity, symptoms, and abdominal pain in patients with IBS. Inhibitors of this pathway might be developed as a new treatment approach for IBS. ClinicalTrials.gov no: NCT01144832.
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In a small RCT in 45 patients, the histamine 1 receptor antagonist ebastine led to significant improvements in both abdominal pain and global symptoms.
“in a small RCT in 45 patients the histamine 1 receptor antagonist ebastine led to significant improvements in both abdominal pain and global symptoms.290”
From British Society of Gastroenterology guidelines on the management of irritable bowel syndrome (2021) · cites this paper as [290]
The trial-results section reports significantly greater global symptom relief and lower abdominal pain scores with ebastine than with placebo at week 12. The stated trial size is incorrect: 55 patients were randomized, not 45 (51 completed treatment). No page number is available in our copy. (LLM, conf=0.92)
Experimental — accuracy not yet measuredThese mast cell mediators may alter nociceptive pathways in IBS or increase intestinal permeability.
“These mediators may alter nociceptive pathways in IBS115 or increase intestinal permeability116.”
From The gut Microbiome in adult and pediatric functional gastrointestinal disorders (2019) · cites this paper as [115]
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Irritable bowel syndrome: treatment based on pathophysiology and biomarkers
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Food allergy as a biological food quality control system
Florsheim, E. B., Sullivan, Z. A., Khoury-Hanold, W., & Medzhitov, R. M. (2021) · Cell · doi:10.1016/j.cell.2020.12.007 · Cited by 113 · see citing works
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Can we ‘seize’ the gut microbiota to treat epilepsy?
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Mast cell mediation of visceral sensation and permeability in irritable bowel syndrome
Hasler, W. L., Grabauskas, G., Singh, P., & Owyang, C. (2022) · Neurogastroenterology & Motility · doi:10.1111/nmo.14339 · Cited by 105 · see citing works
Immune activation in irritable bowel syndrome: what is the evidence?
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“Peripheral sensitization may contribute with similar mechanisms of sensitization observed in IBS as to those seen in EAP, including increased activation of the TRPV1 receptor (107).”
BackgroundLuo, J., Qian, A., Oetjen, L. K., Yu, W., Yang, P., Feng, J., Xie, Z., Liu, S., Yin, S., Dryn, D. O., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.04.021 · Cited by 97 · see citing works
“A subset of TRP channels are expressed in the gut and have been shown to regulate GI motility under both steady-state and pathological conditions (Cenac et al., 2015; Tsvilovskyy et al., 2009; Wouters et al., 2016).”
Modulation of TRPV1 channel function by natural products in the treatment of pain
Abbas, M. A. (2020) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2020.109178 · Cited by 95 · see citing works
Effect of resolvins on sensitisation of TRPV1 and visceral hypersensitivity in IBS
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Self-citationMolecular Mechanisms of Microbiota-Mediated Pathology in Irritable Bowel Syndrome
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Neuroimmune Interactions in the Intestine
Wallrapp, A., & Chiu, I. M. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101921-042929 · Cited by 91 · see citing works
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“Wouters and coauthors revealed that such a sensitization could be mediated by histamine H1 receptors; thus, their inhibitors are investigated further as a new therapeutic strategy [106].”
BackgroundFood Intolerance: The Role of Histamine
Shulpekova, Y. O., Nechaev, V. M., Popova, I. R., Deeva, Т. A., Kopylov, A. T., Malsagova, K. A., Kaysheva, A. L., & Ivashkin, V. T. (2021) · Nutrients · doi:10.3390/nu13093207 · Cited by 88 · see citing works
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“As this effect was also mediated via activation of the Hrh1 (128), we speculate that mediators released by immune cells, most likely mast cells, in the submucosa trigger TRP sensitization and neuronal hypersensitivity.”
InfluentialSelf-citationManagement of the multiple symptoms of irritable bowel syndrome
Simrén, M., Törnblom, H., Palsson, O. S., & Whitehead, W. E. (2017) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(16)30116-9 · Cited by 82 · see citing works
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Chronic Visceral Pain: New Peripheral Mechanistic Insights and Resulting Treatments
Ford, A. C., Vanner, S. J., Kashyap, P., & Nasser, Y. (2024) · Gastroenterology · doi:10.1053/j.gastro.2024.01.045 · Cited by 79 · see citing works
Self-citationCastro, J., Harrington, A. M., Lieu, T., Garcia‐Caraballo, S., Maddern, J., Schober, G., O’Donnell, T. A., Grundy, L., Lumsden, A. L., Miller, P. E., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.131712 · Cited by 78 · see citing works
“Conversely, histamine-dependent mechanisms in the colon contribute to afferent sensitization via TRPV1-dependent (12) and TRPV4-dependent (47) mechanisms, potentially suggesting divergent mechanisms between hista-mine-dependent and histamine-independent afferent sensitization.”
Enteric Glia: A New Player in Abdominal Pain
Morales‐Soto, W., & Gulbransen, B. D. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.11.005 · Cited by 78 · see citing works
Tait, C., & Sayuk, G. S. (2021) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2020.12.023 · Cited by 78 · see citing works
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The gut microbiome in disorders of gut–brain interaction
Kraïmi, N., Ross, T., Pujo, J., & Palma, G. D. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2360233 · Cited by 86 · see citing works
Current insights into the innate immune system dysfunction in irritable bowel syndrome
Lazaridis, N. (2018) · Annals of Gastroenterology · doi:10.20524/aog.2018.0229 · Cited by 75 · see citing works
“Contrariwise, ebastine, an antagonist of histamine receptor H1, improved both visceral hypersensitivity and symptom discomfort in a proof-of-principle pilot study with 55 Rome III IBS patients, compared with placebo [69].”
BackgroundNeurons and Glia in the Enteric Nervous System and Epithelial Barrier Function
Vergnolle, N., & Cirillo, C. (2018) · Physiology · doi:10.1152/physiol.00009.2018 · Cited by 106 · see citing works
Self-citationKennedy, L. L., Hargrove, L. A., Demieville, J., Karstens, W., Jones, H. F., DeMorrow, S., Meng, F., Invernizzi, P., Bernuzzi, F., Alpini, G. D., et al. (2018) · Hepatology · doi:10.1002/hep.29898 · Cited by 71 · see citing works
“(33) Patients using ketotifen to block H1HR received relief from IBS symptoms including a reduction in abdominal pain; however, it was not clear if this drug also blocked MC activation.”
InfluentialRetractedMeynier, M., Daugey, V., Mallaret, G., Gervason, S., Méleine, M., Barbier, J., Aissouni, Y., Lolignier, S., Bonnet, M., Ardid, D., et al. (2024) · Gut Microbes · doi:10.1080/19490976.2023.2298026 · Cited by 66 · see citing works
“53 We therefore hypothesized that pas-teurized A. muciniphila treatment could directly modulate activation of the primary afferent fibers, alleviating colonic hypersensitivity in our in vivo IBS mouse models.”
Colitis-Induced Microbial Perturbation Promotes Postinflammatory Visceral Hypersensitivity
Esquerre, N., Basso, L., Defaye, M., Vicentini, F., Cluny, N. L., Bihan, D. G., Hirota, S. A., Schick, A., Jijon, H. B., Lewis, I. A., et al. (2020) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2020.04.003 · Cited by 67 · see citing works
“Thus, we exposed naive TRPexpressing DRG neurons to the nociceptive mediators present in the colon.(39) TRPV1 responses to 100 nmol/L capsaicin stimulation were significantly increased in naive colonic DRGs incubated with colonic supernatant derived from postinflammatory DSS mice compared with controls (area under the…”
MethodSelf-citationCeuleers, H., Spaendonk, H. V., Hanning, N., Heirbaut, J., Lambeir, A., Joossens, J., Augustyns, K., Man, J. G. D., Meester, I. D., & Winter, B. Y. D. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i47.10275 · Cited by 63 · see citing works
Balemans, D., Aguilera‐Lizarraga, J., Florens, M. V., Jain, P., Denadai‐Souza, A., Viola, M. F., Alpizar, Y. A., der Merwe, V., Berghe, P. V., Talavera, K., et al. (2019) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00116.2018 · Cited by 63 · see citing works
“Moreover, increased neuronal excitability of DRG neurons in response to IBS supernatant has been repeatedly reported (8, 13, 22, 38, 44).”
BackgroundMethodInfluentialSelf-citationGrundy, L., Caldwell, A., Garcia‐Caraballo, S., Erickson, A., Schober, G., Castro, J., Harrington, A. M., & Brierley, S. M. (2019) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00435.2019 · Cited by 61 · see citing works
Gut-innervating TRPV1+ Neurons Drive Chronic Visceral Pain via Microglial P2Y12 Receptor
Defaye, M., Abdullah, N. S., Iftinca, M., Hassan, A., Agosti, F., Zhang, Z., Cuménal, M., Zamponi, G. W., & Altier, C. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.12.012 · Cited by 60 · see citing works
“Enhanced microglia reactivity contributes to persistent pain in several preclinical pain models, including peripheral and spinal injury, peripheral inflammation, bone cancer pain, and colitis.7–11 During active colitis, activated microglia produce a large panel of proinflammatory mediators including interleukin-6 (IL-…”
BackgroundInfluentialEvidence for long-term sensitization of the bowel in patients with post-infectious-IBS
Balemans, D., Mondelaers, S. U., Cibert-Goton, V., Stakenborg, N., Aguilera-Lizarraga, J., Dooley, J., Liston, A., Bulmer, D. C., Vanden Berghe, P., Boeckxstaens, G. E., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-12618-7 · Cited by 60 · see citing works
Self-citationIs there a causal link between psychological disorders and functional gastrointestinal disorders?
Koloski, N. A., Holtmann, G., & Talley, N. J. (2020) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2020.1801414 · Cited by 65 · see citing works
Tervaert, J. W. C. (2018) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2019.01.003 · Cited by 61 · see citing works
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Krohn, I. K., Callebaut, I., Alpizar, Y. A., Steelant, B., Gerven, L. V., Skov, P. S., Kasran, A., Talavera, K., Wouters, M. M., Ceuppens, J. L., et al. (2017) · Allergy · doi:10.1111/all.13349 · Cited by 57 · see citing works
Self-citationKeshteli, A. H., Madsen, K. L., Mandal, R., Boeckxstaens, G. E., Berčík, P., Palma, G. D., Reed, D. E., Wishart, D. S., Vanner, S. J., & Dieleman, L. A. (2019) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15141 · Cited by 56 · see citing works
“It has recently been reported that visceral hypersensitivity, symptoms and abdominal pain in IBS patients were reduced following administration of a histamine receptor H1 antagonist.(50) In addition, improvement in IBS severity following a low FODMAP diet was associated with reduction of urinary histamine.”
BackgroundSelf-citationDuodenal inflammation: an emerging target for functional dyspepsia?
Wauters, L. I., Burns, G. L., Ceulemans, M., Walker, M. M., Vanuytsel, T., Keely, S., & Talley, N. J. (2020) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2020.1752181 · Cited by 56 · see citing works
“The H1receptor antagonist and mast cell-stabilizer ketotifen also improved visceral hypersensitivity, symptoms, and quality of life in IBS patients [77] and similar effects were reported with ebastine via reduction of H1-mediated sensitization of the transient receptor potential vanilloid receptor type 1 (TRPV1) [50].”
BackgroundInfluentialPhenotyping of subjects for large scale studies on patients with IBS
Boeckxstaens, G. E., Drug, V. L., Dumitrascu, D. L., Farmer, A. D., Hammer, J., Hausken, T., Niesler, B., Pohl, D., Pojskić, L., Polster, A. V., et al. (2016) · Neurogastroenterology & Motility · doi:10.1111/nmo.12886 · Cited by 56 · see citing works
Self-citationNakato, R., Manabe, N., Shimizu, S., Hanayama, K., Shiotani, A., Hata, J., & Haruma, K. (2017) · Digestion · doi:10.1159/000463382 · Cited by 54 · see citing works
Intestinal neuro-immune interactions: focus on macrophages, mast cells and innate lymphoid cells
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Self-citationTargeting Histamine Receptors in Irritable Bowel Syndrome: A Critical Appraisal
Fabisiak, A., Włodarczyk, J., Fabisiak, N., Storr, M., & Fichna, J. (2017) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm16203 · Cited by 54 · see citing works
“A recent study showed that by blocking H1R with ebastine, a second generation H1R antagonist, attenuation of visceral hypersensitivity and other IBS symptoms could be achieved.(39) Interestingly, the transient receptor potential vanilloid 1 (TRPV1) was found to be implicated in the process; either histamine alone or t…”
BackgroundInfluentialKamphuis, J. B. J., Guiard, B. P., Leveque, M., Olier, M., Jouanin, I., Yvon, S., Tondereau, V., Rivière, P., Guéraud, F., Chevolleau, S., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.10.037 · Cited by 53 · see citing works
Uranga, J. A., Martı́nez, V., & Abalo, R. (2020) · Molecules · doi:10.3390/molecules25184314 · Cited by 53 · see citing works
“gov identifier: NCT01144832), whose results were published in 2016 [87].”
BackgroundEx vivo study of human visceral nociceptors
McGuire, C., Boundouki, G., Hockley, J. R. F., Reed, D. E., Cibert‐Goton, V., Peiris, M., Kung, V., Broad, J., Aziz, Q., Chan, C. T., et al. (2016) · Gut · doi:10.1136/gutjnl-2016-311629 · Cited by 51 · see citing works
Self-citationLiu, J., Dai, Q., Qu, T., Ma, J., Lv, C., Wang, H., & Yu, Y. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106440 · Cited by 53 · see citing works
“VHS, a key pathophysiological mechanism underlying abdominal pain in IBS patients, can be induced by either upregulation or sensitization of hypersensitivity channels in IBS patients and VHS animal models (Anavi-Goffer and Coutts, 2003; Wouters et al., 2016a).”
BackgroundPharmacotherapy for Irritable Bowel Syndrome
Camilleri, M., & Ford, A. (2017) · Journal of Clinical Medicine · doi:10.3390/jcm6110101 · Cited by 44 · see citing works
“Histamine sensitizes TRPV1 on neurons from murine dorsal root ganglia and on human submucosal neurons in rectal biopsies via activation of H1 receptors [62].”
BackgroundThe gut–brain axis and pain signalling mechanisms in the gastrointestinal tract
Meerschaert, K. A., & Chiu, I. M. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-01017-9 · Cited by 53 · see citing works
“Mast cells can degranulate and release a range of factors, including histamine and tryptase, which have been shown to activate nociceptive neurons through histamine receptors (HRs) and protease-activated receptors (PARs), leading to increased visceral hypersensitivity 105–108 .”
Regulation of plasma histamine levels by the mast cell clock and its modulation by stress
Nakamura, Y., Ishimaru, K., Shibata, S., & Nakao, A. (2017) · Scientific Reports · doi:10.1038/srep39934 · Cited by 46 · see citing works
“Potentiation (sensitization) of cellular responses by histamine has been reported in patients with irritable bowel syndrome, in which pre-exposure of sensory neurons from the colon to histamine increases TRPV4-mediated intracellular signaling, thereby increasing visceral hypersensitivity 43 .”
Brunkwall, L., Ericson, U., Nilsson, P. M., Orho‐Melander, M., & Ohlsson, B. (2020) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.15104 · Cited by 46 · see citing works
Biomarkers as a diagnostic tool for irritable bowel syndrome: where are we?
Camilleri, M., Halawi, H., & Oduyebo, I. (2017) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2017.1288096 · Cited by 45 · see citing works
“However, it may conceivably help select patients with persistent evidence of visceral hypersensitivity who could benefit from targeted therapy with visceral analgesia, as shown with the histamine H1 receptor antagonist, ebastine, which has effects on the TRPV1 pain pathways [89].”
BackgroundBeckers, A. B., Weerts, Z. Z. R. M., Helyes, Z., Masclee, A., & Keszthelyi, D. (2017) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14294 · Cited by 45 · see citing works
“Moreover, Wouters et al demonstrated an increased Ca response and increased number of responding neurons to capsaicin in histamine pre-treated biopsy specimens of healthy volunteers.(34) Immunostaining showed co-expression of histamine receptor H1 (HRH1) and TRPV1 on submucosal neurons in both IBS patients and healthy…”
BackgroundExisting and Emerging Therapies for Managing Constipation and Diarrhea
Bharucha, A., Wouters, M., & Tack, J. (2017) · Current opinion in pharmacology (Print) · doi:10.1016/j.coph.2017.10.015 · Cited by 36 · see citing works
“[35,36] In a 12-week, double-blind, placebo-controlled study, the HRH1 receptor antagonist ebastine (20mg once daily) reduced visceral hypersensitivity, and improved symptoms, including abdominal pain, versus placebo.[35] (Table 1).”
BackgroundSelf-citationLucarini, E., Parisio, C., Branca, J. J. V., Segnani, C., Ippolito, C., Pellegrini, C., Antonioli, L., Fornai, M., Micheli, L., Pacini, A., et al. (2020) · Cells · doi:10.3390/cells9081772 · Cited by 45 · see citing works
“Histamine and other mediators produced by MCs were found to be increased in the guts of patients affected by IBS, where they play a key role in visceral sensitivity [59], owing to their ability to directly enhance neuron excitability [53,54,60,61].”
Probiotics in Irritable Bowel Syndrome: A Review of Their Therapeutic Role
Kumar, L. S., Pugalenthi, L. S., Ahmad, M., Reddy, S., Barkhane, Z., & Elmadi, J. (2022) · Cureus · doi:10.7759/cureus.24240 · Cited by 52 · see citing works
“, histamine H1 receptor agonist (ebastine) reduced overall IBS symptoms, abdominal pain, and visceral hypersensitivity [41].”
BackgroundGwee, K., Lee, Y. Y., Suzuki, H., Ghoshal, U. C., Holtmann, G., Bai, T., Barbara, G., Chen, M., Chua, A. S. B., Gibson, P. R., et al. (2022) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.16046 · Cited by 45 · see citing works
Ion channels, ion channel receptors, and visceral hypersensitivity in irritable bowel syndrome
Fuentes, I. M., & Christianson, J. A. (2016) · Neurogastroenterology & Motility · doi:10.1111/nmo.12979 · Cited by 44 · see citing works
The Role of Diet in the Treatment of Irritable Bowel Syndrome
Singh, R., Salem, A., Nanavati, J., & Mullin, G. E. (2018) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2017.10.003 · Cited by 42 · see citing works
Intestinal Permeability in Disorders of Gut–Brain Interaction: From Bench to Bedside
Grover, M., Vanuytsel, T., & Chang, L. (2024) · Gastroenterology · doi:10.1053/j.gastro.2024.08.033 · Cited by 43 · see citing works
Neural control of gut homeostasis
Abdullah, N., Defaye, M., & Altier, C. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00293.2020 · Cited by 42 · see citing works
Decraecker, L., Looze, D. D., Hirsch, D., Schepper, H. D. D., Arts, J., Caenepeel, P., Bredenoord, A., Kolkman, J., Bellens, K., Beek, K. V., et al. (2024) · Gut · doi:10.1136/gutjnl-2023-331634 · Cited by 39 · see citing works
Self-citationMultiple chemical sensitivity: It's time to catch up to the science
Molot, J., Sears, M., & Anisman, H. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105227 · Cited by 40 · see citing works
- Authors
- Wouters, M. M., Balemans, D., Van Wanrooy, S., Dooley, J., Cibert-Goton, V., Alpizar, Y. A., Valdez-Morales, E. E., Nasser, Y., Van Veldhoven, P. P., Vanbrabant, W., Van der Merwe, S., Mols, R., Ghesquière, B., Cirillo, C., Kortekaas, I., Carmeliet, P., Peetermans, W. E., Vermeire, S., Rutgeerts, P., Augustijns, P., Hellings, P. W., Belmans, A., Vanner, S., Bulmer, D. C., Talavera, K., Vanden Berghe, P., Liston, A., & Boeckxstaens, G. E.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- VIB-KU Leuven Center for Microbiology (BE)
- KU Leuven (BE)
- Queen's University (CA)
- Amsterdam UMC Location University of Amsterdam (NL)
- Queen Mary University of London (GB)
- Corresponding author
- Boeckxstaens, Guy E.
- ORCID
- Wouters, Mira M.
- Dooley, James
- Alpizar, Yeranddy A.
- Nasser, Yasmin
- Mols, Raf
- Ghesquière, Bart
- Cirillo, Carla
- Kortekaas, Inge
- Carmeliet, Peter
- Peetermans, Willy E.
- Vermeire, Séverine
- Augustijns, Patrick
- Hellings, Peter W.
- Belmans, Ann
- Vanner, Stephen
- Bulmer, David C.
- Talavera, Karel
- Liston, Adrian
- Boeckxstaens, Guy E.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 150
- Issue
- 4
- Pages
- 875-887.e9
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2203163745
- Cited by
- 372
- References
- 46
- Citations by year
- 2026: 22 · 2025: 33 · 2024: 42 · 2023: 39 · 2022: 32 · 2021: 49 · 2020: 39 · 2019: 24 · 2018: 38 · 2017: 37 · 2016: 15 · 2014: 1
- FWCI
- 41.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Lirias (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Bowel and Cancer Research (1119105)
- Canadian Association of Gastroenterology
- KU Leuven (GOA 14.011)
- Crohn's and Colitis Canada
- Vlaamse regering
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- irritable bowel syndrome, TRPV1, visceral hypersensitivity, ebastine, mepyramine, capsaicin, submucosal neurons, dorsal root ganglion neurons, rectal distension, abdominal pain, histamine sensitization, health-related quality of life, gastrointestinal symptoms, barostat, calcium imaging
- MeSH terms
- Adolescent, Adult, Aged, Analgesics, Belgium, Biopsy, Butyrophenones, Double-Blind Method, Female, Gastrointestinal Agents, Histamine H1 Antagonists, Humans, Male, Middle Aged, Neurons, Pain Measurement, Piperidines, Quality of Life, Surveys and Questionnaires, Receptors, Histamine H1, Rectum, Remission Induction, Time Factors, Abdominal Pain, Treatment Outcome, Pain Threshold, Calcium Signaling, Receptor Cross-Talk, Irritable Bowel Syndrome, TRPV Cation Channels, Young Adult
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.
What counts as a claim ›How we measure confidence ›How we check this ›
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