{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:03:58Z","timestamp":1792065838421,"version":"4.4.0"},"reference-count":86,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,3,30]],"date-time":"2019-03-30T00:00:00Z","timestamp":1553904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Higher Education Institutional Excellence Program of the Ministry of Human Capacities in Hungary","award":["20765-3\/2018\/FEKUTSRTAT"],"award-info":[{"award-number":["20765-3\/2018\/FEKUTSRTAT"]}]},{"name":"PEPSYS: Complexity of Peptidergic Signalization and its Role in Systemic Diseases","award":["GINOP-2.3.2-15-2016-00050"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00050"]}]},{"name":"Human Resource Development Operational Program","award":["EFOP-3.6.2-16-2017-00006 LIVE LONGER"],"award-info":[{"award-number":["EFOP-3.6.2-16-2017-00006 LIVE LONGER"]}]},{"name":"Economic Development and Innovation Operational Program","award":["GINOP-2.3.2-15-2016-00048 STAY ALIVE"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00048 STAY ALIVE"]}]},{"name":"New National Excellence Program of the Ministry of Human Capacities","award":["\u00daNKP-18-3-IV-PTE-143"],"award-info":[{"award-number":["\u00daNKP-18-3-IV-PTE-143"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Inflammatory bowel diseases (IBD) have long been recognized to be accompanied by pain resulting in high morbidity. Transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) ion channels located predominantly on the capsaicin-sensitive sensory neurons play a complex role in hyperalgesia and neurogenic inflammation. This review provides an overview of their expression and role in intestinal inflammation, in particular colitis, that appears to be virtually inconsistent based on the thorough investigations of the last twenty years. However, preclinical results with pharmacological interventions, as well as scarcely available human studies, more convincingly point out the potential therapeutic value of TRPV1 and TRPA1 antagonists in colitis and visceral hypersensitivity providing future therapeutical perspectives through a complex, unique mechanism of action for drug development in IBD.<\/jats:p>","DOI":"10.3390\/ph12020048","type":"journal-article","created":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T03:21:26Z","timestamp":1554175286000},"page":"48","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Role of TRPV1 and TRPA1 Ion Channels in Inflammatory Bowel Diseases: Potential Therapeutic Targets?"],"prefix":"10.3390","volume":"12","author":[{"given":"Kata","family":"Csek\u0151","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School and Molecular Pharmacology Research Group, Szent\u00e1gothai Research Centre, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9532-2576","authenticated-orcid":false,"given":"Bram","family":"Beckers","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center (MUMC+), 6202 AZ Maastricht, The Netherlands"},{"name":"NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6202 AZ Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9856-9980","authenticated-orcid":false,"given":"Daniel","family":"Keszthelyi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center (MUMC+), 6202 AZ Maastricht, The Netherlands"},{"name":"NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6202 AZ Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Helyes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School and Molecular Pharmacology Research Group, Szent\u00e1gothai Research Centre, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"PharmInVivo Ltd., H-7629 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1016\/S0140-6736(16)31711-1","article-title":"Crohn\u2019s Disease","volume":"389","author":"Torres","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1016\/S0140-6736(16)32126-2","article-title":"Ulcerative Colitis","volume":"389","author":"Ungaro","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e0193202","DOI":"10.1371\/journal.pone.0193202","article-title":"Increased Fecal Calprotectin Levels in Crohn\u2019s Disease Correlate with Elevated Serum Th1- and Th17-Associated Cytokines","volume":"13","author":"Bourgonje","year":"2018","journal-title":"PLoS ONE"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/bja\/87.1.3","article-title":"Mechanisms of Inflammatory Pain","volume":"87","author":"Kidd","year":"2001","journal-title":"Br. J. Anaesth."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ibd.20848","article-title":"Pain and Inflammatory Bowel Disease","volume":"15","author":"Bielefeldt","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1111\/apt.14294","article-title":"Review Article: Transient Receptor Potential Channels as Possible Therapeutic Targets in Irritable Bowel Syndrome","volume":"46","author":"Beckers","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S0002-9270(01)04037-0","article-title":"Quality of Life in Inflammatory Bowel Disease in Remission: The Impact of IBS-Like Symptoms and Associated Psychological Factors","volume":"97","author":"Simren","year":"2002","journal-title":"Am. J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1136\/gut.19.1.64","article-title":"Sensibility of the Rectum to Distension and the Anorectal Distension Reflex in Ulcerative Colitis","volume":"19","author":"Farthing","year":"1978","journal-title":"Gut"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1016\/0016-5085(87)90255-1","article-title":"Anorectal Sensitivity and Responses to Rectal Distention in Patients with Ulcerative Colitis","volume":"93","author":"Rao","year":"1987","journal-title":"Gastroenterology"},{"key":"ref_10","first-page":"892","article-title":"Anorectal Manometry in Active and Quiescent Ulcerative Colitis","volume":"84","author":"Metcalf","year":"1989","journal-title":"Am. J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"981","DOI":"10.3109\/00365521.2011.579156","article-title":"Symptoms in Patients with Ulcerative Colitis in Remission Are Associated with Visceral Hypersensitivity and Mast Cell Activity","volume":"46","author":"Thijssen","year":"2011","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/apt.12409","article-title":"Letter: The Role of Sub-Clinical Inflammation and TRPV1 in the in Ulcerative Colitis in Remission","volume":"38","author":"Keszthelyi","year":"2013","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0304-3959(96)03062-X","article-title":"Rectal Afferent Function in Patients with Inflammatory and Functional Intestinal Disorders","volume":"66","author":"Bernstein","year":"1996","journal-title":"Pain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1136\/gut.47.4.497","article-title":"Perceptual Responses in Patients with Inflammatory and Functional Bowel Disease","volume":"47","author":"Chang","year":"2000","journal-title":"Gut"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1023\/A:1018885028501","article-title":"Standardization of Barostat Procedures for Testing Smooth Muscle Tone and Sensory Thresholds in the Gastrointestinal Tract","volume":"42","author":"Whitehead","year":"1997","journal-title":"Dig. Dis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.ceca.2005.06.028","article-title":"TRP Channels: An Overview","volume":"38","author":"Pedersen","year":"2005","journal-title":"Cell Calcium"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Liedtke, W.B., and Heller, S. (2007). The TRPC Family of Ion Channels: Relation to the TRP Superfamily and Role in Receptor- and Store-Operated Calcium Entry. TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades, CRC Press. Chapter 1.","DOI":"10.1201\/9781420005844"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1017\/S0033583509990072","article-title":"Structure-Functional Intimacies of Transient Receptor Potential Channels","volume":"42","author":"Latorre","year":"2009","journal-title":"Q. Rev. Biophys."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/j.1476-5381.2012.01851.x","article-title":"The Functions of TRPA1 and TRPV1: Moving Away from Sensory Nerves","volume":"166","author":"Fernandes","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.pain.2007.06.005","article-title":"Homologous and Heterologous Desensitization of Capsaicin and Mustard Oil Responses Utilize Different Cellular Pathways in Nociceptors","volume":"135","author":"Ruparel","year":"2008","journal-title":"Pain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S0092-8674(03)00158-2","article-title":"ANKTM1, a TRP-like Channel Expressed in Nociceptive Neurons, Is Activated by Cold Temperatures","volume":"112","author":"Story","year":"2003","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4300","DOI":"10.1523\/JNEUROSCI.5679-03.2004","article-title":"Protease-Activated Receptor 2 Sensitizes the Capsaicin Receptor Transient Receptor Potential Vanilloid Receptor 1 to Induce Hyperalgesia","volume":"24","author":"Amadesi","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1053\/j.gastro.2011.07.035","article-title":"Cathepsin S Is Activated During Colitis and Causes Visceral Hyperalgesia by a PAR2-Dependent Mechanism in Mice","volume":"141","author":"Cattaruzza","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10150","DOI":"10.1073\/pnas.152002699","article-title":"Bradykinin-12-Lipoxygenase-VR1 Signaling Pathway for Inflammatory Hyperalgesia","volume":"99","author":"Shin","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4211","DOI":"10.1038\/sj.emboj.7600893","article-title":"NGF Rapidly Increases Membrane Expression of TRPV1 Heat-Gated Ion Channels","volume":"24","author":"Zhang","year":"2005","journal-title":"EMBO J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4536","DOI":"10.1073\/pnas.0406030102","article-title":"A Proinflammatory Chemokine, CCL3, Sensitizes the Heat- and Capsaicin-Gated Ion Channel TRPV1","volume":"102","author":"Zhang","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","first-page":"1","article-title":"Sensitization of TRPV1 by EP 1 and IP Reveals Peripheral Nociceptive Mechanism of Prostaglandins","volume":"13","author":"Moriyama","year":"2005","journal-title":"Mol. Pain"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1016\/j.cellsig.2013.07.022","article-title":"Regulation of Inflammation by Extracellular Acidification and Proton-Sensing GPCRs","volume":"25","author":"Okajima","year":"2013","journal-title":"Cell. Signal."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.jpain.2006.12.004","article-title":"Potentiation of Nociceptive Responses to Low PH Injections in Humans by Prostaglandin E2","volume":"8","author":"Rukwied","year":"2019","journal-title":"J. Pain"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10974","DOI":"10.1523\/JNEUROSCI.2619-04.2004","article-title":"Acid-Induced Pain and Its Modulation in Humans","volume":"24","author":"Jones","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1016\/S0140-6736(00)04503-7","article-title":"Vanilloid Receptor 1 Immunoreactivity in Inflamed Human Bowel","volume":"357","author":"Yiangou","year":"2001","journal-title":"Lancet"},{"key":"ref_32","first-page":"11335","article-title":"Upregulation of the Transient Receptor Potential Vanilloid 1 in Colonic Epithelium of Patients with Active Inflammatory Bowel Disease","volume":"10","author":"Luo","year":"2017","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kun, J., Szitter, I., Kem\u00e9ny, \u00c1., Perkecz, A., Kereskai, L., Poh\u00f3czky, K., Vincze, \u00c1., Szab\u00f3, I., Szolcs\u00e1nyi, J., Pint\u00e9r, E., and Helyes, Z. (2014). Upregulation of the Transient Receptor Potential Ankyrin 1 Ion Channel in the Inflamed Human and Mouse Colon and Its Protective Roles. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108164"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Rizopoulos, T., Papadaki-Petrou, H., and Assimakopoulou, M. (2018). Expression Profiling of the Transient Receptor Potential Vanilloid (TRPV) Channels 1, 2, 3 and 4 in Mucosal Epithelium of Human Ulcerative Colitis. Cells, 7.","DOI":"10.3390\/cells7060061"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1136\/gut.2009.194449","article-title":"Expression of the TRPV1 Receptor Differs in Quiescent Inflammatory Bowel Disease with or without Abdominal Pain","volume":"59","author":"Akbar","year":"2010","journal-title":"Gut"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1002\/j.1532-2149.2013.00309.x","article-title":"Alterations in Mucosal Neuropeptides in Patients with Irritable Bowel Syndrome and Ulcerative Colitis in Remission: A Role in Pain Symptom Generation?","volume":"17","author":"Keszthelyi","year":"2013","journal-title":"Eur. J. Pain"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1136\/gutjnl-2015-310710","article-title":"The TRPA1 Ion Channel Is Expressed in CD4+ T Cells and Restrains T Cell-Mediated Colitis through Inhibition of TRPV1","volume":"66","author":"Bertin","year":"2017","journal-title":"Gut"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4036","DOI":"10.3748\/wjg.v24.i35.4036","article-title":"Daikenchuto (Da-Jian-Zhong-Tang) Ameliorates Intestinal Fibrosis by Activating Myofibroblast Transient Receptor Potential Ankyrin 1 Channel","volume":"24","author":"Hiraishi","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.jcmgh.2017.12.005","article-title":"Activation of Myofibroblast TRPA1 by Steroids and Pirfenidone Ameliorates Fibrosis in Experimental Crohn\u2019s Disease","volume":"5","author":"Kurahara","year":"2018","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.ejphar.2015.03.017","article-title":"Experimental Colitis Models: Insights into the Pathogenesis of in Fl Ammatory Bowel Disease and Translational Issues","volume":"759","author":"Valatas","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_41","first-page":"1341","article-title":"Animal Models of Ulcerative Colitis and Their Application in Drug Research","volume":"7","author":"Low","year":"2013","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Perse, M., and Cerar, A. (2012). Dextran Sodium Sulphate Colitis Mouse Model: Traps and Tricks. J. Biomed. Biotechnol., 718617.","DOI":"10.1155\/2012\/718617"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5581","DOI":"10.3748\/wjg.v13.i42.5581","article-title":"Insights from Advances in Research of Chemically Induced Experimental Models of Human Inflammatory Bowel Disease","volume":"13","author":"Kawada","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1084\/jem.187.3.389","article-title":"Interleukin 7 Transgenic Mice Develop Chronic Colitis with Decreased Interleukin 7 Protein Accumulation in the Colonic Mucosa","volume":"187","author":"Watanabe","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/0092-8674(93)80069-Q","article-title":"Spontaneous Development of Inflammatory Bowel Disease in T Cell Receptor Mutant Mice","volume":"75","author":"Mombaerts","year":"1993","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1053\/j.gastro.2007.07.010","article-title":"Lymphocyte-Dependent and Th2 Cytokine-Associated Colitis in Mice Deficient in Wiskott-Aldrich Syndrome Protein","volume":"133","author":"Nguyen","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5733","DOI":"10.4049\/jimmunol.161.10.5733","article-title":"A Novel Model of Inflammatory Bowel Disease: Mice Deficient for the Multiple Drug Resistance Gene, Mdr1a, Spontaneously Develop Colitis","volume":"161","author":"Panwala","year":"1998","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0092-8674(93)80067-O","article-title":"Ulcerative Colitis-like Disease in Mice with a Disrupted Interleukin-2 Gene","volume":"75","author":"Sadlack","year":"1993","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/ng0695-143","article-title":"Ulcerative Colitis and Adenocarcinoma of the Colon in G\u03b1i2-Deficient Mice","volume":"10","author":"Rudolph","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1152\/ajpgi.90578.2008","article-title":"Localization of TRPV1 and Contractile Effect of Capsaicin in Mouse Large Intestine: High Abundance and Sensitivity in Rectum and Distal Colon","volume":"297","author":"Matsumoto","year":"2009","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1007\/s00535-011-0495-6","article-title":"The Proximodistal Aggravation of Colitis Depends on Substance P Released from TRPV1-Expressing Sensory Neurons","volume":"47","author":"Engel","year":"2012","journal-title":"J. Gastroenterol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0304-3940(01)02480-6","article-title":"Vanilloid Receptor Type 1-Immunoreactivity Is Expressed by Intrinsic Afferent Neurones in the Guinea-Pig Myenteric Plexus","volume":"319","author":"Mckay","year":"2002","journal-title":"Neurosci. Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1053\/j.gastro.2011.04.049","article-title":"Transient Receptor Potential Ankyrin 1 Is Expressed by Inhibitory Motoneurons of the Mouse Intestine","volume":"141","author":"Poole","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1152\/ajpgi.00289.2011","article-title":"Activation of TRPA1 by Luminal Stimuli Induces EP 4-Mediated Anion Secretion in Human and Rat Colon","volume":"302","author":"Kaji","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/ni.3009","article-title":"The Ion Channel TRPV1 Regulates the Activation and Proinflammatory Properties of CD4+ T Cells","volume":"15","author":"Bertin","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1136\/gut.52.5.713","article-title":"Vanilloid Receptor-1 Containing Primary Sensory Neurones Mediate Dextran Sulphate Sodium Induced Colitis in Rats","volume":"52","author":"Kihara","year":"2003","journal-title":"Gut"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1111\/j.1365-2982.2004.00549.x","article-title":"Vanilloid Receptor 1 Antagonists Attenuate Disease Severity in Dextran Sulphate Sodium-Induced Colitis in Mice","volume":"16","author":"Kimball","year":"2004","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.gassur.2004.07.011","article-title":"Inhibition of the Vanilloid Receptor Subtype-1 Attenuates TNBS-Colitis","volume":"7","author":"Fujino","year":"2004","journal-title":"J. Gastrointest. Surg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.ejphar.2012.10.014","article-title":"Role of TRPV1 and TRPA1 in Visceral Hypersensitivity to Colorectal Distension during Experimental Colitis in Rats","volume":"698","author":"Vermeulen","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0014-2999(93)90431-G","article-title":"Topical Capsaicin Administration Protects against Trinitrobenzene Sulfonic Acid-Induced Colitis in the Rat","volume":"249","author":"Goso","year":"1993","journal-title":"Eur. J. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/j.1365-2982.2007.00928.x","article-title":"A Potential Role for the Vanilloid Receptor TRPV1 in the Therapeutic Effect of Curcumin in Dinitrobenzene Sulphonic Acid-Induced Colitis in Mice","volume":"19","author":"Martelli","year":"2007","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1744806917726416","DOI":"10.1177\/1744806917726416","article-title":"Oral Administration of Curcumin Attenuates Visceral Hyperalgesia through Inhibiting Phosphorylation of TRPV1 in Rat Model of Ulcerative Colitis","volume":"13","author":"Yang","year":"2017","journal-title":"Mol. Pain"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1007\/s12031-010-9366-5","article-title":"The Role of Transient Receptor Potential Vanilloid 1 (Trpv1) Receptors in Dextran Sulfate-Induced Colitis in Mice","volume":"42","author":"Szitter","year":"2010","journal-title":"J. Mol. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jphs.2017.12.012","article-title":"Transient Receptor Potential Vanilloid 1 and Transient Receptor Potential Ankyrin 1 Contribute to the Progression of Colonic Inflammation in Dextran Sulfate Sodium-Induced Colitis in Mice: Links to Calcitonin Gene-Related Peptide and Substance P","volume":"136","author":"Utsumi","year":"2018","journal-title":"J. Pharmacol. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s00109-005-0016-2","article-title":"Vanilloid Receptor (TRPV1)-Deficient Mice Show Increased Susceptibility to Dinitrobenzene Sulfonic Acid Induced Colitis","volume":"84","author":"Massa","year":"2006","journal-title":"J. Mol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1053\/j.gastro.2011.07.002","article-title":"TRPA1 and Substance P Mediate Colitis in Mice","volume":"141","author":"Engel","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1152\/ajpgi.00421.2014","article-title":"TRPV1 Sensitization Mediates Postinflammatory Visceral Pain Following Acute Colitis","volume":"309","author":"Lapointe","year":"2015","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.autneu.2011.07.008","article-title":"TRPV1 Expressing Extrinsic Primary Sensory Neurons Play a Protective Role in Mouse Oxazolone-Induced Colitis","volume":"166","author":"Lee","year":"2012","journal-title":"Auton. Neurosci. Basic Clin."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00011-014-0712-x","article-title":"Role of Neurokinin 1 Receptors in Dextran Sulfate-Induced Colitis: Studies with Gene-Deleted Mice and the Selective Receptor Antagonist Netupitant","volume":"63","author":"Szitter","year":"2014","journal-title":"Inflamm. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.fitote.2017.09.007","article-title":"Effects of Curcumin and Curcumin Analogues on TRP Channels","volume":"122","author":"Nalli","year":"2017","journal-title":"Fitoterapia"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.neulet.2011.07.054","article-title":"Crucumin ((E,E)-1,7-Bis(4-Hydroxy-3-Methoxyphenyl)-1,6-Heptadiene-3,5-Dione) Activates and Desensitizes the Nociceptor Ion Channel TRPA1","volume":"503","author":"Leamy","year":"2011","journal-title":"Neurosci. Lett."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/ibd.21391","article-title":"Modulation of Neutrophil Motility by Curcumin: Implications for Inflammatory Bowel Disease","volume":"17","author":"Larmonier","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/nmo.12145","article-title":"Curcumin Acts via Transient Receptor Potential Vanilloid-1 Receptors to Inhibit Gut Nociception and Reverses Visceral Hyperalgesia","volume":"25","author":"Zhi","year":"2013","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/j.cgh.2006.08.008","article-title":"Curcumin Maintenance Therapy for Ulcerative Colitis: Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial","volume":"4","author":"Hanai","year":"2006","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1096\/fj.05-4943fje","article-title":"Up-Regulation of Anandamide Levels as an Endogenous Mechanism and a Pharmacological Strategy to Limit Colon Inflammation","volume":"20","author":"Valenti","year":"2006","journal-title":"FASEB J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1111\/nmo.12931","article-title":"The Gastrointestinal Tract\u2014A Central Organ of Cannabinoid Signaling in Health and Disease","volume":"28","author":"Hasenoehrl","year":"2016","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1042\/CS20171288","article-title":"Cannabidiol and Palmitoylethanolamide Are Anti-Inflammatory in the Acutely Inflamed Human Colon","volume":"131","author":"Couch","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1111\/bph.13084","article-title":"The Anti-Inflammatory Mediator Palmitoylethanolamide Enhances the Levels of 2-Arachidonoyl-Glycerol and Potentiates Its Actions at TRPV1 Cation Channels","volume":"173","author":"Petrosino","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_79","first-page":"698","article-title":"Protective Role of Palmitoylethanolamide in Contact Allergic Dermatitis","volume":"65","author":"Petrosino","year":"2010","journal-title":"Exp. Allergy Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1021\/jm0495071","article-title":"Identification and Biological Evaluation of 4-(3-Trifluoromethylpyridin-2-Yl)Piperazine-1-Carboxylic Acid (5-Trifluoromethylpyridin-2-Yl) Amide, a High Affinity TRPV1 (VR1) Vanilloid Receptor Antagonist","volume":"48","author":"Swanson","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"7459","DOI":"10.1523\/JNEUROSCI.1483-07.2007","article-title":"Nonthermal Activation of Transient Receptor Potential Vanilloid-1 Channels in Abdominal Viscera Tonically Inhibits Autonomic Cold-Defense Effectors","volume":"27","author":"Steiner","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1097\/j.pain.0000000000000610","article-title":"A Randomized, Double-Blind, Positive-Controlled, 3-Way Cross-over Human Experimental Pain Study of a Trpv1 Antagonist (V116517) in Healthy Volunteers and Comparison with Preclinical Profile","volume":"157","author":"Harris","year":"2016","journal-title":"Pain"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.pain.2008.01.024","article-title":"Pharmacological Blockade of the Vanilloid Receptor TRPV1 Elicits Marked Hyperthermia in Humans","volume":"136","author":"Gavva","year":"2008","journal-title":"Pain"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s00210-015-1088-3","article-title":"TRPA1 as a Drug Target\u2014Promise and Challenges","volume":"388","author":"Chen","year":"2015","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.1016\/j.jpain.2016.01.397","article-title":"NEO6860, a Novel Modality Selective TRPV1 Antagonist: Results from a Phase I, Double-Blind, Placebo-Controlled Study in Healthy Subjects","volume":"17","author":"Chiche","year":"2016","journal-title":"J. Pain"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1111\/bph.12414","article-title":"Transient Receptor Potential (TRP) Channels: A Clinical Perspective","volume":"171","author":"Kaneko","year":"2013","journal-title":"Br. J. Pharmacol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/12\/2\/48\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:41:46Z","timestamp":1760186506000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/12\/2\/48"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,30]]},"references-count":86,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["ph12020048"],"URL":"https:\/\/doi.org\/10.3390\/ph12020048","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,30]]}}}