title: Visceral hyperalgesia caused by peptide YY deletion and Y2 receptor antagonism.
abstract: Altered levels of colonic peptide YY (PYY) have been reported in patients suffering from functional and inflammatory bowel disorders. While the involvement of neuropeptide Y (NPY) and Y receptors in the regulation of nociception is well established, the physiological role of PYY in somatic and visceral pain is poorly understood. In this work, the role of PYY in pain sensitivity was evaluated using PYY knockout (PYY(-/-)) mice and Y2 receptor ligands. PYY(-/-)mice were more sensitive to somatic thermal pain compared to wild type (WT) mice. Visceral pain was assessed by evaluating pain-related behaviors, mouse grimace scale (MGS) and referred hyperalgesia after intrarectal administration of allyl isothiocyanate (AITC, 1 or 2%) or its vehicle, peanut oil. The pain-related behaviors induced by AITC were significantly exaggerated by PYY deletion, whereas the MGS readout and the referred hyperalgesia were not significantly affected. The Y2 receptor antagonist, BII0246, increased pain-related behaviors in response to intrarectal AITC compared to vehicle treatment while the Y2 receptor agonist, PYY(3-36), did not have a significant effect. These results indicate that endogenous PYY has a hypoalgesic effect on somatic thermal and visceral chemical pain. The effect on visceral pain seems to be mediated by peripheral Y2 receptors.
authors.affiliation: Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Hassan
authors.affiliation: Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
authors.forename: Piyush
authors.initials: P
authors.lastname: Jain
authors.affiliation: Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
authors.forename: Raphaela
authors.initials: R
authors.lastname: Mayerhofer
authors.affiliation: Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
authors.forename: Esther E
authors.initials: EE
authors.lastname: Fröhlich
authors.affiliation: Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
authors.forename: Aitak
authors.initials: A
authors.lastname: Farzi
authors.affiliation: Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Reichmann
authors.affiliation: Neurobiology Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.affiliation: Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Holzer
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000528:radiation effects*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology*; D017879:Isothiocyanates / Q000008:administration & dosage; D051379:Mice; D018345:Mice, Knockout; D019894:Peptide YY / Q000172:deficiency*; D011964:Receptors, Gastrointestinal Hormone / Q000037:antagonists & inhibitors*
chemical_list: D017879:Isothiocyanates; D011964:Receptors, Gastrointestinal Hormone; C082172:peptide YY receptor; D019894:Peptide YY; C004471:allyl isothiocyanate