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.
Highlights
The gut hormone peptide YY (PYY) is a member of the neuropeptide Y (NPY) family which includes pancreatic polypeptide
PYY knockout exaggerates pain-related behaviors induced by intrarectal allyl isothiocyanate (AITC)
We examined the effects of genetic PYY deletion and Y2 receptor ligands on somatic sensitivity to thermal and mechanical pain and visceral sensitivity to chemical pain
Summary
The gut hormone peptide YY (PYY) is a member of the neuropeptide Y (NPY) family which includes pancreatic polypeptide. Knockout of Y1 receptors is associated with thermal, chemical, and mechanical somatic hyperalgesia and exaggerated acetic acid- and MgSO4 -induced visceral pain[5,6]. NPY acting through Y1 receptors controls the production of several neuropeptides including substance P and calcitonin gene-related peptide (CGRP), which subserve pronociceptive functions in the CNS9. In addition to their effect on spinal pain pathways, Y receptor ligands affect visceral pain mediated by vagal afferent pathways, as c-Fos expression in the nucleus tractus solitarii (NTS) following intragastric acid challenge is enhanced in Y2 and Y4 receptor knockout mice[10]. Since PYY(3–36), the main circulatory form of PYY, has a preferential affinity to Y2 receptors[3], the effects of the Y2 receptor agonist, PYY(3–36), and the Y2 receptor antagonist, BIIE0246, on visceral pain sensitivity were evaluated
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call