[Abstract Title]. - Society for Neuroscience

269. Pain: Visceral Pain II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 269.8/GG23
Topic: D.08.n. Visceral pain
Support: NIH award NS 19912
Title: P2X3 receptor contribution to colon hypersensitivity in the mouse
Authors: *M. SHINODA, J. LA, K. BIELEFELDT, G. F. GEBHART;
Ctr. for Pain Res., Univ. Pittsburgh, Pittsburgh, PA
Abstract: Irritable bowel syndrome is a functional gastrointestinal disorder of unknown etiology
characterized by pain in the absence of colon inflammation. ATP is released during colon
distension and increases responses of colon afferent fibers to stretch. In the present experiments,
we examined the role of purinergic (P2X) receptors in colon hypersensitivity. Changes in
visceral nociceptive behavior as the visceromotor response to colon distension and ATP release
from colon by colon distension were measured after intracolonic treatment with zymosan (which
reproduces major features of IBS - persistent hypersensitivity without colon inflammation) or
saline. Intracolonic zymosan (3 mg in 100 κl daily for 3 days), but not saline, produced
significant colon hypersensitivity, which was significantly reduced in both P2X3 +/- and P2X3 -/-
mice relative to control (wildtype) mice. However, ATP release did not change after intracolonic
zymosan or saline in either wild type or P2X3 -/- mice. In whole cell patch clamp studies, resting
membrane potential, input resistance and rheobase were decreased in colon sensory neurons
from mice treated with zymosan compared to saline. Similarly, the A-type K + current was found
to be decreased, revealing increased excitability of colon sensory neurons associated with colon
hypersensitivity. Immunohistochemically, the number of P2X3 receptor-positive colon sensory
neurons was increased by intracolonic treatment with zymosan. These results suggest that P2X3
receptors may be important peripheral mediators of colon mechanosensation and development of
hypersensitivity in this model.
Disclosures: M. Shinoda, None; J. La, None; K. Bielefeldt, None; G.F. Gebhart, None.
Poster
269. Pain: Visceral Pain II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 269.9/GG24