Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain and bloating in association with altered bowel movements. Its pathogenesis and the underlying molecular mechanisms of visceral hyperalgesia remain elusive. Recent studies of somatic and other visceral pain models suggest a role for purinergic signaling mediated by the P2X receptor (P2XR) family.
Aims: To examine the role for P2XR signaling in the pathogenesis in a rat model of IBS-like visceral hyperalgesia.
Results: Visceral hypersensitivity was induced by colonic injection of 0.5% acetic acid (AA) in 10 day old rats and experiments were conducted at 8 weeks of age. Dorsal root ganglion (DRG) neurons innervating the colon were labeled by injection of DiI fluorescence into the colon wall. Visceral hypersensitivity was reversed by TNP-ATP, a potent P2X1, P2X3 and P2X2/3 receptor antagonist. Rapid application of ATP (20 µM) induced a fast inactivating current in colon specific DRG neurons from both control and AA-treated rats. There was a 2-fold-increase in the peak ATP responses in neurons from AA-treated rats. These currents were sensitive to TNP-ATP (100 nM). Under current-clamped conditions, ATP evoked a larger membrane depolarization in neurons from neonatal AA-treated rats than in controls. P2X3 receptor protein expression was significantly enhanced in colon specific DRGs 8 weeks after neonatal AA treatment.
Conclusions: These data suggest that the large enhancement of P2XR expression and function may contribute to the maintenance of visceral hypersensitivity, thus identifying a specific neurobiological target for the treatment of chronic visceral hyperalgesia.
- Acetic Acid
- Chronic Visceral Pain
- Dorsal Root Ganglion
- Irritable Bowel Syndrome
- P2X Receptor
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