Proteinases and proteinase-activated receptor 2: a possible role to promote visceral hyperalgesia in rats.

Area of Science:

• Gastroenterology
• Neuroscience
• Pain Research

Background:

• Proteinase-activated receptor-2 (PAR-2) is highly expressed in the gastrointestinal tract.
• PAR-2 can be activated by proteases like trypsin and mast cell tryptase.
• Activation occurs via peptides mimicking the tethered ligand, such as SLIGRL-NH2 in rats.

Purpose of the Study:

• To investigate the effect of colonic PAR-2 agonist administration on visceral sensitivity to rectal distention in conscious rats.
• To determine if PAR-2 activation influences pain signaling in the colon.

Main Methods:

• Rats were equipped with electrodes to record abdominal contractions, a visceral pain indicator.
• Intracolonic infusion of PAR-2 agonists (SLIGRL-NH2) or trypsin was administered.
• Visceral sensitivity was assessed via rectal distention at various time points post-infusion.
• Spinal Fos expression, intestinal permeability, and inflammation markers were analyzed.

Main Results:

• Intracolonic SLIGRL-NH2 and trypsin significantly increased abdominal contractions at higher rectal distention volumes, 10-24 hours post-infusion.
• This PAR-2 agonist-induced hyperalgesia was mediated by NK1 receptors but not by indomethacin.
• SLIGRL-NH2 elevated spinal Fos expression and increased intestinal permeability without causing inflammation.

Conclusions:

• Sub-inflammatory doses of colonic PAR-2 agonists induce delayed rectal hyperalgesia in rats.
• This effect is linked to spinal afferent neuron activation, altered intestinal permeability, and NK1 receptor involvement.
• Proteinases and PAR-2 may play a role in the development of visceral hyperalgesia.