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Area of Science:

  • Gastroenterology
  • Pain Research
  • Pharmacology

Background:

  • Serine proteases are implicated as mediators of visceral pain.
  • Post-inflammatory irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity.

Purpose of the Study:

  • To investigate the role of serine proteases in visceral pain using novel serine protease inhibitors.
  • To evaluate the efficacy of serine protease inhibitors in a rat model of post-inflammatory IBS.

Main Methods:

  • Colitis was induced in rats using trinitrobenzenesulphonic acid.
  • Visceral hypersensitivity was assessed via visceromotor responses (VMRs) to colorectal distension.
  • Rats were treated with serine protease inhibitors (nafamostat, UAMC-00050, UAMC-01162) and molecular targets were quantified.

Main Results:

  • Elevated VMRs in post-colitis rats were significantly reduced by serine protease inhibitors in a dose-dependent manner.
  • Increased expression of serine proteases (tryptase-αβ-1), protease-activated receptors (PAR4), and trypsin-like activity were observed in the colon.
  • PAR2 and TRPA1 expression co-localized with sensory nerve fibers.

Conclusions:

  • Increased serine protease activity and expression contribute to post-inflammatory visceral hypersensitivity.
  • Serine protease inhibitors show promise as a therapeutic strategy for IBS-related visceral pain.