PAR4 plays an endogenous antinociceptive role in inflammatory but not in stress-induced colorectal hyperalgesia in mice

Activation of proteinase-activated receptor-4 (PAR4) from the colonic lumen by its agonist (PAR4-AP) or cathepsin-G (Cat-G) has antinociceptive effect to colorectal distension (CRD) in mice in basal conditions. Aims: To clarify if PAR4 activation has antihyperalgesic effect in 2 visceral hypersensitivity models, water avoidance stress (WAS) and TNBS colitis, and to test if endogenous PAR4 activation is present in these conditions. Methods: In one group of C57/BL6 mice, animals underwent WAS. A second group was treated with TNBS (20mg/kg intracolonically/ic/). Controls were either SHAM-stressed or received saline…