Although a neurogenic mechanism involving NK-1 receptor activation has been demonstrated for PAR1 agonist-induced paw edema , there is currently no evidence that such a mechanism also occurs in the gut. Contrary to the situation with PAR2, subinflammatory doses of PAR1 agonists did not induce hyperalgesia after intraplantar injection, but they increased nociceptive threshold in rats and significantly inhibited inflammatory hyperalgesia induced by carrageenan . Here again, there is no evidence […]
Within 2 h after their intracolonic administration, PAR2 agonists (PAR2-activating peptides and trypsin) also caused nociceptor activation at a spinal level, as demonstrated by increased fos protein expression in the superficial laminae of the spinal dorsal horn . Subinflammatory doses of PAR2 agonists from the colonic lumen provoked a significant increase in the number of abdominal contractions in response to rectal distension, which is characteristic of visceral hyperalgesia . Here […]
This hypothesis is supported by the fact that PAR2 can be activated by proteinases from pathogens such as dust mites or Porphyromonas gingivalis . PAR2 activation by pathogens would support a proinflammatory role for PAR2 in enteric infections and would suggest that PAR2 antagonists might be helpful in the […]
These results showed that the intestinal inflammation induced by PAR2 agonists is under neural control, and is affected by the release of neuropeptides such as substance P and CGRP. The release of substance P and CGRP, as a direct result of activation of PAR2 on ENS neurons, was not demonstrated in this study. Evidence supporting this idea include the facts that functional PAR2 has been identified on ENS neurons that also expressed […]
Although the presence of PARj, PAR2 and PAR4 was not clearly established, a study by Gao et al suggested that those receptors act on neurons that regulate enteric motor function in the guinea pig small intestine.
This large expression of PARs strongly suggests that they play […]
The four PARs are expressed throughout the gastrointestinal tract in different cell types . For example, immunoreactive PARj and PAR2 have been detected in more than 60% of neurons from the myenteric plexus of the guinea pig small intestine, both in primary cultures and in whole mounts of myenteric tissues. A large proportion of neurons expressing substance P, a primary excitatory neuropeptide, also expressed PARj (89%) and PAR2 (50%). Similarly, […]
The ENS also influences vasodilation and vascular permeability indirectly, through the release of mast cell mediators . Because enteric neurons are closely associated with macrophages and lymphocytes in the gut wall, the release of VIP from those neurons seems to aggravate inflammation by stimulating cytokine […]
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