Effects of PAR-2 agonists on synovial perfusion and joint swelling. (a) Laser Doppler image showing vasodilatation 1 minute after topical administration of 1 μg of the PAR-2 agonist SLIGRL-NH₂ (SLIG) to PAR-2^+/+ mice. (b) ASKH95 (1 μg) administered to PAR-2^+/+ mice also elicits vasodilatation. (c) ASKH95 (1 μg) administered to PAR-2^–/– mice is without effect. (d) The control peptide ASKH115 (1 μg) administered to PAR-2^+/+ mice is without effect. (e) Histogram showing quantitative data for the vasodilator effect of SLIG in PAR-2^+/+ mice (+/+ SLIG), ASKH95 in both PAR-2^–/– mice (–/– 95) and wild-type mice (+/+ 95), and ASKH115 in wild-type mice (+/+ 115). Perfusion is measured in arbitrary “flux units” and color coded in the images, with dark blue being the lowest and dark red the highest. Data are presented as mean ± SEM. n = 5–7. *P < 0.01 compared with +/+ 95. (f) Intra-articular injection of 100 μg of SLIG in PAR-2^+/+ mice (filled squares) elicits an increase in joint diameter that reaches a maximum within 4 hours but declines thereafter. The synthetic PAR-2 agonist ASKH95 (100 μg) produces joint swelling that reaches maximum by 24 hours and is sustained thereafter in PAR-2^+/+ mice (filled circles), a response that differs significantly compared with the same dose of this peptide in PAR-2^–/– mice (open circles) and control peptide ASKH115 in wild-type mice (filled triangles). Data are presented as mean ± SEM; n = 4–10.