Fig. 8.

Antihyperalgesic and antinflammatory effect of ipl and s.c. injection of the PKR1-preferring antagonist PC1 in mice and rats. (A and B) In mice ipl injection of PC1 24 h after CFA reverted the thermal hyperalgesia (0.01, 0.05, and 0.2 μg) for 1–3 h (A) and abolished the CFA-induced reduction in the body weight-bearing of the inflamed paw (0.05 μg) for ≈1 h (B). (C) In rats, PC1 (0.01 μg, ipl) reverted CFA-induced mechanical hyperalgesia for ≈2 h. (D) In rats, PC1 dose-dependently antagonized the CFA-induced hyperalgesia also by systemic injections (20–150 μg/kg, s.c.), bringing the nociceptive threshold of inflamed paw toward that of contralateral noninflamed paw. (E) In rats, repeated administration of PC1 (150 μg/kg, s.c.), at 6 and 24 h after CFA injection, accelerated recovery of inflamed paw to normal paw volume and significantly reduced the inflammation-induced PK2 up-regulation (Inset). In rats, i.p. injection of oyster glycogen induced marked extravasation of granulocytes into peritoneal cavity and decreased the nociceptive threshold evaluated with the paw-pressure test. PC1 (150 μg/kg, s.c.) abolished the systemic hyperalgesia caused by GrPK2, released into circulation. (F) Intraperitoneal injection of saline did not modify the mechanical nociceptive threshold (CO).