EFFECTS OF MORPHINE AND KETOROLAC ON THERMAL ALLODYNIA INDUCED BY PROSTAGLANDIN E(2) AND BRADYKININ IN RHESUS-MONKEYS

When administered s,c, in the tail, both prostaglandin E(2) (PGE(2); 1 .58-158.0 mu g) and bradykinin (BK; 0.01-1.0 mu g) produced a dose-dep endent allodynia in a warm-water tail-withdrawal assay in rhesus monke ys. PGE(2) (A(50) = 5.3 +/- 0.15 mu g) was 143-fold less potent than B K (A(50) = 0.037 +/- 0.012 mu g) in producing allodynia at 42 degrees C. However, PGE(2) (15.8 mu g) was longer acting than an equieffective dose of BK(0.1 mu g), and the highest dose of PGE(2) (158.0 mu g) was the only treatment to produce allodynia when 38 degrees C water was u sed as the thermal stimulus, suggesting that PGE(2) was a more efficac ious allodynic agent than BK. Morphine (0.1-3.2 mg/kg) administered s. c. in the back completely blocked the allodynic effects of both BK (0. 1 mu g) and PGE(2) (15.8 mu g), although morphine was more than twice as potent against BK (A(50) = 0.25 +/- 0.085 mg/kg) than against PGE(2 ) (A(50) = 0.65 +/- 0.14 mg/kg). The effects of morphine were antagoni zed by the opioid antagonist quadazocine (0.1 mg/kg), indicating that morphine's effects were mediated by opioid receptors. The nonsteroidal anti-inflammatory drug ketorolac (0.32-10.0 mg/kg) administered s.c. in the back completely blocked the allodynic effects of BK (A(50) = 0. 60 +/- 0.095 mg/kg) but did not alter allodynia induced by PGE,. The a ntiallodynic effects of ketorolac against BK were not antagonized by q uadazocine (1.0 mg/kg), indicating that these effects were not mediate d by mu or kappa opioid receptors. Furthermore, relative to morphine, ketorolac displayed a slower onset and a longer duration of action. Th ese findings suggest that the allodynic effects of SK in this procedur e were mediated entirely by cyclooxygenase products of arachidonic aci d metabolism, such as PGE(2).