Effects of morphine and ketorolac on thermal allodynia induced by prostaglandin E₂ and bradykinin in rhesus monkeys

When administered s.c. in the tail, both prostaglandin E₂ (PGE₂; 1.58- 158.0 μg) and bradykinin (BK; 0.01-1.0 μg) produced a dose-dependent allodynia in a warm-water tail-withdrawal assay in rhesus monkeys. PGE₂ (A₅₀ = 5.3 ± 0.15 μg) was 143-fold less potent than BK (A₅₀ = 0.037 ± 0.012 μg) in producing allodynia at 42°C. However, PGE₂ (15.8 μg) was longer acting than an equieffective dose of BK (0.1 μg), and the highest dose of PGE₂ (158.0 μg) was the only treatment to produce allodynia when 38°C water was used as the thermal stimulus, suggesting that PGE₂ was a more efficacious 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 μg) and PGE₂ (15.8 μg), although morphine was more than twice as potent against BK (A₅₀ = 0.26 ± 0.085 mg/kg) than against PGE₂ (A₅₀ = 0.65 + 0.14 mg/kg). The effects of morphine were antagonized 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 (A₅₀ = 0.60 ± 0.095 mg/kg) but did not alter allodynia induced by PGE₂. The antiallodynic effects of ketorolac against BK were not antagonized by quadazocine (1.0 mg/kg), indicating that these effects were not mediated by mu or kappa opioid receptors. Furthermore, relative to morphine, ketorolac displayed a slower onset and a longer duration of action. These findings suggest that the allodynic effects of BK in this procedure were mediated entirely by cyclooxygenase products of arachidonic acid metabolism, such as PGE₂.