Negus S S, Butelman E R, Gatch M B, Woods J H
Department of Pharmacology, University of Michigan, Ann Arbor, USA.
J Pharmacol Exp Ther. 1995 Aug;274(2):805-14.
When administered s.c. in the tail, both prostaglandin E2 (PGE2; 1.58-158.0 micrograms) and bradykinin (BK; 0.01-1.0 microgram) produced a dose-dependent allodynia in a warm-water tail-withdrawal assay in rhesus monkeys. PGE2 (A50 = 5.3 +/- 0.15 microgram) was 143-fold less potent than BK (A50 = 0.037 +/- 0.012 microgram) in producing allodynia at 42 degrees C. However, PGE2 (15.8 micrograms) was longer acting than an equieffective dose of BK (0.1 microgram), and the highest dose of PGE2 (158.0 micrograms) was the only treatment to produce allodynia when 38 degrees 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 microgram) and PGE2 (15.8 micrograms), 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.
当在恒河猴尾巴处皮下注射时，前列腺素E2（PGE2；1.58 - 158.0微克）和缓激肽（BK；0.01 - 1.0微克）在温水尾巴撤离试验中均产生剂量依赖性痛觉过敏。在42℃产生痛觉过敏方面，PGE2（半数有效量[A50] = 5.3 ± 0.15微克）的效力比BK（A50 = 0.037 ± 0.012微克）低143倍。然而，PGE2（15.8微克）的作用时间比等效剂量的BK（0.1微克）更长，并且当使用38℃水作为热刺激时，最高剂量的PGE2（158.0微克）是唯一产生痛觉过敏的处理方式，这表明PGE2是比BK更有效的痛觉过敏诱导剂。皮下注射于背部的吗啡（0.1 - 3.2毫克/千克）完全阻断了BK（0.1微克）和PGE2（15.8微克）的痛觉过敏作用，尽管吗啡对BK（A50 = 0.26 ± 0.085毫克/千克）的效力比对PGE2（A50 = 0.65 ± 0.14毫克/千克）强两倍多。吗啡的作用被阿片类拮抗剂夸达佐辛（0.1毫克/千克）拮抗，表明吗啡的作用是由阿片受体介导的。皮下注射于背部的非甾体抗炎药酮咯酸（0.32 - 10.0毫克/千克）完全阻断了BK的痛觉过敏作用（A50 = 0.60 ± 0.095毫克/千克），但未改变PGE2诱导的痛觉过敏。酮咯酸对BK的抗痛觉过敏作用未被夸达佐辛（1.0毫克/千克）拮抗，表明这些作用不是由μ或κ阿片受体介导的。此外，相对于吗啡，酮咯酸起效较慢且作用持续时间较长。这些发现表明，在此过程中BK的痛觉过敏作用完全由花生四烯酸代谢的环氧化酶产物如PGE2介导。
