内源性一氧化氮对小鼠吗啡镇痛作用的调节

Modulation of morphine antinociception in the mouse by endogenous nitric oxide.

Brignola G, Calignano A, Di Rosa M

Department of Experimental Pharmacology, University of Naples Federico II, Italy.

Br J Pharmacol. 1994 Dec;113(4):1372-6. doi: 10.1111/j.1476-5381.1994.tb17149.x.

L-Arginine (100-1000 mg kg-1) administered orally (p.o.) or intraperitoneally (i.p.), but not intracerebroventricularly (i.c.v., 0.08 mg per mouse), reduced the antinociceptive effect of morphine (0.5-10 mg kg-1 s.c.) assessed in mice using three different tests: hot plate, tail-flick and acetic acid-induced writhing. D-Arginine (up to 1000 mg kg-1 p.o. or i.p.) was ineffective. 2. NG-Monomethyl-L-arginine (L-NMMA, 5-50 mg kg-1 i.p.) and NG-nitro-L-arginine methyl ester (L-NAME, 5- 30 mg kg-1 i.p.), but not NG-nitro-D-arginine methyl ester (D-NAME, 30 mg kg-1 i.p.), reversed in all assays the effect of L-arginine on morphine-induced antinociception. 3. Morphine (10 mg kg-1 s.c.), L-arginine (1000 mg kg-1 p.o.) or L-NAME (30 mg kg-1 i.p.), either alone or in combination, did not produce changes in locomotor activity or sensorimotor performance of animals. 4. These results suggest that the L-arginine-nitric oxide pathway plays a modulating role in the morphine-sensitive nociceptive processes.

口服（p.o.）或腹腔注射（i.p.）L-精氨酸（100 - 1000 mg/kg），但脑室内注射（i.c.v.，每只小鼠0.08 mg）无效，可降低吗啡（0.5 - 10 mg/kg，皮下注射）在小鼠中通过三种不同测试评估的镇痛作用：热板法、甩尾法和醋酸诱导扭体法。D-精氨酸（口服或腹腔注射高达1000 mg/kg）无效。2. NG-单甲基-L-精氨酸（L-NMMA，5 - 50 mg/kg，腹腔注射）和NG-硝基-L-精氨酸甲酯（L-NAME，5 - 30 mg/kg，腹腔注射），但NG-硝基-D-精氨酸甲酯（D-NAME，30 mg/kg，腹腔注射）无效，在所有实验中均能逆转L-精氨酸对吗啡诱导镇痛的作用。3. 吗啡（10 mg/kg，皮下注射）、L-精氨酸（1000 mg/kg，口服）或L-NAME（30 mg/kg，腹腔注射），单独或联合使用，均未引起动物运动活性或感觉运动性能的改变。4. 这些结果表明，L-精氨酸-一氧化氮途径在对吗啡敏感的伤害性感受过程中起调节作用。

Modulation of morphine antinociception in the mouse by endogenous nitric oxide.