Kamei J, Nagase H
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Tokyo 142-8501, Shinagawa, Japan.
Eur J Pharmacol. 2001 Apr 20;418(1-2):141-5. doi: 10.1016/s0014-2999(01)00941-4.
We examined the possibility that scratching induced by norbinaltorphimine, a selective kappa-opioid receptor antagonist, is due to an itch sensation, using compound 48/80 as control pruritogenic agent. When norbinaltorphimine was injected s.c. into the rostral back, mice scratched the skin around the injection site with their hind paws. Although the intensity of the scratching could not be compared because the dose and injection route were different, the character and time course of the scratching behavior induced by compound 48/80 injected i.d. were similar to those with norbinaltorphimine. The scratching behavior induced by norbinaltorphimine was dose-dependently and significantly inhibited by pretreatment with chlorpheniramine. Compound 48/80-induced scratching was also dose-dependently and significantly inhibited by p.o. pretreatment with chlorpheniramine. The scratching behavior induced by norbinaltorphimine was dose-dependently and significantly inhibited by pretreatment with U-50,488H (trans-(+/-)-2-(3,4-dichlorophenyl)-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] acetamide methansulfonate), a kappa-opioid receptor agonist. Unexpectedly, the scratching behavior induced by compound 48/80 was also dose-dependently and significantly reduced by pretreatment with U-50,488H. These results suggest that the injection of norbinaltorphimine into the rostral back of the mouse elicited scratching, which may be an itch-associated response. Furthermore, the scratching behavior produced by norbinaltorphimine may be due in part to the release of histamine followed by antagonism of kappa-opioid receptors.
我们使用化合物48/80作为对照致痒剂，研究了选择性κ-阿片受体拮抗剂诺宾那托啡诱导的抓挠是否源于瘙痒感。当将诺宾那托啡皮下注射到小鼠头背部时，小鼠会用后爪抓挠注射部位周围的皮肤。尽管由于剂量和注射途径不同，无法比较抓挠的强度，但皮内注射化合物48/80所诱导的抓挠行为的特征和时间进程与诺宾那托啡诱导的相似。氯苯那敏预处理能剂量依赖性且显著抑制诺宾那托啡诱导的抓挠行为。口服氯苯那敏预处理也能剂量依赖性且显著抑制化合物48/80诱导的抓挠行为。κ-阿片受体激动剂U-50,488H（反式-(+/-)-2-(3,4-二氯苯基)-N-甲基-N-[2-(1-吡咯烷基)环己基]乙酰胺甲磺酸盐）预处理能剂量依赖性且显著抑制诺宾那托啡诱导的抓挠行为。出乎意料的是，U-50,488H预处理也能剂量依赖性且显著减少化合物48/80诱导的抓挠行为。这些结果表明，向小鼠头背部注射诺宾那托啡会引发抓挠，这可能是一种与瘙痒相关的反应。此外，诺宾那托啡产生的抓挠行为可能部分归因于组胺的释放以及随后κ-阿片受体的拮抗作用。
