Arrigo-Reina R
Institute of Pharmacology and Pharmacognosy, Faculty of Pharmacy, University of Catania, Italy.
Agents Actions. 1990 Apr;30(1-2):210-2. doi: 10.1007/BF01969040.
The role of neural histamine in morphine-analgesia and in morphine-induced potentiation of stress analgesia was studied. Pretreatment of rats with alpha-fluoromethylhistidine (alpha-FMH) (200 micrograms i.c.v./rat; daily for five days) increased the analgesic potency of morphine, centrally or peripherally injected, in the tail-flick assay. This increase was significantly blocked by i.c.v. or i.p. beta-funaltrexamine (beta-FNA) a mu selective irreversible opioid receptor antagonist, whereas i.c.v. injected naltrexone did not block the increased analgesic potency of the i.c.v. morphine. Rats subjected to cold-restrained stress (60 min at 4 degrees C) showed increased tail-flick latency, compared to the unstressed group. The analgesic potency of morphine was significantly greater in rats subjected to restraint with respect to unstressed rats. However, the inhibition of histamine biosynthesis by alpha-FMH significantly reduced cold-restraint analgesia in controls, and also inhibited the analgesic efficacy of the opiate. These results indicate that neural histamine may be responsible for pain response modifications observed in rats subjected to cold-restraint conditions, and of morphine-potentiation of stress analgesia. The data also suggest a close association between increased analgesic potency of morphine and inhibition of histaminergic effects, possibly implying a functional supersensitivity and an increase in opioid receptors.
研究了神经组胺在吗啡镇痛以及吗啡诱导的应激镇痛增强作用中的作用。用α-氟甲基组氨酸（α-FMH）（200微克/大鼠，脑室内注射；每日一次，共五天）预处理大鼠，可增强在甩尾试验中脑室内或外周注射吗啡的镇痛效力。这种增强作用可被脑室内或腹腔注射的μ选择性不可逆阿片受体拮抗剂β-芬基曲马胺（β-FNA）显著阻断，而脑室内注射的纳曲酮则不能阻断脑室内注射吗啡增强的镇痛效力。与未受应激的组相比，经受冷束缚应激（4℃下60分钟）的大鼠甩尾潜伏期延长。在经受束缚的大鼠中，吗啡的镇痛效力相对于未受应激的大鼠显著增强。然而，α-FMH对组胺生物合成的抑制显著降低了对照组的冷束缚镇痛作用，并且也抑制了阿片类药物的镇痛效果。这些结果表明，神经组胺可能是在经受冷束缚条件的大鼠中观察到的疼痛反应改变以及吗啡增强应激镇痛作用的原因。数据还表明，吗啡镇痛效力增强与组胺能效应抑制之间存在密切关联，这可能意味着功能超敏以及阿片受体增加。
