Schäfer M, Imai Y, Uhl G R, Stein C
Division of Intramural Research, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
Eur J Pharmacol. 1995 Jun 12;279(2-3):165-9. doi: 10.1016/0014-2999(95)00150-j.
mu-Opioid receptor agonist [D-Ala2,NMe-Phe4,Gly5-ol]enkephalin (DAMGO)-induced peripheral analgesic effects occur early in hindpaws inoculated with Freund's complete adjuvant and increase in parallel to the development of inflammatory signs. Antagonism of these effects by beta-funaltrexamine, an irreversible mu-opioid receptor antagonist, suggests that the effective number of peripheral opioid receptors does not increase during early stages, but does so at later stages of the inflammation. As determined by a ribonuclease protection assay, mu-opioid receptor mRNA in dorsal root ganglia is abundant in untreated animals, but does not significantly increase following inflammation. Thus, peripheral analgesic efficacy of DAMGO is not correlated with transcription or number of mu-opioid receptors at early inflammatory stages. At later stages, however, the number of peripheral mu-opioid receptors appears to increase and may enhance opioid efficacy.
μ-阿片受体激动剂[D-丙氨酸2，N-甲基苯丙氨酸4，甘氨酸5-醇]脑啡肽（DAMGO）诱导的外周镇痛作用在接种弗氏完全佐剂的后爪中早期出现，并与炎症体征的发展平行增加。不可逆的μ-阿片受体拮抗剂β-氟纳曲明对这些作用的拮抗表明，外周阿片受体的有效数量在炎症早期不增加，但在炎症后期会增加。通过核糖核酸酶保护试验确定，背根神经节中的μ-阿片受体mRNA在未治疗的动物中丰富，但在炎症后没有显著增加。因此，DAMGO的外周镇痛效果与炎症早期μ-阿片受体的转录或数量无关。然而，在后期，外周μ-阿片受体的数量似乎增加，可能会增强阿片类药物的疗效。
