Qiu C, Sora I, Ren K, Uhl G, Dubner R
Department of Oral and Craniofacial Biological Sciences, University of Maryland Dental School, Room 5E-08, 666 West Baltimore Street, Baltimore, MD 21201, USA.
Eur J Pharmacol. 2000 Jan 10;387(2):163-9. doi: 10.1016/s0014-2999(99)00813-4.
Inflammatory hyperalgesia was induced in wild-type, heterozygous and mu-opioid receptor knockout mice after an intraplantar injection of complete Freund's adjuvant. micro-Opioid receptor knockout mice exhibited faster recovery from hyperalgesia as compared to heterozygous (P<0.05) and wild-type (P<0.01) mice. Naloxone restored hyperalgesia in all genotypes. Naltrindole (delta-opioid receptor-selective antagonist) partially restored the hyperalgesia only in mu-opioid receptor knockout mice (P<0.001). Nor-binaltorphimine (kappa-opioid receptor-selective antagonist) had no effect. The mu-opioid receptor-selective agonist, [D-Ala(2), MePhe(4),Gly-ol(5)]enkephalin (DAMGO), reduced the hyperalgesia in heterozygous and wild-type but not in mu-opioid receptor knockout mice while U69,593 ¿(+)-(5alpha,7alpha, 8beta)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4. 5]dec-8-yl]-benzeneacetamide, kappa-opioid receptor-selective¿ produced similar effects in all mice. The delta-opioid receptor-selective agonists, [D-Pen(2), D-Pen(5)]enkephalin (DPDPE) and deltorphin ([D-Ala(2)]deltrophin-II), produced significantly greater antihyperalgesia in knockout mice (P<0.05). The findings suggest that mu-opioid receptors may be involved in the persistence of inflammatory hyperalgesia and that a delta-opioid receptor-mediated compensatory mechanism in the absence of the mu-opioid receptor is activated by persistent hyperalgesia.
在野生型、杂合子和μ-阿片受体基因敲除小鼠的足底注射完全弗氏佐剂后诱导炎性痛觉过敏。与杂合子小鼠（P<0.05）和野生型小鼠（P<0.01）相比，μ-阿片受体基因敲除小鼠的痛觉过敏恢复更快。纳洛酮可恢复所有基因型小鼠的痛觉过敏。纳曲吲哚（δ-阿片受体选择性拮抗剂）仅在μ-阿片受体基因敲除小鼠中部分恢复了痛觉过敏（P<0.001）。nor-环丙甲羟二氢吗啡酮（κ-阿片受体选择性拮抗剂）没有效果。μ-阿片受体选择性激动剂[D-Ala(2)，MePhe(4)，Gly-ol(5)]脑啡肽（DAMGO）可减轻杂合子和野生型小鼠的痛觉过敏，但对μ-阿片受体基因敲除小鼠无效，而κ-阿片受体选择性激动剂U69,593 [（+）-（5α，7α，8β）-N-甲基-N-[7-（1-吡咯烷基）-1-氧杂螺[4.5]癸-8-基]-苯乙酰胺]在所有小鼠中产生类似效果。δ-阿片受体选择性激动剂[D-Pen(2)，D-Pen(5)]脑啡肽（DPDPE）和强啡肽（[D-Ala(2)]强啡肽-II）在基因敲除小鼠中产生了显著更强的抗痛觉过敏作用（P<0.05）。这些发现表明，μ-阿片受体可能参与炎性痛觉过敏的持续存在，并且在没有μ-阿片受体的情况下，由持续的痛觉过敏激活了一种δ-阿片受体介导的代偿机制。
