Heyman J S, Mosberg H I, Porreca F
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson 85724.
NIDA Res Monogr. 1986;75:442-5.
Possible involvement of cerebral delta opioid receptors in antinociceptive processes was studied in a test utilizing heat as the noxious thermal stimulus. The investigation focused on selective agonists and antagonists for mu and delta opioid receptors. Morphine and [D-Ala2,NMPhe4, Gly-ol]enkephalin (DAGO) were used as agonists for the mu receptor while [D-Pen2,D-Pen5]enkephalin (DPDPE) was the agonist for the delta receptor. Two approaches were employed: first, the intracerebroventricular (i.c.v.) analgesic activity of the agonists was determined in the absence, and in the presence of graded i.c.v. doses of the selective delta antagonist, ICI 174,864 (N,N diallyl-Tyr-Aib-Aib-Phe-Leu-OH) (where Aib is alpha-aminoisobutyric acid); second, acute tolerance to morphine was produced and the possible presence of acute cross-tolerance between subcutaneous (s.c.) morphine and the delta agonist investigated. ICI 174,864 antagonized the analgesia produced by DPDPE, but not that resulting from morphine or DAGO. Morphine pretreatment resulted in the development of acute tolerance to i.c.v. morphine, and acute cross-tolerance to i.c.v. DAGO, but not to i.c.v. DPDPE. These results provide evidence that both cerebral delta and mu opioid receptors are responsible for the mediation of analgesia in tests utilizing heat as the nociceptive stimulus.
在一项以热作为有害热刺激的试验中，研究了脑内δ阿片受体在抗伤害感受过程中可能的作用。该研究聚焦于μ和δ阿片受体的选择性激动剂和拮抗剂。吗啡和[D - Ala2，N - MePhe4，Gly - ol]脑啡肽（DAGO）用作μ受体激动剂，而[D - Pen2，D - Pen5]脑啡肽（DPDPE）是δ受体激动剂。采用了两种方法：第一，在不存在以及存在梯度脑室注射（i.c.v.）剂量的选择性δ拮抗剂ICI 174,864（N，N - 二烯丙基 - Tyr - Aib - Aib - Phe - Leu - OH）（其中Aib是α - 氨基异丁酸）的情况下，测定激动剂的脑室镇痛活性；第二，产生对吗啡的急性耐受性，并研究皮下注射（s.c.）吗啡与所研究的δ激动剂之间可能存在的急性交叉耐受性。ICI 174,864拮抗DPDPE产生的镇痛作用，但不拮抗吗啡或DAGO产生的镇痛作用。吗啡预处理导致对脑室注射吗啡产生急性耐受性，对脑室注射DAGO产生急性交叉耐受性，但对脑室注射DPDPE不产生急性交叉耐受性。这些结果提供了证据，表明在以热作为伤害性刺激的试验中，脑内δ和μ阿片受体均参与镇痛作用的介导。
