[Differentiation of antinociceptive effects of mu, delta and kappa agonists using heat, chemical and mechanical nociception].
The antinociceptive properties of mu (D-Ala2, N-Me-Phe4, Gly5-ol, enkephalin, DAGO), delta (D-Ala2, D-leu5, enkephalin, DADL) and kappa (dynorphin, DYN) were assessed using hot plate (heat), acetic acid-induced writhing (chemical) and tail pinch (mechanical) assays in mice. Test drug and control treatments were given by cisternal injection in a dose volume of 10 microliters.mouse-1. DAGO and DADL produced steep dose-response lines in all the tests. DYN did not produce a consistent antinociceptive effect on the tail pinch test. Utilizing these three different types of assays, the rank order of antinociceptive potency for these three opioids was DAGO > DADL > DYN. The responses to the hot plate and writhing assays were completely inhibited by the same dose of DAGO. DADL displayed equal antinociceptive effects in the hot plate and writhing tests. In the tail pinch assay, however, antinociceptive potency of DAGO was 1/3 less than in other two assays, and DADL was also 1/10 less than in the others. The rank order of antinociceptive potency for DYN in different noxia was the writhing > hot plate >> tail pinch. It was concluded that there are differences in the potency of mu-, delta- and kappa-agonists even when the intensities of chemical and heat noxia are equal. It was also proposed that antinociceptive potencies against mechanical noxia is greatly different among mu-, delta- and kappa-agonists.
Murakawa
K
K
Department of Anesthesiology, Hyogo College of Medicine, Nishinomiya.
Noma
K
K
Matsuda
M
M
Maeda
S
S
Tashiro
C
C
Izumi
R
R
D019342:Acetic Acid; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D006358:Hot Temperature; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D010812:Physical Stimulation; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013268:Stimulation, Chemical; D013314:Stress, Mechanical
D000701:Analgesics, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D019342:Acetic Acid