Evaluation of opioid-induced antinociceptive effects in anaesthetized and conscious animals.
1. The activity profiles of opioid agonists and non-steroidal analgesic agents have been compared against different nociceptive stimuli in the mouse and rat. 2. Opioid agonists, but not non-steroidal analgesic agents, inhibited reflex depressor responses evoked by visceral distension in anaesthetized rats. The ranked order of potency of opioids in the visceral distension reflex was identical to that observed in the mouse writhing assay. 3. Opioid-induced inhibition of reflex depressor responses and writhing was observed with ligands acting on mu- and kappa-, but not delta-receptors. Antinociceptive activity of opioids in the rat cold water tail-flick assay was restricted to mu-receptor agonists. 4. Morphine- and ethylketocyclazocine (EKC)-induced inhibition of the visceral distension reflex was blocked by naloxone, but not by the quaternary opioid antagonist N-methylnalorphine. 5. Direct cardiovascular effects were observed with ligands for the mu- and kappa-receptor. Blood pressure changes induced by morphine and Tyr.D-Ala.Gly.MePhe.Gly-ol (DAGOL), but not EKC, were blocked by N-methylnalorphine. Pretreatment with 16-methylcyprenorphine (M8008) antagonized morphine-, DAGOL- and EKC-induced cardiovascular effects, but not those of dynorphin-(1-13) or U50488. 6. It is concluded that reflex circulatory responses evoked by visceral distension in anaesthetized rats are a valid index for the evaluation of opioid-induced antinociception. A simultaneous assessment of cardiovascular effects of opioids was achieved.
Clark
S J
SJ
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent.
Follenfant
R L
RL
Smith
T W
TW
D000700:Analgesics; D000758:Anesthesia; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051379:Mice; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000378:metabolism; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu