A comparison of the antinociceptive and behavioral effects of intrathecally administered opiates, alpha-2-adrenergic agonists, and local anesthetics in mice and rats.
This study was undertaken to compare the antinociceptive and behavioral effects of intrathecally administered opiates, alpha-2-adrenergic agonists, and local anesthetics injected by lumbar puncture in the mouse and rat. Antinociception was determined by observing the response to a clamp applied to the tail (Haffner test) of the mouse and by the rat tail-flick test; log dose-response curves for antinociception were generated for each drug in each test. Motor coordination and other behavioral effects were also observed. Morphine and fentanyl (mu-opiate agonists) as well as ethylketocyclazocine (EKC) and U50488H (kappa-opiate agonists), together with buprenorphine (partial mu-opiate agonist) and the alpha-2-adrenergic agonist clonidine, all produced antinociception in both species without causing significant behavioral or motor dysfunctions at antinociceptive doses. Xylazine (also an alpha-2-adrenergic agonist), ketamine, procaine, and lidocaine inhibited responses but only at doses that also produced motor impairment or paralysis. Nalbuphine (mixed opiate agonist-antagonist) was without any effect in both species. These data suggest that the mu- and kappa-opiate agonists and clonidine are the preferred agents for producing antinociception without compromising motor function.
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D000700:Analgesics; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000494:pharmacology; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010147:Pain Measurement; D051381:Rats; D011919:Rats, Inbred Strains
D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D000701:Analgesics, Opioid; D000779:Anesthetics, Local