Involvement of opioidergic and alpha2-adrenergic mechanisms in the central analgesic effects of non-steroidal anti-inflammatory drugs in sheep.
The level within the central nervous system where non-steroidal anti-inflammatory drugs (NSAIDs) produce analgesia and the mechanisms by which they mediate this effect are still uncertain. This study assessed the central analgesic effects of ketoprofen, phenylbutazone, salicylic acid and tolfenamic acid in sheep implanted with indwelling intrathecal (i.t.) catheters and submitted to mechanical noxious stimulation. The sheep received i.t. cumulative concentrations (0.375-200 microM; 100 microL) as well as a single intravenous (i.v.) dose (3, 8, 10 and 2 mg/kg, respectively) of each NSAID. The sheep were also given i.t. naloxone (5.49 mM; 100 microL) and atipamezole (4.03 mM; 100 microL) prior to i.v. ketoprofen. None of the i.t. NSAIDs increased mechanical thresholds. Intravenously, only ketoprofen and tolfenamic acid raised the pain thresholds. The hypoalgesic effect of i.v. ketoprofen was prevented by i.t. naloxone or atipamezole. Although NSAIDs had no direct effect on the spinal cord, their analgesic action appeared to be spinally mediated.
Lizarraga
Ignacio
I
Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Private Bag 11222, Palmerston North, New Zealand. I.Lizarraga@massey.ac.nz
Chambers
J P
JP
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007275:Injections, Intravenous; D007278:Injections, Spinal; D007660:Ketoprofen / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010653:Phenylbutazone / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D020156:Salicylic Acid / Q000494:pharmacology; D012756:Sheep / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D009292:Narcotic Antagonists; D018341:Receptors, Adrenergic, alpha-2; D011957:Receptors, Opioid; D062367:ortho-Aminobenzoates; C050701:atipamezole; D009270:Naloxone; C009500:tolfenamic acid; D007660:Ketoprofen; D010653:Phenylbutazone; D020156:Salicylic Acid