Rat knee-joint carrageenin incapacitation test: an objective screen for central and peripheral analgesics.
A new behavioral test is described in which quantitation is independent of the observer and is sensitive to all classes of analgesics. A computer-assisted device measures the period during which a rat hind paw fails to touch the surface of a rotating cylinder for 1 min (paw elevation time). Intra-articular injection of carrageenin induces a progressive and dose-dependent incapacitation of the limb. The maximum paw elevation time is attained 3-4 h after carrageenin challenge. The model showed dose-dependent sensitivity to (a) a central acting opiate (morphine, ID50 = 1.5 mg/kg, i.p.), (b) cyclooxygenase inhibitors (indomethacin, ID50 = 0.8 mg/kg, i.p.; diclofenac, ID50 = 0.22 mg/kg, i.p.), and (c) peripheral analgesics which directly antagonize nociceptor hypersensitivity: dipyrone (ID50 = 21 mg/kg, i.p.), N-methyl-nalorphine (ID50 = 14 mg/kg, i.p.) and BW443C (ID50 = 17.5 mg/kg, i.p.). The knee-joint carrageenin incapacitation was also blocked by the sympatholytics, propranolol and guanethidine. After the blockade by either indomethacin or guanethidine, intra-articular injections of prostaglandin E2 or dopamine, respective, reversed carrageenin-induced incapacitation. These results suggest that during inflammatory articular incapacitation cyclooxygenase and sympathomimetic mediators are involved, as has been suggested for the rat paw carrageenin hyperalgesia test and formalin test.
Tonussi
Carlos Rogério
CR
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, Ribeirão Preto, SP, CEP 14049 Brazil.
Ferreira
Sérgio H
SH
D000700:Analgesics / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002351:Carrageenan / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D004298:Dopamine / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D007274:Injections, Intraperitoneal; D007719:Knee Joint / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013565:Sympatholytics / Q000494:pharmacology; D016138:Walking
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013565:Sympatholytics; D002351:Carrageenan; D015232:Dinoprostone; D004298:Dopamine