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.