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.