Effects of
atipamezole, an alpha2-adrenoceptor antagonist, in various
acute pain tests were studied in the rat.
Atipamezole (at doses > or = 0.1 mg/kg I.P.) and
idazoxan, another alpha2-adrenoceptor antagonist (2.5 mg/kg, I.P.), increased licking latency in the hot-plate test. Bilateral administration of
atipamezole (10 microg) into the locus coeruleus did not increase licking latency in the hot-plate test.
Medetomidine (an alpha2-
adrenoceptor agonist; 1-3 mg/kg) or repeated pre-exposures to the testing apparatus reversed the effect of
atipamezole (1.5 mg/kg) in the hot-plate test.
Atipamezole also increased the latency to mechanically induced licking/biting response at a dose of 1.5 mg/kg, but not at lower doses. In the heat-induced tail-flick test, in contrast,
atipamezole at doses of 0.1 and 1.5 mg/kg produced a
medetomidine-reversible decrease of response latencies. This facilitation of the tail-flick response disappeared if the intensity of the heat stimulus was high. At a dose range from 0.03 to 1.5 mg/kg
atipamezole did not significantly alter the paw withdrawal latency to noxious mechanical stimulation, nor
pain behavior in the
formalin test. Responses to nociceptive spinal dorsal horn neurons were not modulated by
atipamezole (1 mg/kg) in anesthetized spinalized rats. The results indicate that an alpha2-adrenoceptor antagonist may have variable effects in behavioral
pain tests, depending on habituation of the experimental animals to the testing conditions, the dose of the
drug, the type of behavioral response and the submodality or the intensity of the noxious test stimulus. The
atipamezole-induced changes in
pain behavior observed in this study may rather be explained due to action on motor expression of
pain than due to modulation of nociception.