The Effect of a Selective α 2-Adrenoceptor Antagonist on Pain Behavior of the Rat Varies, Depending on Experimental Parameters

Abstract

Effects of atipamezole, an α 2-adrenoceptor antagonist, in various acute pain tests were studied in the rat. Atipamezole (at doses ⩾0.1 mg/kg IP) and idazoxan, another α 2-adrenoceptor antagonist (2.5 mg/kg, IP), increased licking latency in the hot-plate test. Bilateral administration of atipamezole (10 μg) into the locus coeruleus did not increase licking latency in the hot-plate test. Medetomidine (an α 2-adrenoceptor agonist; 1–3 mg/kg) or repeated preexposures 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 α 2-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.