Effect of xylazine and yohimbine on the phasic pain during the estrous cycle in the rat

The aim of the present study was to investigate the effect of α2-adrenergic agonist (xylazine) and antagonist (yohimbine) on phasic pain during estrous cycle in female rats. Adult female rats weighing 180-220 g were kept under controlled temperature (21-24°C) and light/dark conditions (light on at 6:00 a.m. and light off at 6:00 p.m.). Animals were divided into four groups: 1) control group which received 0.3 ml of normal saline by intraperitoneal (IP) route; 2) IP experimental group which received 0.3 ml xylazine 3, 4.5 and 6 mg/kg and yohimbine 1, 2 and 4 mg/kg by IP route; 3) sham group which received 2 ml of artificial cerebrospinal fluid by intra cerebral ventricle (ICV) route and 4) ICV experimental which received 2 ml xylazine 10 and 20 mg/rat and yohimbine 5 and 10 mg/rat by ICV route. Cannulae were implanted into the left lateral ventricle using stereotaxic method. Pain sensitivity was measured by tail flick test, which was performed before injection, 15 and 30 min after injection in all groups. Xylazine decreased pain sensitivity significantly (P<0.05) during the estrous cycle; while higher analgesia was observed in the proestrus phase for IP and ICV routes. Yohimbine increased pain sensitivity significantly (P<0.05) during the estrous cycle; while higher hyperalgesia was observed in the metestrus phase for IP and ICV route groups. There was interaction (P<0.05) between endogenous steroids and the α2-adrenergic system in the modulation of phasic pain sensitivity.