Pharmacological pain management is necessary under many clinical situations, but in donkeys little information on analgesic drugs is available. This controlled, randomised, crossover, Latin-square, operator-blinded study aimed to assess and compare the hypoalgesic effects of intravenously administered saline and five α2-adrenoceptor agonists on mechanical nociceptive thresholds (MNT) in donkeys. Areas under the threshold change versus time curve values for 0–30, 30–60, 60–90 and 90–120 minutes postdrug administration were used to compare the effect of treatment. As compared with saline, which did not increase MNT, the overall degree of mechanical hypoalgesia induced by xylazine (1.1 mg/kg), detomidine (20 μg/kg), medetomidine (5 μg/kg) and dexmedetomidine (3.5 μg/kg) was limited to 0–60 minutes, and that of romifidine (100 μg/kg) to 0–120 minutes. Although there were no significant differences between the five α2-adrenoceptor agonists during the first 30 minutes postadministration, hypoalgesia induced by xylazine and dexmedetomidine was significantly less intense than that achieved by detomidine and/or romifidine from 30 to 60 minutes. Differences in the overall degree of hypoalgesia induced by each of the α2-adrenoceptor agonists may influence veterinary surgeons towards choosing a particular drug over others for a particular donkey patient.