Tricyclic antidepressants are often effective for the management of persistent pain, and several neurochemical mechanisms have been proposed. The purpose of the present study was to examine the effect of amitriptyline (AMI) in two animal models of inflammatory pain, the formalin test and the bee venom test, and to ascertain the effect of naloxone on amitriptyline analgesia. A single dose of AMI (20 mg/kg) was found to significantly decrease both phases of formalin pain responses and the initial 10 min of bee venom pain responses. However, naloxone (3 mg/kg) had no effect on AMI analgesia in either test. The results show that single doses of AMI can decrease pain behavior in tests of tonic pain and suggest that non-opioid mechanisms may play a role in addition to opioid mechanisms demonstrated in earlier studies.