Effects of Venlafaxine & Methadone Alone and in Combination With Spontaneous Morphine Withdrawal Syndrome & Pain Sensation in Rats

introduction: methadone has been used as a drug to detoxify opioid tolerance. naloxaneprecipitated morphine withdrawal behaviours were attenuated by venlafaxine as an antidepressant.on the contrary, after detoxifying the opioids, spontaneous withdrawal syndrome may occur withpain sensitivity. therefore the present study aimed to examine the effects of chronic methadone(70 mg/kg, in drinking water, 7 days), venlafaxine (80 mg/kg/day, intraperitoneally, 7 days) andtheir combinations with the spontaneous morphine withdrawal syndrome and pain sensitivity. methods: twenty eight young male sprague-dawley rats were randomly divided into 4groups: control, venlafaxine treated, methadone treated and venlafaxine + methadone treated.morphine sulfate (10 mg/kg/day, subcutaneously, 4 days) was injected to all animals. thenprimary withdrawal behaviours and tail flick test were performed. the test was then followedby methadone or its vehicle administration. second intervention was venlafaxine or its vehicleinjection. then final withdrawal behaviours and tail flick test were performed. results: combination of chronic methadone substitution and venlafaxine administration,significantly reduced freezing behaviour of spontaneous morphine withdrawal syndrome(p<0.01, 379±144%). chronic methadone administration (p<0.05, 35±8% difference withvenlafaxine treated group) induced hyperalgesia. a positive correlation (p=0.001, +63%) wasobserved between the animals final freezing scores and their response latencies to the painfulstimulus. discussion: combination of chronic methadone and venlafaxine administrations reducesfreezing withdrawal behaviour. further investigations on analgesic interventions are needed toovercome this hyperalgesia.