Augmentation of central and peripheral morphine analgesia by desipramine

Using the rat tail-flick method to assess analgetic efficacy, the effects of desipramine (DMI) on analgesia produced by either systemic or central (i.e., periaqueductal gray) administration of morphine sulfate (MS) were evaluated. Pretreatment of rats with DMI (30 mg/kg, s.c.) increased the duration of analgesia following systemic injection of MS (5.0 mg/kg, s.c.) from 50 min to 150 min, but did not significantly alter the peak analgetic response. A similar but less marked effect was observed following a 2.5 mg/kg dose of MS. Pretreatment with DMI likewise extended the duration of effective analgesia following microinjection of 2.5 μg and 5.0 μg MS into the ventrolateral periaqueductal gray region (VLPAG). In addition, the maximal analgetic response to the 5.0 μg dose of MS was increased by DMI. These results suggest that potentiation of morphine-induced analgesia by DMI cannot be ascribed solely to a peripheral interaction (i.e. inhibition of hepatic biotransformation) but probably involves a central interaction as well.