Do acute or chronic tricyclic antidepressants modify morphine antinociception in arthritic rats?

In a chronic pain model, the arthritic rat, tricyclic antidepressants (TCAs) have been shown to clearly reduce behavioural signs of nociception. In the present work, using a test of acute nociception (vocalization threshold to graded foot pressure) in the same model, we evaluated the possible potentiation of morphine analgesia by 2 TCAs: amitriptyline (AMIT) and imipramine (IMIP). Using this test of acute nociception, we failed to demonstrate any analgesic effect of AMIT or IMIP given either acutely or chronically. We also failed to demonstrate any potentiation of morphine by these compounds. On the contrary, we found a significant decrease of morphine antinociception after acute AMIT administration and a tendency towards diminution with both TCAs given chronically. These results appear to temper enthusiasm for human application of this combination. They also indicate that careful further studies in a chronic pain model using behaviour evaluations are necessary before definite conclusions can be drawn concerning TCAs/opiate interaction.