The effect of local injection of amitriptyline on the formalin test model of pain

Amitriptyline, a tricyclic antidepressant agent is used as one of the analgesic drugs in different kinds of pain. In the present study the effect of local (subcutaneous) injection of amitriptyline (50 and 100 µg) on the acute and chronic pain using formalin test, was investigated. Our data show that local injection of amitriptyline to the paw receiving formalin, causes a decrease in pain in both phasic and tonic phases of formalin test. On the other hand, in the group that this drug was injected (100 µg) to the contralateral paw, no significant change was observed in the pain score with respect to the control group. Therefore, it seems that the observed effect is due to the local action of amitriptyline and not as a result of its systemic effect. Considering the above-mentioned results, it is concluded that: 1) Amitriptyline acts like a local anesthetic in both acute and tonic phases of formalin test. 2) The mechanism of analgesia in the acute phase is probably caused by sodium channel blockade. 3) The analgesic effect of amitriptyline in the tonic phase of formalin test might be due to its antihistaminic and anti-inflammatory effects at the peripheral level, and also is due to the changes in the CNS plasticity which occurs during the acute phase.