Site- and test-dependent antinociceptive efficacy of amitriptyline in rats

The antinociceptive efficacy of systemic- (IV), spinal- (IT), and global supraspinal (ICV)-administered amitriptyline (AMIT) was compared in three different tests for nociception: the hot-plate test, the tail-flick test, and the withdrawal reflex test. Systemic AMIT inhibited the responses in each of the three tests, with distinct dose-effect relationships. Spinal AMIT reduced in a dose-dependent fashion the force of withdrawal to noxious electrical stimulation but was ineffective in the hot-plate test and facilitated the responses in the tail-flick test. Supraspinal AMIT inhibited in dose-dependent fashion the response to the stimulus of the hot plate, reduced the force of withdrawal after a dose that was effective by the IV route, and again facilitated the responses in the tail-flick test. The results suggest that spinal sites mediate the inhibition of the withdrawal reflex and the supraspinal site the inhibition of the hot-plate test. Two conclusion are drawn: First, AMIT's site of action varies among the pain modalities; and, second, augmentation of the reactions can occur. The complex interaction accords with the clinical experience that the benefits of AMIT in pain treatment are hard to predict.