Effect of intrathecal tizanidine on antinociception and blood pressure in the rat

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Abstract
Experiments were performed in rats to determine if the .alpha.2-adrenergic agonist tizanidine has an antinociceptive effect when injected intrathecally, and whether the analgesia is accompanied by changes in blood pressure. Rats were chronically implanted with catheters in the lumbar subarachnoid space. Antinociception was evaluated in conscious rats with the tail-flick test. Increasing tizanidine doses produced increases in analgesic efficacy, with 25 .mu.g producing a significant long-lasting antinociception. This tail-flick analgesia was very similar to that produced by clonidine (25 .mu.g) and morphine (8 .mu.g) in peak effect and duration. Doses as high as 250 .mu.g produced only a transient hind limb motor dysfunction in 43% of the animals. Daily injections of 25 .mu.g tizanidine over 5 days produced a decrease in antinociception, with the peak effect at day 5 at 59% of that at day 1. Blood pressure, in rats lilghtly anesthetized with halothane, was not affected by tizanidine injections up to 250 .mu.g. Tizanidine appears to be a promising non-opiate analgesic for intrathecal usage.