Prolonged spinal analgesia in the rat with the alpha-adrenoceptor agonist oxymetazoline

The acute intrathecal (i.t.) injection of 50, 100, 200, 250 and 300 nmol of oxymetazoline produced dose-dependent antinociception in rats assessed by tail flick and paw pressure tests. Significant antinociception was observed with all doses of oxymetazoline except 50 nmol in the paw pressure test. The ED50 values for i.t. oxymetazoline in the tail flick and paw pressure tests were 120 nmol (95% CI: 76-178 nmol) and 148 nmol (95% CI: 120-186 nmol), respectively. Oxymetazoline had a long duration of action; a single i.t. dose of 100 nmol significantly elevated tail flick latency and paw pressure threshold for 8 h. The alpha-adrenoceptor antagonist phentolamine, given i.t. 1 h after oxymetazoline, attenuated the antinociceptive effect in a dose-dependent manner. Phentolamine (50 micrograms i.t.) produced almost complete antagonism in the tail flick and paw pressure tests. These data indicate that oxymetazoline produces long lasting antinociception in the rat following i.t. injection, and that the effect is mediated by alpha-adrenoceptors in the spinal cord.