Intrathecal somatostatin in rats: antinociception only in the presence of toxic effects.

Effects of intrathecal (i.t.) somatostatin (SST) (10, 30, and 100 micrograms) on nociception, and autonomic and motor function were evaluated in rats with chronically implanted lumbar i.t. catheters. Doses of 10 and 30 micrograms SST i.t. had no effect on thermal cutaneous nociception, (hot plate and tail flick response). Thirty micrograms SST i.t. did not effect the visceral chemical evoked nociception (acetic acid writhing test) as compared to saline control groups. Rats treated with 100 micrograms SST i.t. invariably showed temporary or permanent hindlimb motor dysfunction, with flaccid paralysis in the most severe cases (motor function tests, electromyographic response). Blockade of the tail flick and foot pinch response was observed to a variable degree, and only in the presence of detectable motor impairment. Out of 40 animals injected with 100 micrograms SST i.t., 25% died within 10 min following injection. Effects of SST on the volume evoked micturition reflex were assessed in rats with chronically implanted bladder catheters. Three of the nine surviving animals receiving 30 micrograms SST i.t. and all animals receiving an additional dose of 60 micrograms SST i.t. showed a complete block of the micturition reflex and subsequent development of an overflow bladder. Histological examination of spinal cords revealed a mild inflammatory response in four out of five animals treated with 30 micrograms SST i.t. In spinal cords of animals, which had received 100 micrograms SST i.t. (n = 4), mild or severe nucleolysis of ventral and dorsal horns in the presence of inflammatory reaction was observed. Present experiments clearly demonstrate highly toxic effects of SST in rats with no margin of safety between antinociception and motor dysfunction.