Intrathecal somatostatin in cat and mouse studies on pain, motor behavior, and histopathology.

Effects of intrathecal (i.t.) somatostatin (SST) on nociception, motor function, and spinal cord pathology were evaluated in cats and mice. Cats chronically implanted with i.t. lumbar catheters received either a single injection of 2 mg SST i.t. (group I, N = 4), four repetitive injections on consecutive days of 2 mg SST i.t. (group II, N = 4) or saline i.t. (group III, N = 2). No analgesic effects were observed following single or repeated SST injections as evaluated by the skin twitch response. However, significant impairment of hind leg motor function ranging from unbalanced gait to paralysis was observed following the first SST i.t. injection. Histological examination of spinal cords six days after the first SST injection in group II showed multiple pyknotic neurons in all cats. Some cats showed focal demyelination in the posterior column of the spinal cord white matter. Mice received a single percutaneous injection of 50 micrograms SST i.t. (group I, N = 7), 5 micrograms SST i.t. (group II, N = 3), or saline i.t., (group III, N = 5). No analgesic effects were observed in groups II and III as evaluated by the hot plate (HP) and tail flick (TF) tests. Injection of 50 micrograms SST i.t. (group I) caused reversible flaccid hind leg paralysis in all mice and concomitant increases in HP and TF latencies. Histologic examination revealed focal demyelination in the spinal cord in three out of seven mice in this group. Present data substantiate neurotoxic effects of i.t. SST and lack of behaviorally defined antinociception at innocuous dosages.