INTRATHECAL SOMATOSTATIN IN RATS - ANTINOCICEPTION ONLY IN THE PRESENCE OF TOXIC EFFECTS
INTRATHECAL SOMATOSTATIN IN RATS - ANTINOCICEPTION ONLY IN THE PRESENCE OF TOXIC EFFECTS
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DOI：
10.1097/00000542-198805000-00011
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发表时间：
1988-05-01
期刊：
影响因子：
8.8
通讯作者：
YAKSH, TL
中科院分区：
文献类型：
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作者：
GAUMANN, DM;YAKSH, TL
在慢性植入腰段鞘内导管的大鼠中评估了鞘内（i.t.）注射生长抑素（SST）（10、30和100微克）对痛觉、自主神经和运动功能的影响。10微克和30微克SST鞘内注射对皮肤热痛觉（热板和甩尾反应）没有影响。与生理盐水对照组相比，30微克SST鞘内注射不影响内脏化学刺激诱发的痛觉（醋酸扭体试验）。接受100微克SST鞘内注射的大鼠总是表现出暂时性或永久性后肢运动功能障碍，在最严重的情况下出现弛缓性麻痹（运动功能测试、肌电图反应）。观察到甩尾和足捏反应在不同程度上被阻断，且仅在存在可检测到的运动损伤时出现。在40只接受100微克SST鞘内注射的动物中，25%在注射后10分钟内死亡。在慢性植入膀胱导管的大鼠中评估了SST对容量诱发排尿反射的影响。在接受30微克SST鞘内注射的9只存活动物中有3只，以及所有接受额外60微克SST鞘内注射的动物，都表现出排尿反射完全阻断以及随后出现膀胱溢流。脊髓的组织学检查显示，在5只接受30微克SST鞘内注射的动物中有4只出现轻度炎症反应。在接受100微克SST鞘内注射的动物（n = 4）的脊髓中，观察到在炎症反应存在的情况下，腹角和背角出现轻度或重度核溶解。目前的实验清楚地表明，SST对大鼠具有高度毒性作用，在抗痛觉和运动功能障碍之间没有安全边际。
Effects of intrathecal (i.t.) somatostatin (SST) (10, 30, and 100 .mu.g) on nociception, and autonomic and motor function were evaluated in rats with chronically implanted lumbar i.t. catheters. Doses of 10 and 30 .mu.g SST i.t. had no effect on thermal cutaneous nociception, (hot plate and tail flick response). Thirty micrograms SST i.t. did not affect the visceral chemical evoked nociception (acetic acid writhing test) as compared to saline control groups. Rats treated with 100 .mu.g 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 .mu.g 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 .mu.g SST i.t. and all animals receiving an additional dose of 60 .mu.g 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 .mu.g SST i.t. In spinal cords of animals, which had received 100 .mu.g SST i.t. (n = 4), mild or severe nucleolysis of ventral and dorsal horns in the presence of inflammatory reaction was observed. Present experients clearly demonstrate highly toxic effects of SST in rats with no margin of safety between antinociception and motor dysfunction.