蛛网膜下腔注射氯胺酮对神经痛大鼠痛行为的影响

The effect of intrathecal ketamine on pain-related behaviors of rats with neuropathic pain

目的 观察蛛网膜下腔应用氯胺酮对慢性压迫性损伤所致的神经痛大鼠痛行为的影响。方法 SD雄性大鼠 4 0只制备慢性神经痛模型 ,随机分为四组 ,每只大鼠蛛网膜下腔注射 5 μl成分不同的液体。A组 :神经结扎前 30min及术后 3d每天蛛网膜下腔注射氯胺酮 5 μg ,B组 :神经结扎前 30min及术后 3d每天蛛网膜下腔注射氯胺酮 5 0 μg ,C组 :神经结扎术后第 4d蛛网膜下腔注射氯胺酮 5 0 μg ,D组 :对照组 ,神经结扎前 30min及术后 4d每天注入人工脑脊液。神经结扎术后第 7d ,所有动物腹腔内注射亚镇痛量的芬太尼 0 2 μg。自神经结扎术前 1d起至术后 10d每天观察大鼠热痛阈和自发痛行为的变化。结果 A、B两组痛行为均明显轻于D组 (P <0 0 5 ) ,且维持至停药后较长时间 ,C组用药后痛行为减轻 (P <0 0 5 ) ,但维持时间短 ,A、B两组较C、D两组能显著提高亚镇痛量芬太尼的镇痛作用 (P <0 0 5 )。A、B两组间无显著性差异 (P >0 0 5 )。结论 蛛网膜下腔应用氯胺酮可有效地防治神经痛 ,并加强亚镇痛量的芬太尼的镇痛作用。

Objective The present experiment was designed to investigate the effects of ketamine (a non competitive NMDA receptor antagonist) administered intrathecally on pain related behaviors in rats with painful peripheral mononeuropathy caused by chronic compression Methods Forty male SD rats weighing 230 260g were anesthetized with intraperitoneal 1% pentobarbital sodium 40mg/kg A plastic tube 0 5 mm in diameter was inserted into subarachnoid space with its tip reaching the enlargement and fixed One week after the implantation of the plastic catheter, sciatic nerve was exposed and four ties loose enough to permit blood flow on the neurolemma were placed around the sciatic nerve The rats were divided randomly into 4 groups with 10 rats each Group A: ketamine 5μg administered intrathecally 30 min before and on day 1,2,and 3 after sciatic nerve ligation Group B: ketamine 50μg was given intrathecally as in group A instead of 5μg Group C: ketamine 50μg administered intrathecally on 4th day after sciatic nerve ligation Group D: artificial cerebrospinal fluid administered intrathecally 30min before and daily for 4 days after sciatic nerve ligation The hyperalgesia to radiant heat and spontaneous nociceptive behaviors were assessed one day before and daily after nerve ligation On 7th day after nerve ligation subanalgesic dose fentanyl 0 2μg was injected intraperitoneally Results Pain related behaviors in group A and B reduced significantly compared with that in group D(P<0 05)and analgesia was maintained for a fairly long period of time after drug withdrawal In group C pain related behaviors also decreased significantly after ketamine administration(P<0 05), but analgesia was maintained only for a short period of time The antinociceptive effect of subanalgesic dose of fentanyl were enhanced significantly in group A and B as compared with that in group C and D(P<0 05) There was no significant difference between group A and B(P>0 05) Conclusions Ketamine administered intrathecally can prevent and treat neuropathic pain effectively and enhance the antinociceptive effect of fentanyl in subanalgesic dose