Study of morphine tolerance at spinal level-approach to spinal plasticity-

雄性SD大鼠腰段鞘内置管。鞘内注射吗啡20μg/10μ，L，每日2次，连续5天。为测量大鼠对伤害性刺激的戒断反应，对大鼠足爪进行辐射加热(RH)和爪压(PP)。用Semmes-Weinstein单丝(SWM)测量对非伤害性刺激的阈值。慢性吗啡给药增加对伤害性和非伤害性刺激的反应，提示脊髓敏化。第二项研究旨在探讨NMDA受体拮抗剂氯胺酮对慢性吗啡治疗所致过敏状态的影响。吗啡配伍/不配伍氯胺酮，每日2次，连续5天。联合应用氯胺酮可降低吗啡诱发的超敏反应，提示NMDA受体激活参与了慢性吗啡致脊髓敏化。3.研究利多卡因预处理对慢性吗啡诱发的脊髓超敏反应的影响。吗啡注射前10min注射利多卡因组与单纯注射吗啡组比较。利多卡因预处理不影响大鼠对伤害性刺激和非伤害性刺激的超敏反应，测量结束后，处死大鼠，取脊髓进行电生理研究。在MED探头上放置一片脊髓以记录电反应。生理盐水组和吗啡组之间的神经元活动很难进行精确的比较，因为切片的脊髓记录很差。

Male Sprague-Dawley rats were implanted lumber intrathecal catheters. Intrathecal injection of morphine 20 μg /10μl was repeated twice a day for 5 days. To measure withdrawal responses to noxious stimuli, radiant heating (RH) and paw pressure (PP) were applied to rat's paws. The threshold to non-noxious stimulus was measured using Semmes-Weinstein monofilament (SWM). Chronic morphine administration increased the responses to noxious and non-noxious stimuli, suggesting the spinal sensitization.Second study was designed to investigate the effect of ketamine, an NMDA receptor antagonist, on hypersensitive state induced by chronic morphine treatment. Morphine with/without ketamine was administered two times a day for 5 days. Combined ketamine reduced the hypersensitive state induced by morphine, suggesting that the NMDA receptor activation was involved in the spinal sensitization induced by chronic morphine.Third study was designed to investigate the effect of pretreatment of lidocaine to the hypersensitive responses induced by chronic morphine. The group injected lidocaine 10min before the morphine was compared to the group injected morphine alone. The pretreatment of lidocaine did not affect the hypersensitive responses to noxious and non-noxious stimuli.After the final measurement, rats were euthanized and taken spinal cords for electrophysiological study. A sliced spinal cord was placed on the MED probe for recording electric responses. It was difficult to compare the neuronal activities precisely between saline and morphine treated group, because of the poor recording from a sliced spinal cord.