Bromage P R, Camporesi E M, Durant P A, Nielsen C H
Anesthesiology. 1982 Jun;56(6):431-6. doi: 10.1097/00000542-198206000-00004.
Ten healthy males between 18 and 33 years received 10 mg morphine sulfate intravenously, or by lumbar epidural injection at two sessions 2-4 weeks apart, in random sequence. The following observations were made at intervals for 22 h. (1) Segmental hypalgesia to ice and pin scratch. (2) Cold pressor response test in hand and foot as an index of analgesia. (3) Time of onset and duration of side effects. (4) Serum concentrations of morphine. Few non-respiratory changes were seen after intravenous morphine. Cold pressor response was unchanged in hand and foot, no segmental hypalgesia or itching occurred, and only one subject complained of nausea. Marked changes occurred after epidural morphine. Cutaneous hypalgesia to ice and pin scratch appeared in the thoracolumbar region all subjects. In six subjects hypalgesia rose to the midthoracic region during the second or third hour and to the trigeminal distribution between the sixth and ninth hour in five subjects. Cold pressor response fell rapidly in the foot during the first 1.5 h after epidural morphine, and a little later cold pressor response also fell in the hand in all subjects, and remained depressed for the duration of the experimental period. Pruritus occurred at three hours in nine of the 10 subjects, nausea at about four hours in six of the subjects, and vomiting at about six hours in five of the subjects. Hypalgesia and side effects were not related to serum concentrations of morphine. These results suggest that lumbar epidural morphine travels cephalad in the cerebrospinal fluid to reach the brain stem and fourth ventricle by the sixth hour.
10名年龄在18至33岁之间的健康男性，在间隔2至4周的两个时段，以随机顺序接受了10毫克硫酸吗啡静脉注射或腰椎硬膜外注射。在22小时内定期进行以下观察：(1) 对冰敷和针刺划擦的节段性痛觉减退。(2) 以手足冷加压反应试验作为镇痛指标。(3) 副作用的起效时间和持续时间。(4) 吗啡的血清浓度。静脉注射吗啡后几乎未见非呼吸性变化。手足的冷加压反应未改变，未出现节段性痛觉减退或瘙痒，只有一名受试者主诉恶心。硬膜外注射吗啡后出现明显变化。所有受试者胸腰段均出现对冰敷和针刺划擦的皮肤痛觉减退。6名受试者在第二或第三小时痛觉减退升至胸中部，5名受试者在第六至第九小时痛觉减退升至三叉神经分布区。硬膜外注射吗啡后，足部冷加压反应在最初1.5小时内迅速下降，随后不久所有受试者手部的冷加压反应也下降，并在实验期内持续降低。10名受试者中有9名在3小时出现瘙痒，6名受试者在约4小时出现恶心，5名受试者在约6小时出现呕吐。痛觉减退和副作用与吗啡的血清浓度无关。这些结果表明，腰椎硬膜外注射的吗啡在脑脊液中向头端移动，到第六小时到达脑干和第四脑室。
