Mikkelsen S, Ilkjaer S, Brennum J, Borgbjerg F M, Dahl J B
Department of Anesthesiology, Copenhagen University Hospital, Herlev, Denmark.
Anesthesiology. 1999 Jun;90(6):1539-45. doi: 10.1097/00000542-199906000-00007.
The (NMDA) receptor plays a significant role in wind-up and spinal hypersensitivity and is involved in the occurrence of secondary hyperalgesia. Ketamine is an NMDA-receptor antagonist and has proven effective in alleviating secondary hyperalgesia in humans. Although it is disputed, the actions of ketamine have been ascribed not only to NMDA receptor antagonism, but also to opioid receptor agonism. A study therefore was designed in which the abolishment of a previously demonstrated effect of ketamine on secondary hyperalgesia was sought by pretreatment with naloxone.
Twenty-five volunteers were subjected to three treatment regimens. A standardized first-degree burn injury was induced. On appearance of primary and secondary hyperalgesia, one of the following infusion schemes was applied in a randomized, double-blind, cross-over fashion: (1) infusion of naloxone (0.8 mg/15 min followed by 0.4 mg/h), succeeded by infusion of ketamine (0.3 mg x kg(-1) x 15 min(-1) followed by 0.3 mg x kg(-1) x h(-1)); (2) infusion of placebo, succeeded by infusion of ketamine (0.3 mg x kg(-1) x 15 min(-1) followed by 0.3 mg x kg(-1) x h(-1)); and (3) infusion of placebo, succeeded by infusion of placebo. Heat-pain detection thresholds, magnitude of secondary hyperalgesia around the burn injury, and side effects were determined.
Ketamine reduced secondary hyperalgesia. Naloxone did not affect the action of ketamine. The magnitudes of side effects were equal if the subjects received ketamine, regardless of preceding infusion of naloxone.
In this experimental setting, opioid receptor blockade does not inhibit ketamine-induced reductions of secondary hyperalgesia.
N-甲基-D-天冬氨酸（NMDA）受体在痛觉过敏和脊髓超敏反应中起重要作用，并参与继发性痛觉过敏的发生。氯胺酮是一种NMDA受体拮抗剂，已被证明可有效减轻人类的继发性痛觉过敏。尽管存在争议，但氯胺酮的作用不仅归因于NMDA受体拮抗，还归因于阿片受体激动。因此，设计了一项研究，通过用纳洛酮预处理来寻求消除氯胺酮先前证明的对继发性痛觉过敏的作用。
25名志愿者接受了三种治疗方案。诱导标准化的一度烧伤。在原发性和继发性痛觉过敏出现时，以随机、双盲、交叉方式应用以下输注方案之一：（1）输注纳洛酮（0.8mg/15分钟，随后0.4mg/小时），接着输注氯胺酮（0.3mg·kg-1·15分钟-1，随后0.3mg·kg-1·小时-1）；（2）输注安慰剂，接着输注氯胺酮（0.3mg·kg-1·15分钟-1，随后0.3mg·kg-1·小时-1）；（3）输注安慰剂，接着输注安慰剂。测定热痛检测阈值、烧伤周围继发性痛觉过敏的程度和副作用。
氯胺酮减轻了继发性痛觉过敏。纳洛酮不影响氯胺酮的作用。如果受试者接受氯胺酮，无论之前是否输注纳洛酮，副作用的程度都是相同的。
在本实验环境中，阿片受体阻断并不抑制氯胺酮诱导的继发性痛觉过敏减轻。
