Gilron I, Coderre T J
Department of Anaesthesia, McGill University, Montreal, Canada.
Anesthesiology. 1996 Mar;84(3):572-9. doi: 10.1097/00000542-199603000-00013.
The role of preemptive treatment with volatile and intravenous anesthetics has been examined in previous studies using the rat formalin test. Evidence describing analgesic properties of the gamma-amino butyric acid-ergic (GABAergic) steroid anesthetics, such as alphaxalone, suggest that they may suppress the development of central sensitization to pain. This study examined the preemptive effects of phaxalone in comparison with other GABAergic anesthetics, propofol and pentobarbital.
The pain behavior of rats was evaluated (using the previously validated weighted scores method of behavioral rating) 15-60 min after subcutaneous hind paw injection of 50 microg 1.5% formalin. In each trial, anesthetics and their respective vehicles were administered by tail-vein injection either 0.5-10 min before or 5 min after, formalin injection. When analgesic effects were observed with any of these agents, further studies were conducted with a GABA(A) receptor antagonist in an attempt to confirm a specific receptor-mediated action of the agent.
Alphaxalone pretreatment produced transient analgesia in the early part of phase 2, which was not observed in rats posttreated with alphaxalone. The analgesic effect of alphaxalone was antagonized by picrotoxin, as well. Neither pentobarbital nor propofol showed any analgesic effects at the doses used in our study.
Whereas alphaxalone was shown to produce preemptive analgesia through its action at the GABA(A) receptor, pentobarbital and propofol, which also are known to act at this site, showed no analgesic effects. The diversity of receptor subtypes and functional complexity of GABA(A) receptors is such that steroid anesthetics may have effects that are different from other GABAergic agents. Further research into the role of progesterone metabolites and steroid anesthetics in the prevention of central sensitization may have clinical implications for the treatment of acute or chronic pain.
在先前使用大鼠福尔马林试验的研究中，已对挥发性和静脉麻醉剂的超前镇痛作用进行了研究。描述γ-氨基丁酸能（GABA能）类固醇麻醉剂（如alphaxalone）镇痛特性的证据表明，它们可能抑制对疼痛的中枢敏化的发展。本研究比较了alphaxalone与其他GABA能麻醉剂丙泊酚和戊巴比妥的超前镇痛作用。
在大鼠后爪皮下注射50微克1.5%福尔马林后15 - 60分钟，评估大鼠的疼痛行为（使用先前验证的行为评分加权分数法）。在每次试验中，麻醉剂及其相应的溶媒通过尾静脉注射，在福尔马林注射前0.5 - 10分钟或注射后5分钟给药。当观察到这些药物中的任何一种有镇痛作用时，使用GABA(A)受体拮抗剂进行进一步研究，以试图证实该药物的特异性受体介导作用。
alphaxalone预处理在第2阶段早期产生了短暂的镇痛作用，而在接受alphaxalone后处理的大鼠中未观察到这种作用。alphaxalone的镇痛作用也被印防己毒素拮抗。在我们研究中使用的剂量下，戊巴比妥和丙泊酚均未显示出任何镇痛作用。
虽然alphaxalone通过作用于GABA(A)受体产生超前镇痛作用，但同样已知作用于该位点的戊巴比妥和丙泊酚却未显示出镇痛作用。GABA(A)受体亚型的多样性和功能复杂性使得类固醇麻醉剂可能具有与其他GABA能药物不同的作用。对孕酮代谢产物和类固醇麻醉剂在预防中枢敏化中的作用进行进一步研究可能对急性或慢性疼痛的治疗具有临床意义。
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