Pöyhiä Reino, Vainio Anneli
Department of Anaesthesia and Intensive Care, Helsinki University Central Hospital, Helsinki, Finland.
Clin J Pain. 2006 Jan;22(1):32-6. doi: 10.1097/01.ajp.0000149800.39240.95.
The n-methyl-d-aspartate receptor antagonists such as ketamine relieve chronic pain but their oral and parenteral use is limited by the adverse effects. Experimental studies indicate that the peripheral n-methyl-d-aspartate receptors are involved in nociception. Recent clinical findings suggest that ketamine gel alleviates neuropathic pain, but no placebo-controlled randomized studies are available on the neurosensory effects of ketamine gel in experimental neurogenic pain.
The aim of this study was to assess the effects of topically applied ketamine using the intradermal capsaicin model in healthy volunteers.
Nine healthy subjects received ketamine and placebo gel on 3 occasions in a randomized, double-blind, and crossover manner. The concentration of ketamine was 50 mg/mL. One milliliter of gel was rubbed into the skin of both forearms 10 minutes before the intradermal injection of capsaicin (250 microg). Thereafter, the intensity and unpleasantness of spontaneous and evoked pain and dysesthesia was assessed up to 60 minutes using a 10-cm visual analog scale. Pain and dysesthesia were evoked using cotton gauze, a von Frey microfilament, and 38 degrees C, 42 degrees C, and 47 degrees C heat. Side effects were recorded, and individuals' subjective experiences were assessed with a standard questionnaire.
Ketamine gel had no effect on immediate burning pain followed by the capsaicin injection. Both the intensity and unpleasantness of mechanical hyperalgesia was statistically significantly reduced by ketamine gel applied both on the left and right side. Neither tactile allodynia evoked by a brush nor thermal hyperalgesia were observed in any volunteer. No local or systemic side effects were observed. No patient reported any drug effects.
A significant reduction of mechanical hyperalgesia was produced by topically and pre-emptively applied ketamine in healthy patients. We propose that the mechanism of action would be the reduction of central sensitization caused by the absorption of ketamine in circulation.
氯胺酮等N-甲基-D-天冬氨酸受体拮抗剂可缓解慢性疼痛，但其口服和胃肠外用药会受到副作用的限制。实验研究表明，外周N-甲基-D-天冬氨酸受体参与痛觉形成。近期临床研究结果提示，氯胺酮凝胶可缓解神经性疼痛，但尚无关于氯胺酮凝胶对实验性神经源性疼痛神经感觉作用的安慰剂对照随机研究。
本研究旨在采用皮内注射辣椒素模型评估局部应用氯胺酮对健康志愿者的影响。
9名健康受试者以随机、双盲、交叉方式分3次接受氯胺酮和安慰剂凝胶。氯胺酮浓度为50mg/mL。在皮内注射辣椒素（250μg）前10分钟，将1mL凝胶涂抹于双侧前臂皮肤。此后，使用10厘米视觉模拟量表评估长达60分钟的自发痛、诱发性疼痛和感觉异常的强度及不适感。使用棉纱布、von Frey微丝以及38℃、42℃和47℃热刺激诱发疼痛和感觉异常。记录副作用，并使用标准问卷评估个体主观体验。
氯胺酮凝胶对辣椒素注射后的即刻灼痛无影响。氯胺酮凝胶应用于左侧和右侧均能使机械性痛觉过敏的强度和不适感在统计学上显著降低。在任何志愿者中均未观察到刷擦诱发的触觉异常性疼痛或热痛觉过敏。未观察到局部或全身副作用。无患者报告任何药物效应。
局部预先应用氯胺酮可使健康患者的机械性痛觉过敏显著减轻。我们认为其作用机制可能是循环中吸收的氯胺酮减少了中枢敏化。
