Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain
Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain
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DOI：
10.1016/s0304-3959(00)00433-4
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发表时间：
2001-03-01
期刊：
影响因子：
7.4
通讯作者：
Yaksh, T
中科院分区：
文献类型：
--
作者：
Leung, A;Wallace, MS;Yaksh, T
在神经损伤后临床前疼痛模型中，mu阿片受体激动剂和n -甲基- d -天冬氨酸（NMDA）受体拮抗剂均参与神经性疼痛的调节。本研究描述了静脉输注阿芬太尼（一种mu受体激动剂）和氯胺酮（一种nmda受体拮抗剂）对人类神经性疼痛状态的影响，其特征是异常性疼痛和痛觉过敏。以苯海拉明作为安慰剂，通过计算机控制输注（CCI）泵以随机双盲方式间隔1周输注阿芬太尼和氯胺酮，计算机控制输注泵将阿芬太尼的血浆水平设定为25、50和75 ng/ml，氯胺酮的血浆水平设定为50、100和150 ng/ml。在每次输注开始时和每次目标血浆水平时，获得基线生命体征，包括热阈值，热痛和von Frey纤维阈值在内的神经感觉测试以及自发和诱发性疼痛评分。此外，在每次输注开始和结束时绘制对抚摸和5.18 von Frey细丝的异常性疼痛或痛觉过敏区域。共有7名男性和5名女性神经损伤后异常性疼痛和痛觉过敏被纳入研究。注意到冷、热、热痛和von Frey触觉阈值的升高。在阿芬太尼和氯胺酮输注中，冷痛阈值和冷痛阈值的剂量依赖性增加，以及卒中疼痛评分的降低都被注意到。此外，阿芬太尼在自发性疼痛和von Frey疼痛评分中均显示出具有统计学意义的剂量依赖性降低。阿芬太尼和氯胺酮输注均显示中风性痛觉过敏区域减少，氯胺酮显示von Frey痛觉过敏区域显著减少。未见明显中枢神经系统副作用及生命体征改变。神经损伤后出现异常性疼痛和痛觉过敏的患者存在部分神经传递障碍。阿芬太尼对冷痛阈值和自发性疼痛评分的影响与先前的研究表明阿片类中枢镇痛作用相关。此外，阿芬太尼输注后痛觉面积和诱发疼痛评分的减少表明阿片类药物可能对神经损伤后患者有一定的外周作用。因此，临床使用阿片类药物谨慎滴定可能有利于神经损伤后部分神经传递障碍患者。氯胺酮输注在没有明显中枢神经系统副作用的情况下，不仅证明了已有文献记载的NMDA受体的脊髓机制，而且本研究结果还提示NMDA受体可能存在外周机制。中枢致敏与外周nmda受体表达调节之间的关系有待进一步研究。(C) 2001国际疼痛研究协会。Elsevier Science B.V.版权所有
Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a mu -receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a randomized double-blind fashion 1 week apart via a computer-controlled infusion (CCI) pump that was programmed to target plasma levels of alfentanil at 25, 50 and 75 ng/ml and ketamine at 50, 100 and 150 ng/ml. At the beginning of each infusion and each targeted plasma level, baseline vital signs, neurosensory testing that included thermal thresholds, thermal pain and von Frey filament thresholds, and spontaneous and evoked pain scores were obtained. Moreover, the areas of allodynia or hyperalgesia to stroking and a 5.18 von Frey filament were mapped at the beginning and the end of each infusion. A total of seven males and five females with post-nerve injury allodynia and hyperalgesia were enrolled in the study. Elevations of cold, warm, hot pain and von Frey tactile thresholds were noted. Dose-dependent increases in cold and cold pain thresholds, and reductions in stroking pain scores were noted in both the alfentanil and the ketamine infusions. In addition, alfentanil showed a statistically significant dose-dependent reduction in both spontaneous and von Frey pain scores. Both the alfentanil and ketamine infusions showed a reduction in the stroking hyperalgesic area and ketamine showed a significant reduction in the von Frey hyperalgesia area. No significant CNS side effects and changes in vital signs were noted. A partial deafferentation state was found in the post-nerve injury patients who presented with allodynia and hyperalgesia. The effects of alfentanil on cold and cold pain thresholds and spontaneous pain scores correlates with previous studies suggesting an opiate central analgesic effect. In addition, the reduction of the hyperalgesic area and evoked pain scores with the alfentanil infusion suggests that opioids may have some peripheral effects in the post-nerve injury patients. Therefore, clinical utilization of opioids with careful titration may be beneficial in post-nerve injury patients with partial deafferentation. With the absence of significant CNS side effects, the ketamine infusion not only demonstrated the well-documented spinal cord mechanism of the NMDA receptor, but the result of the current study also suggests that a peripheral mechanism of NMDA receptor may exist. The relationship between central sensitization and regulation of peripheral NMDA-receptor expression requires further investigation. (C) 2001 International Association for the Study of Pain. published by Elsevier Science B.V. All rights reserved.