Efficacy of naltrexone on acetylcholine-induced alloknesis in atopic eczema
Efficacy of naltrexone on acetylcholine-induced alloknesis in atopic eczema
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DOI：
10.1034/j.1600-0625.2002.110508.x
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发表时间：
2002-10-01
影响因子：
3.6
通讯作者：
Martus, P
中科院分区：
文献类型：
--
作者：
Heyer, G;Groene, D;Martus, P
特应性湿疹是一种慢性湿疹性炎症性皮肤病。虽然引起和维持瘙痒的介质和确切机制尚不完全清楚，但临床试验中的AE患者已显示在吗啡拮抗剂治疗下获益。纳洛酮（NAL）是一种相对纯的吗啡拮抗剂，其阻断阿片类药物的作用是纳洛酮的两倍。NAL表现出最小的药理活性，并取代在μ-和κ-受体的内啡肽，而没有其自身的内在活性。NAL良好的口服生物利用度和血浆浓度-时间曲线下面积的线性增加使其成为实验研究的理想选择。我们设计了我们目前的实验类似于以前的实验评估外周皮肤感觉和中枢瘙痒过程，以获得更多的信息阿片受体的可能分布和参与瘙痒的病理生理。11例AE患者参加了我们的双盲研究。在乙酰胆碱（ACH）注射前60分钟给予参与者25 mg NAL（Nemexin（R））或安慰剂（PLA）[皮内（i.c.）注射0.02 ml 0.55 M]。用缓冲盐水的PLA刺激作为对侧前臂的对照。我们使用激光多普勒血流仪测量ACH注射后血管舒缩的变化，并使用视觉模拟量表（VAS）记录瘙痒的持续时间和强度。在评价风团和潮红感觉后，我们通过用刷子朝注射部位的向心方向轻轻抚摸周围皮肤，获得了注射部位周围的瘙痒皮肤区域（感觉异常）。对结果进行平面分析评价。口服NAL可显著减轻病灶周围瘙痒（P < 0.009）。在我们的四次观察中，变构区完全消失。瘙痒持续时间缩短20 s，瘙痒强度减弱，但不显著。NAL对激光多普勒测量的胆碱能血管反应无显著影响（P > 0.50），尤其不能降低血管反应改变的典型标志--初始流量反应（P > 0.25）。风团（P = 0.008）和潮红（P = 0.01）扩展的减少表明我们的治疗剂量适合本实验。NAL的最显着效果观察到的瘙痒处理参数，如变感（P = 0.009）和耀斑扩展（P = 0.01）。因此，我们赞成的概念，NAL可能有更强的影响中枢神经机制比外周伤害性结构。
Atopic eczema (AE) is a chronically pruritic inflammatory skin disease. Although the mediators and exact mechanisms eliciting and sustaining pruritus are not completely known, AE patients in clinical trials have been shown to benefit under treatment with morphine antagonists. Naltrexone (NAL) is a relatively pure morphine antagonist that blocks the effects of opioids twice as much as naloxone. NAL exhibits minimal pharmacological activity and displaces endorphines at mu- and kappa-receptors without its own intrinsic activity. NAL's excellent oral bioavailability and linear increases in the area under plasma concentration-time curve make it ideal for use in experimental studies. We designed our present experiments similar to former experiments evaluating both peripheral cutaneous sensations and central itch procession in order to gain more information about the possible distribution of opioid receptors and their involvement in the pathophysiology of pruritus. Eleven AE patients participated in our double-blind study. Either 25 mg of NAL (Nemexin(R)) or a placebo (PLA) was given to the participants 60 min prior to the acetylcholine (ACH) injection [intracutaneous (i.c.) injection of 0.02 ml of 0.55 M]. A PLA stimulus with buffered saline served as control on the opposite forearm. We used laser Doppler flowmetry to measure the vasomotoric changes after ACH injection and recorded the duration and intensity of itch with a visual analogue scale (VAS). Following the evaluation of wheal and flare sensation, we obtained the area of itchy skin around the injection site (alloknesis) by gently stroking the surrounding skin with a brush in the centripetal direction towards the injection site. The results were planimetrically evaluated. Oral NAL reduced the perifocal itch significantly (P < 0.009). In four of our observations the area of alloknesis completely disappeared. Itch duration was reduced by 20 s and the intensity of itch was diminished, yet not significantly. NAL had no significant effects on cholinergic vasoreactions measured by the laser Doppler (P > 0.50) and especially failed to decrease the initial flux response, which is a typical sign of an altered vascular reaction (P > 0.25). The decrease of wheal (P = 0.008) and flare (P = 0.01) extension indicates an appropriate dosage of our treatment for this experiment. The most significant effects of NAL were observed in parameters of itch processing such as alloknesis (P = 0.009) and flare extension (P = 0.01). Therefore we favour the concept that NAL might have a stronger impact on central nervous mechanisms than on peripheral nociceptive structures.