Treatment of pruritus with topically applied opiate receptor antagonist
Treatment of pruritus with topically applied opiate receptor antagonist
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DOI：
10.1016/j.jaad.2007.01.007
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发表时间：
2007-06-01
影响因子：
13.8
通讯作者：
Bigliardi-Qi, Mei
中科院分区：
文献类型：
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作者：
Bigliardi, Paul L.;Stammer, Holger;Bigliardi-Qi, Mei
背景：瘙痒是最常见和令人痛苦的皮肤症状，瘙痒的治疗是成千上万人的问题。目前可用的治疗方法不是很有效。因此，迫切需要寻找新的有效的局部药物来治疗瘙痒。我们进行了两项独立的研究，以评估局部应用纳洛酮，阿片受体拮抗剂，在治疗严重瘙痒症的疗效。第一项开放性研究的目的是将局部应用纳洛酮治疗不同皮炎皮肤疾病的临床疗效与表皮p-阿片受体（莫尔）表达的变化相关联。第二项研究是一个双盲，安慰剂对照，交叉研究瘙痒症的特应性dermatitis.Methods：最初，我们进行了一个开放的试点研究18例不同的慢性皮炎疾病使用局部制剂的1%纳洛酮2周。11例患者在使用纳曲酮乳膏前后进行穿刺活检，并测量表皮莫尔染色。随后，用相同的制剂进行随机、安慰剂对照、交叉试验。在这项试验中，我们包括40例局部和全身性特应性皮炎与严重trustry.Results：在开放研究超过70%的患者使用1%纳洛酮霜经历了显着减少瘙痒。更有趣的是，用纳洛酮局部治疗引起表皮莫尔染色增加。表皮阿片受体的调节与临床评估相关。安慰剂对照的交叉试验清楚地表明，与安慰剂相比，含有纳洛酮的乳膏的总体效果好29.4%。含有纳洛酮的制剂需要46分钟的中位数，以减少瘙痒症状的50%，安慰剂，74 minutes.Limitations：我们只能在11例活检标本，这意味着一个令人满意的统计分析表皮莫尔染色的变化是不可能的。此外，肾源性瘙痒症和银屑病患者的数量不足，以得出明确的结论。结论：安慰剂对照研究显示，局部应用纳洛酮的安慰剂制剂的显着优势。这一发现得到了开放性研究的活检结果的支持，显示了局部纳洛酮治疗后表皮中莫尔表达的调节，特别是在特应性皮炎中。这些结果清楚地表明局部应用阿片受体拮抗剂治疗瘙痒症的潜力。安慰剂制剂也有一定的抗过敏作用。这强调了皮肤干燥的再水化治疗在瘙痒症治疗中的重要性。
Background: Pruritus is the most common and distressing skin symptom, and treatment of itch is a problem for thousands of people. The currently available therapies are not very effective. Therefore there is an urgent need to find new effective topical drugs against itching.Objective. We conducted two separate studies to evaluate the efficacy of topically applied naltrexone, an opioid receptor antagonist, in the treatment of severe pruritus. The objective of the first open study was to correlate the clinical efficacy of topically applied naltrexone in different pruritic skin disorders to a change of epidermal p-opiate receptor (MOR) expression. The second study was a double-blind, placebo-controlled, crossover study on pruritus in atopic dermatitis.Methods: Initially we performed an open pilot study on 18 patients with different chronic pruritic disorders using a topical formulation of 1% naltrexone for 2 weeks. A punch biopsy was performed in 11 patients before and after the application of the naltrexone cream and the staining of epidermal MOR was measured. Subsequently, a randomized, placebo-controlled, crossover trial was performed with the same formulation. We included in this trial 40 patients with localized and generalized atopic dermatitis with severe pruritus.Results: In the open study more than 70% of the patients using the 1% naltrexone cream experienced a significant reduction of pruritus. More interestingly, the topical treatment with naltrexone caused an increase of epidermal MOR staining. The regulation of the epidermal opioid receptor correlated with the clinical assessment. The placebo-controlled, crossover trial demonstrated clearly that the cream containing naltrexone had an overall 29.4% better effect compared with placebo. The formulation containing naltrexone required a median of 46 minutes to reduce the itch symptoms to 50%; the placebo, 74 minutes.Limitations: We could only take biopsy specimens in 11 patients, which means that a satisfactory statistical analysis of the changes of epidermal MOR staining was not possible. In addition, there was an insufficient number of patients with nephrogenic pruritus and pruritic psoriasis to draw definitive conclusions.Conclusions: The placebo-controlled study showed a significant advantage of topically applied naltrexone over the placebo formulation. This finding is supported by the biopsy results from the open studies, showing a regulation of MOR expression in epidermis after treatment with topical naltrexone, especially in atopic dermatitis. These results clearly show potential for topically applied opioid receptor antagonist in the treatment of pruritus. The placebo formulation also had some antipruritic effects. This underlines the importance of rehydration therapy for dry skin in the treatment of pruritus.