Rational treatment of chemotherapy-induced peripheral neuropathy with capsaicin 8% patch: from pain relief towards disease modification
Rational treatment of chemotherapy-induced peripheral neuropathy with capsaicin 8% patch: from pain relief towards disease modification
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DOI：
10.2147/jpr.s213912
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发表时间：
2019-01-01
影响因子：
2.7
通讯作者：
Misra, Peter
中科院分区：
文献类型：
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作者：
Anand, Praveen;Elsafa, Enas;Misra, Peter
目的：化疗引起的周围神经病变（CIPN）伴慢性疼痛是一种常见的致残性疾病。目前对CIPN中神经性疼痛的治疗在很大程度上是无效的，具有不利的副作用。辣椒素8%贴剂（辣椒素179 mg贴剂）被批准用于治疗神经性疼痛：单次局部皮肤应用可有效缓解疼痛长达12周。我们评估了辣椒素8%补丁疼痛CIPN患者的治疗潜力，其mechanism of action.Patients和方法：16例慢性疼痛CIPN（平均持续时间2.5年），在缓解癌症和不接受化疗，用30分钟的辣椒素8%补丁应用到脚治疗。使用11分数字疼痛评级量表（NPRS）和问卷来监测症状。在基线和贴片应用后三个月进行调查，包括皮肤活检和一系列标记物，以及定量感觉测试（QST）。（平均NPRS：-1.27; 95% CI 0.2409至2.301; p=0.02）、触摸诱发疼痛（-1.823; p=0.03）和冷诱发疼痛（-1.456; p=0.03）。简式麦吉尔问卷显示神经性疼痛（p=0.0007）、持续性疼痛（p=0.01）和总体疼痛（p=0.004）减少;患者总体印象变化显示改善（p=0.001）。基线皮肤活检显示表皮内神经纤维（IENF）的损失，以及通过图像分析定量的表皮下神经纤维的损失。贴剂贴敷后皮肤活检显示表皮内和表皮下神经纤维的正常化显著增加（对于IENF：结构标志物PGP 9.5，p=0.009;热受体TRPV 1，p=0.027;再生神经标志物GAP 43，p=0.04）。神经生长因子（NGF）、神经营养因子-3（NT-3）和朗格汉斯细胞的表皮水平也正常化。QST保持不变，有没有全身副作用，在以前的studies.Conclusion：辣椒素8%补丁提供了显着的疼痛缓解CIPN，并可能导致再生和恢复的感觉神经纤维，即疾病的修改。
Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) with associated chronic pain is a common and disabling condition. Current treatments for neuropathic pain in CIPN are largely ineffective, with unfavorable side-effects. The capsaicin 8% patch (capsaicin 179 mg patch) is approved for the treatment of neuropathic pain: a single topical cutaneous application can produce effective pain relief for up to 12 weeks. We assessed the therapeutic potential of capsaicin 8% patch in patients with painful CIPN, and its mechanism of action.Patients and methods: 16 patients with chronic painful CIPN (mean duration 2.5 years), in remission for cancer and not receiving chemotherapy, were treated with 30 min application of capsaicin 8% patch to the feet. Symptoms were monitored using the 11-point numerical pain rating scale (NPRS), and questionnaires. Investigations were performed at baseline and three months after patch application, including skin biopsies with a range of markers, and quantitative sensory testing (QST).Results: Patients reported significant reduction in spontaneous pain (mean NPRS: -1.27; 95% CI 0.2409 to 2.301; p=0.02), touch-evoked pain (-1.823; p=0.03) and cold-evoked pain (-1.456; p=0.03). Short-Form McGill questionnaire showed a reduction in neuropathic (p=0.0007), continuous (p=0.01) and overall pain (p=0.004); Patient Global Impression of Change showed improvement (p=0.001). Baseline skin biopsies showed loss of intra-epidermal nerve fibers (IENF), and also of sub-epidermal nerve fibers quantified by image analysis. Post-patch application skin biopsies showed a significant increase towards normalization of intra-epidermal and sub-epidermal nerve fibers (for IENF: structural marker PGP9.5, p=0.009; heat receptor TRPV1, p=0.027; regenerating nerve marker GAP43, p=0.04). Epidermal levels of Nerve Growth Factor (NGF), Neurotrophin-3 (NT-3), and Langerhans cells were also normalized. QST remained unchanged and there were no systemic side-effects, as in previous studies.Conclusion: Capsaicin 8% patch provides significant pain relief in CIPN, and may lead to regeneration and restoration of sensory nerve fibers ie, disease modification.