使用8%辣椒素贴剂合理治疗化疗引起的周围神经病变：从缓解疼痛到改善病情

Rational treatment of chemotherapy-induced peripheral neuropathy with capsaicin 8% patch: from pain relief towards disease modification.

作者信息

Anand Praveen, Elsafa Enas, Privitera Rosario, Naidoo Kalnisha, Yiangou Yiangos, Donatien Philippe, Gabra Hani, Wasan Harpreet, Kenny Laura, Rahemtulla Amin, Misra Peter

机构信息

Department of Neurology.

Medical Oncology.

出版信息

J Pain Res. 2019 Jul 3;12:2039-2052. doi: 10.2147/JPR.S213912. eCollection 2019.

DOI:10.2147/JPR.S213912

PMID:31308732

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6613356/

Abstract

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; =0.02), touch-evoked pain (-1.823; =0.03) and cold-evoked pain (-1.456; =0.03). Short-Form McGill questionnaire showed a reduction in neuropathic (=0.0007), continuous (=0.01) and overall pain (=0.004); Patient Global Impression of Change showed improvement (=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, =0.009; heat receptor TRPV1, =0.027; regenerating nerve marker GAP43, =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.

摘要

目的

化疗引起的周围神经病变（CIPN）及相关慢性疼痛是一种常见且致残的病症。目前用于治疗CIPN神经性疼痛的方法大多无效，且有不良副作用。8%辣椒素贴剂（辣椒素179毫克贴剂）已被批准用于治疗神经性疼痛：单次局部皮肤给药可产生长达12周的有效疼痛缓解。我们评估了8%辣椒素贴剂对疼痛性CIPN患者的治疗潜力及其作用机制。

患者与方法

16例慢性疼痛性CIPN患者（平均病程2.5年），癌症已缓解且未接受化疗，将8%辣椒素贴剂敷于足部30分钟进行治疗。使用11点数字疼痛评分量表（NPRS）和问卷对症状进行监测。在基线和贴剂应用后三个月进行检查，包括用一系列标记物进行皮肤活检和定量感觉测试（QST）。

结果

患者报告自发疼痛（平均NPRS：-1.27；95%可信区间0.2409至2.301；P = 0.02）、触觉诱发疼痛（-1.823；P = 0.03）和冷觉诱发疼痛（-1.456；P = 0.03）显著减轻。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）减轻；患者总体变化印象显示有所改善（P = 0.001）。基线皮肤活检显示表皮内神经纤维（IENF）缺失，通过图像分析量化的表皮下神经纤维也缺失。贴剂应用后皮肤活检显示表皮内和表皮下神经纤维向正常化显著增加（对于IENF：结构标记物PGP9.5，P = 0.009；热受体TRPV1，P = 0.027；再生神经标记物GAP43，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恢复正常。与先前研究一样QST保持不变，且无全身副作用。