Albrecht Phillip J, Liu Yi, Houk George, Ruggiero Beth, Banov Daniel, Dockum Marilyn, Day A J, Rice Frank L, Bassani Gus
Integrated Tissue Dynamics, LLC (INTiDYN), Rensselaer, NY, USA.
Professional Compounding Centers of America (PCCA), Houston, TX, USA.
Pain Rep. 2024 Feb 16;9(2):e1119. doi: 10.1097/PR9.0000000000001121. eCollection 2024 Apr.
Numerous potential cutaneous targets exist for treating chronic pain with topically applied active pharmaceutical ingredients. This preliminary human skin tissue investigation was undertaken to characterize several key biomarkers in keratinocytes and provide proof-of-principle data to support clinical development of topical compounded formulations for peripheral neuropathic pain syndromes, such as postherpetic neuralgia (PHN).
The study intended to identify objective biomarkers in PHN skin on a patient-by-patient personalized medicine platform. The totality of biopsy biomarker data can provide a tissue basis for directing individualized compounded topical preparations to optimize treatment efficacy.
Referencing 5 of the most common actives used in topical pain relief formulations (ketamine, gabapentin, clonidine, baclofen, and lidocaine), and 3 well-established cutaneous mediators (ie, neuropeptides, cannabinoids, and vanilloids), comprehensive immunolabeling was used to quantify receptor biomarkers in skin biopsy samples taken from ipsilateral (pain) and contralateral (nonpain) dermatomes of patients with PHN.
Epidermal keratinocyte labeling patterns were significantly different among the cohort for each biomarker, consistent with potential mechanisms of action among keratinocytes. Importantly, the total biomarker panel indicates that the enriched PHN cohort contains distinct subgroups.
The heterogeneity of the cohort differences may explain studies that have not shown statistical group benefit from topically administered compounded therapies. Rather, the essential need for individual tissue biomarker evaluations is evident, particularly as a means to direct a more accurately targeted topical personalized medicine approach and generate positive clinical results.
使用局部应用的活性药物成分治疗慢性疼痛存在众多潜在的皮肤靶点。开展这项初步的人体皮肤组织研究，旨在表征角质形成细胞中的几种关键生物标志物，并提供原理验证数据，以支持用于外周神经病理性疼痛综合征（如带状疱疹后神经痛，PHN）的局部复方制剂的临床开发。
该研究旨在在患者个体化医学平台上识别PHN皮肤中的客观生物标志物。活检生物标志物数据的总体情况可为指导个体化复方局部制剂以优化治疗效果提供组织基础。
参考局部止痛制剂中最常用的5种活性成分（氯胺酮、加巴喷丁、可乐定、巴氯芬和利多卡因）以及3种已确定的皮肤介质（即神经肽、大麻素和香草酸类），采用全面免疫标记法对取自PHN患者同侧（疼痛）和对侧（非疼痛）皮节的皮肤活检样本中的受体生物标志物进行定量分析。
每个生物标志物在队列中的表皮角质形成细胞标记模式存在显著差异，这与角质形成细胞之间潜在的作用机制一致。重要的是，整个生物标志物组表明，富集的PHN队列包含不同的亚组。
队列差异的异质性可能解释了一些研究中未显示局部应用复方疗法具有统计学上的组间益处的原因。相反，显然迫切需要进行个体组织生物标志物评估，特别是作为一种指导更精准靶向的局部个体化药物治疗方法并产生积极临床结果的手段。
