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Cutaneous targets for topical pain medications in patients with neuropathic pain: individual differential expression of biomarkers supports the need for personalized medicine.


ABSTRACT:

Introduction

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).

Objectives

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.

Methods

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.

Results

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.

Conclusion

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.

SUBMITTER: Albrecht PJ 

PROVIDER: S-EPMC10876238 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Cutaneous targets for topical pain medications in patients with neuropathic pain: individual differential expression of biomarkers supports the need for personalized medicine.

Albrecht Phillip J PJ   Liu Yi Y   Houk George G   Ruggiero Beth B   Banov Daniel D   Dockum Marilyn M   Day A J AJ   Rice Frank L FL   Bassani Gus G  

Pain reports 20240216 2


<h4>Introduction</h4>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).<h4>Objectives</h4>The study intended to identify  ...[more]

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