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.

Molecular Mechanisms and Therapeutic Potential of Gabapentin with a Focus on Topical Formulations to Treat Ocular Surface Diseases

“…GBP was originally developed as an analgesic and, indeed GBP's efficacy for neuropathic pain and postherpetic neuralgia is well-established, with its use as monotherapy or adjunctive therapy supported by case reports and reviews [44]. GBP treatments have also shown efficacy in diabetic peripheral neuropathy [45]; postherpetic neuralgia (PHN) [46], trigeminal neuralgia [47]; neuropathic pain further to paclitaxel chemotherapy [48]; and cancer-related pain in pregnant patients [49]. Pain control in pediatric patients has also been described [50,51].…”

Molecular Mechanisms and Therapeutic Potential of Gabapentin with a Focus on Topical Formulations to Treat Ocular Surface Diseases

“…GBP was originally developed as an analgesic, and indeed GBP's efficacy for neuropathic pain and postherpetic neuralgia is well-established, with its use as monotherapy or adjunctive therapy supported by case reports and reviews [43]. GBP treatments have also shown efficacy in diabetic peripheral neuropathy [44]; postherpetic neuralgia (PHN) [45], trigeminal neuralgia [46]; neuropathic pain further to paclitaxel chemotherapy [47], and cancer-related pain in pregnant patients [48]. Pain control in pediatric patients has also been described [49,50].…”