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Review

Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain—Narrative Review

1
Department of Pain Research and Treatment, Jagiellonian University Medical College, 31-008 Krakow, Poland
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Department of Interdisciplinary Intensive Care, Jagiellonian University Medical College, 31-008 Krakow, Poland
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Department of Pain Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, Poland
4
Institute for Neuropathic Pain, 1056 SN Amsterdam, The Netherlands
5
Department of Anesthesiology, Amsterdam University Medical Center, 1081 HV Amsterdam, The Netherlands
*
Authors to whom correspondence should be addressed.
Academic Editors: Wojciech Leppert and M. Begoña Delgado-Charro
Pharmaceutics 2021, 13(4), 450; https://doi.org/10.3390/pharmaceutics13040450
Received: 9 February 2021 / Revised: 17 March 2021 / Accepted: 22 March 2021 / Published: 26 March 2021
(This article belongs to the Special Issue Topical Drug Delivery in the Treatment of Pain)
Neuropathic pain in humans results from an injury or disease of the somatosensory nervous system at the peripheral or central level. Despite the considerable progress in pain management methods made to date, peripheral neuropathic pain significantly impacts patients’ quality of life, as pharmacological and non-pharmacological methods often fail or induce side effects. Topical treatments are gaining popularity in the management of peripheral neuropathic pain, due to excellent safety profiles and preferences. Moreover, topical treatments applied locally may target the underlying mechanisms of peripheral sensitization and pain. Recent studies showed that peripheral sensitization results from interactions between neuronal and non-neuronal cells, with numerous signaling molecules and molecular/cellular targets involved. This narrative review discusses the molecular/cellular mechanisms of drugs available in topical formulations utilized in clinical practice and their effectiveness in clinical studies in patients with peripheral neuropathic pain. We searched PubMed for papers published from 1 January 1995 to 30 November 2020. The key search phrases for identifying potentially relevant articles were “topical AND pain”, “topical AND neuropathic”, “topical AND treatment”, “topical AND mechanism”, “peripheral neuropathic”, and “mechanism”. The result of our search was 23 randomized controlled trials (RCT), 9 open-label studies, 16 retrospective studies, 20 case (series) reports, 8 systematic reviews, 66 narrative reviews, and 140 experimental studies. The data from preclinical studies revealed that active compounds of topical treatments exert multiple mechanisms of action, directly or indirectly modulating ion channels, receptors, proteins, and enzymes expressed by neuronal and non-neuronal cells, and thus contributing to antinociception. However, which mechanisms and the extent to which the mechanisms contribute to pain relief observed in humans remain unclear. The evidence from RCTs and reviews supports 5% lidocaine patches, 8% capsaicin patches, and botulinum toxin A injections as effective treatments in patients with peripheral neuropathic pain. In turn, single RCTs support evidence of doxepin, funapide, diclofenac, baclofen, clonidine, loperamide, and cannabidiol in neuropathic pain states. Topical administration of phenytoin, ambroxol, and prazosin is supported by observational clinical studies. For topical amitriptyline, menthol, and gabapentin, evidence comes from case reports and case series. For topical ketamine and baclofen, data supporting their effectiveness are provided by both single RCTs and case series. The discussed data from clinical studies and observations support the usefulness of topical treatments in neuropathic pain management. This review may help clinicians in making decisions regarding whether and which topical treatment may be a beneficial option, particularly in frail patients not tolerating systemic pharmacotherapy. View Full-Text
Keywords: localized neuropathic pain; ion channels; receptors; peripheral mechanisms; topical treatment; peripheral sensitization; lidocaine; capsaicin; BTX-A; polyneuropathy; peripheral neuropathic pain localized neuropathic pain; ion channels; receptors; peripheral mechanisms; topical treatment; peripheral sensitization; lidocaine; capsaicin; BTX-A; polyneuropathy; peripheral neuropathic pain
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MDPI and ACS Style

Kocot-Kępska, M.; Zajączkowska, R.; Mika, J.; Kopsky, D.J.; Wordliczek, J.; Dobrogowski, J.; Przeklasa-Muszyńska, A. Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain—Narrative Review. Pharmaceutics 2021, 13, 450. https://doi.org/10.3390/pharmaceutics13040450

AMA Style

Kocot-Kępska M, Zajączkowska R, Mika J, Kopsky DJ, Wordliczek J, Dobrogowski J, Przeklasa-Muszyńska A. Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain—Narrative Review. Pharmaceutics. 2021; 13(4):450. https://doi.org/10.3390/pharmaceutics13040450

Chicago/Turabian Style

Kocot-Kępska, Magdalena, Renata Zajączkowska, Joanna Mika, David J. Kopsky, Jerzy Wordliczek, Jan Dobrogowski, and Anna Przeklasa-Muszyńska. 2021. "Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain—Narrative Review" Pharmaceutics 13, no. 4: 450. https://doi.org/10.3390/pharmaceutics13040450

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