Topical transient receptor potential ankyrin 1 antagonist treatment attenuates nociception and inflammation in an ultraviolet B radiation-induced burn model in mice

Fialho, Maria Fernanda Pessano; Brum, Evelyne da Silva; Pegoraro, Natháli Schopf; Couto, Ana Claudia Gontijo; Trevisan, Gabriela; Cruz, Letícia; Oliveira, Sara Marchesan

doi:10.1016/j.jdermsci.2020.01.005

Cited by 10 publications

(6 citation statements)

References 40 publications

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“…TRPA1 is also involved in ultraviolet radiation-induced burn. In mice, topical administration of the TRPA1 antagonist, HC-030031, applied after irradiation blocked the development of mechanical and thermal allodynia 223 .…”

Section: Dermatology and Ophthalmologymentioning

confidence: 98%

Advances in TRP channel drug discovery: from target validation to clinical studies

Koivisto

Belvisi

Gaudet

et al. 2021

Nat Rev Drug Discov

293

171

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Transient receptor potential (TRP) channels are multifunctional signalling molecules with many roles in sensory perception and cellular physiology. Therefore, it is not surprising that TRP channels have been implicated in numerous diseases, including hereditary disorders caused by defects in genes encoding TRP channels (TRP channelopathies). Most TRP channels are located at the cell surface, which makes them generally accessible drug targets. Early drug discovery efforts to target TRP channels focused on pain, but as our knowledge of TRP channels and their role in health and disease has grown, these efforts have expanded into new clinical indications, ranging from respiratory disorders through neurological and psychiatric diseases to diabetes and cancer. In this Review, we discuss recent findings in TRP channel structural biology that can affect both drug development and clinical indications. We also discuss the clinical promise of novel TRP channel modulators, aimed at both established and emerging targets. Last, we address the challenges that these compounds may face in clinical practice, including the need for carefully targeted approaches to minimize potential side-effects due to the multifunctional roles of TRP channels.

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Section: Dermatology and Ophthalmologymentioning

confidence: 98%

Advances in TRP channel drug discovery: from target validation to clinical studies

Koivisto

Belvisi

Gaudet

et al. 2021

Nat Rev Drug Discov

293

171

View full text Add to dashboard Cite

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“…The polymodal TRP ion channels are expressed in many cell types including keratinocytes, melanocytes, sensory neurons, and immune cells in the skin where they function as cellular sensors in response to chemical and environmental stimuli. Besides the TRPV3 channel, other TRP channels, such as TRPV4, TRPA1, TRPV1, TRPM8, and TRPC7, have also been reported for their involvement in UV‐induced melanin formation and deposition, photoaging, and sunburn pain 14,30,44–48 . As a warmth‐sensitive channel, TRPV3 appears to play a critical role in UVB‐induced skin inflammation in comparison to other calcium permeable channels.…”

Section: Discussionmentioning

confidence: 99%

“…Besides the TRPV3 channel, other TRP channels, such as TRPV4, TRPA1, TRPV1, TRPM8, and TRPC7, have also been reported for their involvement in UV-induced melanin formation and deposition, photoaging, and sunburn pain. 14,30,[44][45][46][47][48] As a warmth-sensitive channel, TRPV3 appears to play a critical role in UVBinduced skin inflammation in comparison to other calcium permeable channels. Although other TRP channels are expressed, their expression levels are relatively low in comparison with TRPV3 that is robustly expressed in the keratinocytes that absorb the majority of ultraviolet radiation.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of cutaneous heat‐sensitive Ca²⁺‐permeable transient receptor potential vanilloid 3 channels alleviates UVB‐induced skin lesions in mice

Qu,

Sun,

Wei

et al. 2023

The FASEB Journal

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Ultraviolet B (UVB) radiation causes skin injury by trigging excessive calcium influx and signaling cascades in the skin keratinocytes. The heat‐sensitive Ca2+‐permeable transient receptor potential vanilloid 3 (TRPV3) channels robustly expressed in the keratinocytes play an important role in skin barrier formation and wound healing. Here, we report that inhibition of cutaneous TRPV3 alleviates UVB radiation‐induced skin lesions. In mouse models of ear swelling and dorsal skin injury induced by a single exposure of weak UVB radiation, TRPV3 genes and proteins were upregulated in quantitative real‐time PCR and Western blot assays. In accompany with TRPV3 upregulations, the expressions of proinflammatory cytokines tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) were also increased. Knockout of the TRPV3 gene alleviates UVB‐induced ear swelling and dorsal skin inflammation. Furthermore, topical applications of two selective TRPV3 inhibitors, osthole and verbascoside, resulted in a dose‐dependent attenuation of skin inflammation and lesions. Taken together, our findings demonstrate the causative role of overactive TRPV3 channel function in the development of UVB‐induced skin injury. Therefore, topical inhibition of TRPV3 may hold potential therapy or prevention of UVB radiation‐induced skin injury.

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“…This paper focuses mainly on topical treatments utilized in clinical practice. However, there are numerous preclinical trials pointing at the antinociceptive effect of substances administered topically in NP animal models, though they have not yet been introduced in clinical practice and are thus not included in this review [24,25].…”

mentioning

confidence: 99%

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

et al. 2021

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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.

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Topical transient receptor potential ankyrin 1 antagonist treatment attenuates nociception and inflammation in an ultraviolet B radiation-induced burn model in mice

Cited by 10 publications

References 40 publications

Advances in TRP channel drug discovery: from target validation to clinical studies

Advances in TRP channel drug discovery: from target validation to clinical studies

Inhibition of cutaneous heat‐sensitive Ca²⁺‐permeable transient receptor potential vanilloid 3 channels alleviates UVB‐induced skin lesions in mice

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

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Topical transient receptor potential ankyrin 1 antagonist treatment attenuates nociception and inflammation in an ultraviolet B radiation-induced burn model in mice

Cited by 10 publications

References 40 publications

Advances in TRP channel drug discovery: from target validation to clinical studies

Advances in TRP channel drug discovery: from target validation to clinical studies

Inhibition of cutaneous heat‐sensitive Ca2+‐permeable transient receptor potential vanilloid 3 channels alleviates UVB‐induced skin lesions in mice

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

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Resources

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Inhibition of cutaneous heat‐sensitive Ca²⁺‐permeable transient receptor potential vanilloid 3 channels alleviates UVB‐induced skin lesions in mice