Transient Receptor Potential Channels and Itch

Mahmoud, Omar; Soares, Georgia Biazus; Yosipovitch, Gil

doi:10.3390/ijms24010420

Cited by 24 publications

(20 citation statements)

References 63 publications

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“…It has been found that many other factors, including mast cell mediators, neuropeptides, neurotrophins, and proteases have many effects on the skin, mainly participating in the occurrence and development of itching [ 42 ]. Although the exact mechanism of itch has not been fully elucidated, it is clear that a complex crosstalk between the stratum corneum, keratinocytes, T cells, eosinophils, basophils, mast cells, and nerve fibers plays an important role in the initiation and maintenance of pruritus [ 43 , 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Pruritus Is Associated with an Increased Risk for the Diagnosis of Autoimmune Skin Blistering Diseases: A Propensity-Matched Global Study

et al. 2023

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Autoimmune bullous skin diseases (AIBDs), such as bullous pemphigoid (BP) and pemphigus, are characterized and caused by autoantibodies targeting structural proteins. In BP, clinical experience and recent systematic evaluation identified pruritus to be common and an important cause of impaired quality of life. Furthermore, chronic pruritus may be the sole clinical symptom of BP. In pemphigus, a retrospective study recently documented a high prevalence of pruritus. The temporal relation between pruritus and BP/pemphigus are, however, unknown. Likewise, the presence of pruritus in AIBDs other than BP and pemphigus is unknown. To address this, we performed propensity-matched retrospective cohort studies using TriNetX, providing real-world patient data to (i) assess the risk to develop AIBDs following the diagnosis of pruritus and (ii) vice versa. We assessed this in eight AIBDs: BP, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita, dermatitis herpetiformis, lichen planus pemphigoides (LPP), pemphigus vulgaris, pemphigus foliaceous, and paraneoplastic pemphigus (PNP). For all AIBDs, pruritus was associated with an increased risk for the subsequent diagnosis of each of the eight investigated AIBDs in 1,717,744 cases (pruritus) compared with 1,717,744 controls. The observed hazard ratios ranged from 4.2 (CI 3.2–5.5; p < 0.0001) in MMP to 28.7 (CI 3.9–211.3; p < 0.0001) in LPP. Results were confirmed in two subgroup analyses. When restricting the observation time to 6 months after pruritus onset, most HRs noticeably increased, e.g., from 6.9 (CI 6.2–7.9; p < 0.0001) to 23.3 (CI 17.0–31.8; p < 0.0001) in BP. Moreover, pruritus frequently developed following the diagnosis of any of the eight AIBDs, except for PNP. Thus, all AIBDs should be considered as differential diagnosis in patients with chronic pruritus.

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Section: Discussionmentioning

confidence: 99%

Pruritus Is Associated with an Increased Risk for the Diagnosis of Autoimmune Skin Blistering Diseases: A Propensity-Matched Global Study

et al. 2023

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“…68,69 Furthermore, patents for small molecule candidates targeting TRPA1 channels have been filed by several drug-developing pharma companies including Eli Lilly, Genentech/Roche, Algomedix Inc., Glenmark, Boehringer Ingelheim, Almirall S.A., Orion Corp., EA Pharm Co. and Mandom Corp. TRPA1 antagonists HC-030031 and GRC-17536 are effective anti-tussive mediators. 70,71 Recent findings have revealed GDC-0334, a TRPA1 antagonist to possess better target engagement in human subjects. In preclinical studies involving respiratory disease models, GDC-0334 exhibited inhibition toward edema formation, smooth muscle hyperreactivity, and cough response.…”

Section: Trpa1 As a Drug Targetmentioning

confidence: 99%

A Comprehensive Review on the Regulatory Action of TRP Channels: A Potential Therapeutic Target for Nociceptive Pain

Anand,

Rajagopal

2023

J Exp Neurosci

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The transient receptor potential (TRP) superfamily of ion channels in humans comprises voltage-gated, non-selective cation channels expressed both in excitable as well as non-excitable cells. Four TRP channel subunits associate to create functional homo- or heterotetramers that allow the influx of calcium, sodium, and/or potassium. These channels are highly abundant in the brain and kidney and are important mediators of diverse biological functions including thermosensation, vascular tone, flow sensing in the kidney and irritant stimuli sensing. Inherited or acquired dysfunction of TRP channels influences cellular functions and signaling pathways resulting in multifaceted disorders affecting skeletal, renal, cardiovascular, and nervous systems. Studies have demonstrated the involvement of these channels in the generation and transduction of pain. Based on the multifaceted role orchestrated by these TRP channels, modulation of the activity of these channels presents an important strategy to influence cellular function by regulating intracellular calcium levels as well as membrane excitability. Therefore, there has been a remarkable pharmaceutical inclination toward TRP channels as therapeutic interventions. Several candidate drugs influencing the activity of these channels are already in the clinical trials pipeline. The present review encompasses the current understanding of TRP channels and TRP modulators in pain and pain management.

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“…Several phase I and II clinical trials of TRPV1 antagonists have been conducted to examine their potential usefulness as analgesics. 21–23 David Julius has received the Nobel Prize in Physiology or Medicine in 2021 for the identification of transient receptor potential (TRP) and transient receptor-like protein functions. 24,25 The discovery of the molecular transducers underlying the senses of temperature and touch increased greatly our understanding of how the nervous system encodes sensory information.…”

Section: Introductionmentioning

confidence: 99%

Relation Between Reactive Oxygen Species Production and Transient Receptor Potential Vanilloid1 Expression in Human Skin During Aging

Favero,

Gianò,

Franco

et al. 2024

J Histochem Cytochem.

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Skin sensitivity and impaired epidermal barrier function are associated with aging and are at least partly due to increased production of reactive oxygen species (ROS). Transient receptor potential vanilloid1 (TRPV1) is expressed in keratinocytes, fibroblasts, mast cells, and endothelial cells in skin. We investigated in skin biopsies of adult and elderly donors whether TRPV1 expression is involved in the skin aging process. We found that aging skin showed a strongly reduced epidermal thickness, strongly increased oxidative stress, protease expression, and mast cell degranulation and strongly increased TRPV1 expression both in epidermis and dermis. Based on our findings, the aging-related changes observed in the epidermis of the skin level are associated with increased ROS production, and hypothesized alterations in TRPV1 expression are mechanistically linked to this process.

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Transient Receptor Potential Channels and Itch

Cited by 24 publications

References 63 publications

Pruritus Is Associated with an Increased Risk for the Diagnosis of Autoimmune Skin Blistering Diseases: A Propensity-Matched Global Study

Pruritus Is Associated with an Increased Risk for the Diagnosis of Autoimmune Skin Blistering Diseases: A Propensity-Matched Global Study

A Comprehensive Review on the Regulatory Action of TRP Channels: A Potential Therapeutic Target for Nociceptive Pain

Relation Between Reactive Oxygen Species Production and Transient Receptor Potential Vanilloid1 Expression in Human Skin During Aging

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