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      TRPV1: Role in Skin and Skin Diseases and Potential Target for Improving Wound Healing

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          Abstract

          Skin is innervated by a multitude of sensory nerves that are important to the function of this barrier tissue in homeostasis and injury. The role of innervation and neuromediators has been previously reviewed so here we focus on the role of the transient receptor potential cation channel, subfamily V member 1 (TRPV1) in wound healing, with the intent of targeting it in treatment of non-healing wounds. TRPV1 structure and function as well as the outcomes of TRPV1-targeted therapies utilized in several diseases and tissues are summarized. In skin, keratinocytes, sebocytes, nociceptors, and several immune cells express TRPV1, making it an attractive focus area for treating wounds. Many intrinsic and extrinsic factors confound the function and targeting of TRPV1 and may lead to adverse or off-target effects. Therefore, a better understanding of what is known about the role of TRPV1 in skin and wound healing will inform future therapies to treat impaired and chronic wounds to improve healing.

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          The capsaicin receptor: a heat-activated ion channel in the pain pathway.

          Michael Caterina, Mark Schumacher, Makoto Tominaga … (1997)
          Capsaicin, the main pungent ingredient in 'hot' chilli peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system. We have used an expression cloning strategy based on calcium influx to isolate a functional cDNA encoding a capsaicin receptor from sensory neurons. This receptor is a non-selective cation channel that is structurally related to members of the TRP family of ion channels. The cloned capsaicin receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo.
          Article 0 comments Cited 667 times – based on 0 reviews     Review now
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            Wound Healing: A Cellular Perspective

            Melanie Rodrigues, Nina Kosaric, Clark Bonham … (2019)
            Wound healing is one of the most complex processes in the human body. It involves the spatial and temporal synchronization of a variety of cell types with distinct roles in the phases of hemostasis, inflammation, growth, re-epithelialization, and remodeling. With the evolution of single cell technologies, it has been possible to uncover phenotypic and functional heterogeneity within several of these cell types. There have also been discoveries of rare, stem cell subsets within the skin, which are unipotent in the uninjured state, but become multipotent following skin injury. Unraveling the roles of each of these cell types and their interactions with each other is important in understanding the mechanisms of normal wound closure. Changes in the microenvironment including alterations in mechanical forces, oxygen levels, chemokines, extracellular matrix and growth factor synthesis directly impact cellular recruitment and activation, leading to impaired states of wound healing. Single cell technologies can be used to decipher these cellular alterations in diseased states such as in chronic wounds and hypertrophic scarring so that effective therapeutic solutions for healing wounds can be developed.
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              Impaired nociception and pain sensation in mice lacking the capsaicin receptor.

              M. J. Caterina, A. Leffler, A. Malmberg … (2000)
              The capsaicin (vanilloid) receptor VR1 is a cation channel expressed by primary sensory neurons of the "pain" pathway. Heterologously expressed VR1 can be activated by vanilloid compounds, protons, or heat (>43 degrees C), but whether this channel contributes to chemical or thermal sensitivity in vivo is not known. Here, we demonstrate that sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli. VR1-/- mice showed normal responses to noxious mechanical stimuli but exhibited no vanilloid-evoked pain behavior, were impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation. Thus, VR1 is essential for selective modalities of pain sensation and for tissue injury-induced thermal hyperalgesia.
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                Author and article information

                Contributors
                David A. Hart: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 07 June 2021
                Publication date Collection: June 2021
                Volume: 22
                Issue: 11
                Electronic Location Identifier: 6135
                Affiliations
                [1 ]Department of Dermatology, School of Medicine, UC Davis, Sacramento, CA 95816, USA; mdbagood@ 123456ucdavis.edu
                [2 ]Dermatology Section, VA Northern California Health Care System, Mather, CA 95655, USA
                Author notes
                [* ]Correspondence: rrisseroff@ 123456ucdavis.edu ; Tel.: +1-(916)-551-2606
                Author information
                https://orcid.org/0000-0002-9639-5654
                https://orcid.org/0000-0001-7813-0858
                Article
                Publisher ID: ijms-22-06135
                DOI: 10.3390/ijms22116135
                PMC ID: 8201146
                PubMed ID: 34200205
                SO-VID: bedff31f-0f86-4f53-bc0b-09b8802099f3
                Copyright © © 2021 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 20 April 2021
                Date accepted : 01 June 2021
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: trpv1,wound healing,skin,keratinocytes,pilosebaceous unit,nociceptors
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: trpv1, wound healing, skin, keratinocytes, pilosebaceous unit, nociceptors

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