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Overexpressed transient receptor potential vanilloid 3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2.
J Neurosci. 2008 Dec 17; 28(51):13727-37.JN

Abstract

The ability to sense changes in the environment is essential for survival because it permits responses such as withdrawal from noxious stimuli and regulation of body temperature. Keratinocytes, which occupy much of the skin epidermis, are situated at the interface between the external environment and the body's internal milieu, and have long been appreciated for their barrier function against external insults. The recent discovery of temperature-sensitive transient receptor potential vanilloid (TRPV) ion channels in keratinocytes has raised the possibility that these cells also actively participate in acute temperature and pain sensation. To address this notion, we generated and characterized transgenic mice that overexpress TRPV3 in epidermal keratinocytes under the control of the keratin 14 promoter. Compared with wild-type controls, keratinocytes overexpressing TRPV3 exhibited larger currents as well as augmented prostaglandin E(2) (PGE(2)) release in response to two TRPV3 agonists, 2-aminoethoxydiphenyl borate (2APB) and heat. Thermal selection behavior and heat-evoked withdrawal behavior of naive mice overexpressing TRPV3 were not consistently altered. Upon selective pharmacological inhibition of TRPV1 with JNJ-17203212 [corrected], however, the keratinocyte-specific TRPV3 transgenic mice showed increased escape responses to noxious heat relative to their wild-type littermates. Coadministration of the cyclooxygenase inhibitor, ibuprofen, with the TRPV1 antagonist decreased inflammatory thermal hyperalgesia in transgenic but not wild-type animals. Our results reveal a previously undescribed mechanism for keratinocyte participation in thermal pain transduction through keratinocyte TRPV3 ion channels and the intercellular messenger PGE(2).

Authors+Show Affiliations

Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21025, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19091963

Citation

Huang, Susan M., et al. "Overexpressed Transient Receptor Potential Vanilloid 3 Ion Channels in Skin Keratinocytes Modulate Pain Sensitivity Via Prostaglandin E2." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 28, no. 51, 2008, pp. 13727-37.
Huang SM, Lee H, Chung MK, et al. Overexpressed transient receptor potential vanilloid 3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2. J Neurosci. 2008;28(51):13727-37.
Huang, S. M., Lee, H., Chung, M. K., Park, U., Yu, Y. Y., Bradshaw, H. B., Coulombe, P. A., Walker, J. M., & Caterina, M. J. (2008). Overexpressed transient receptor potential vanilloid 3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 28(51), 13727-37. https://doi.org/10.1523/JNEUROSCI.5741-07.2008
Huang SM, et al. Overexpressed Transient Receptor Potential Vanilloid 3 Ion Channels in Skin Keratinocytes Modulate Pain Sensitivity Via Prostaglandin E2. J Neurosci. 2008 Dec 17;28(51):13727-37. PubMed PMID: 19091963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpressed transient receptor potential vanilloid 3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2. AU - Huang,Susan M, AU - Lee,Hyosang, AU - Chung,Man-Kyo, AU - Park,Una, AU - Yu,Yin Yin, AU - Bradshaw,Heather B, AU - Coulombe,Pierre A, AU - Walker,J Michael, AU - Caterina,Michael J, PY - 2008/12/19/entrez PY - 2008/12/19/pubmed PY - 2009/1/13/medline SP - 13727 EP - 37 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 28 IS - 51 N2 - The ability to sense changes in the environment is essential for survival because it permits responses such as withdrawal from noxious stimuli and regulation of body temperature. Keratinocytes, which occupy much of the skin epidermis, are situated at the interface between the external environment and the body's internal milieu, and have long been appreciated for their barrier function against external insults. The recent discovery of temperature-sensitive transient receptor potential vanilloid (TRPV) ion channels in keratinocytes has raised the possibility that these cells also actively participate in acute temperature and pain sensation. To address this notion, we generated and characterized transgenic mice that overexpress TRPV3 in epidermal keratinocytes under the control of the keratin 14 promoter. Compared with wild-type controls, keratinocytes overexpressing TRPV3 exhibited larger currents as well as augmented prostaglandin E(2) (PGE(2)) release in response to two TRPV3 agonists, 2-aminoethoxydiphenyl borate (2APB) and heat. Thermal selection behavior and heat-evoked withdrawal behavior of naive mice overexpressing TRPV3 were not consistently altered. Upon selective pharmacological inhibition of TRPV1 with JNJ-17203212 [corrected], however, the keratinocyte-specific TRPV3 transgenic mice showed increased escape responses to noxious heat relative to their wild-type littermates. Coadministration of the cyclooxygenase inhibitor, ibuprofen, with the TRPV1 antagonist decreased inflammatory thermal hyperalgesia in transgenic but not wild-type animals. Our results reveal a previously undescribed mechanism for keratinocyte participation in thermal pain transduction through keratinocyte TRPV3 ion channels and the intercellular messenger PGE(2). SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/19091963/Overexpressed_transient_receptor_potential_vanilloid_3_ion_channels_in_skin_keratinocytes_modulate_pain_sensitivity_via_prostaglandin_E2_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=19091963 DB - PRIME DP - Unbound Medicine ER -