Involvement of TRPV4 in Serotonin-Evoked Scratching

J Invest Dermatol. 2016 Jan;136(1):154-160. doi: 10.1038/JID.2015.388.


Several thermosensitive transient receptor potential channels (transient receptor potential vanilloid type-1, -3; transient receptor potential cation channel, subfamily A, member 1) have been implicated in itch. In contrast, the role of transient receptor potential vanilloid type-4 (TRPV4) in itch is unknown. Therefore, we investigated if TRPV4, a temperature-sensitive cation channel, plays an important role in acute itch in mice. Four different pruritogens, including serotonin (5-hydroxytryptamine [5-HT]), histamine, SLIGRL (protease-activated receptors 2/mas-related G-protein-coupled receptor C11 agonist), and chloroquine (mas-related G-protein-coupled receptor A3 agonist), were intradermally injected into mice and itch-related scratching behavior was assessed. TRPV4 knockout mice exhibited significantly fewer 5-HT-evoked scratching bouts compared with wild-type mice. Notably, no differences between TRPV4 knockout and wild-type mice were observed in the number of scratch bouts elicited by SLIGRL and histamine. Pretreatment with a TRPV4 antagonist significantly attenuated 5-HT-evoked scratching in vivo. Using calcium imaging in cultured primary murine dorsal root ganglion neurons, the response of neurons after 5-HT application, but not other pruritogens, was significantly lower in TRPV4 knockout compared with wild-type mice. A TRPV4 antagonist significantly suppressed 5-HT-evoked responses in dorsal root ganglion cells from wild-type mice. Approximately 90% of 5-HT-sensitive dorsal root ganglion neurons were immunoreactive for an antibody to TRPV4, as assessed by calcium imaging. These results indicate that 5-HT-induced itch is linked to TRPV4.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Disease Models, Animal
  • Histamine / adverse effects
  • Histamine / pharmacology
  • Immunohistochemistry
  • Injections, Intradermal
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Pruritus / chemically induced
  • Pruritus / metabolism*
  • Pruritus / pathology
  • Random Allocation
  • Receptor, PAR-2 / drug effects
  • Receptor, PAR-2 / metabolism
  • Reference Values
  • Sensory Receptor Cells / drug effects
  • Serotonin / adverse effects
  • Serotonin / pharmacology
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*


  • Receptor, PAR-2
  • TRPV Cation Channels
  • Trpv4 protein, mouse
  • Serotonin
  • Histamine