Background and aims: Cinnamaldehyde (CA) elicits itch sensation in humans. Histamine and other itch mediators require expression of TRPV1, TRPA1, and/or TRPV4 in pruriceptor transduction.  We presently investigated if CA-evoked scratching behavior requires TRPV1, TRPA1 and/or TRPV4 using knockout (KO) mice lacking these channels.  We also used calcium imaging to investigate if CA activates sensory dorsal root ganglion (DRG) neurons in wildtype (WT) and KO mice. 
Methods:  We scored hindlimb scratch bouts and forelimb wipes directed to the site of cheek injection of CA in wildtype (WT) and TRPV1, TRPA1 and TRPV4 KO mice.   DRG neurons from each genotype were acutely dissociated, cultured and loaded with FURA-2 for ratiometric calcium imaging of their responses to bath application of CA. 
Results: In WT mice, CA elicited significant, dose-related bouts of hindlimb scratching but not forelimb wiping.   CA-evoked scratching was significantly reduced (~50%)  in TRPV1 and TRPV4KOs but not in TRPA1KOs.  As expected, DRG cells from TRPA1KOs were unresponsive to CA.  Significantly fewer DRG cells from TRPV4KOs were activated by CA, consistent with the behavioral data.  Curiously, significantly more DRG cells from TRPV1KOs vs. WTs were activated by CA.   
Conclusions: TRPA1 is not required for CA-evoked itch behavior.  TRPV4 in sensory neurons is important for CA-evoked itch, since scratching and DRG neuronal responses were both reduced in TRPV4KOs.  TRPV1 is also important for CA-evoked itch; however, since CA activated DRG cells from TRPV1KOs, TRPV1 may have a role in itch independent of sensory neurons.  
Acknowledgment: supported by NIH ARO57194

CINNAMALDEHYDE-EVOKED SCRATCHING IN MICE REQUIRES DIRECT OR INDIRECT ACTIVATION OF TRPV4- AND TRPV1- BUT NOT TRPA1-EXPRESSING SENSORY NEURONS