Pruritus is one of the most widespread symptom in dermatology. Typically, during the
molecular transduction of itch, the activation of metabotropic receptors on the pruriceptive nerve endings
stimulated either by exogenous pruritogenic molecules or endogenous signals, leads to the activation or
sensitization of an ion channel crucial in the consequent depolarization of the neuronal membrane. Recent
research indicated that these ion channels mostly belong to the transient receptor potential (TRP) family of ion
channels and show significant overlap with those involved in nociception (TRPV1, TRPA1). TRPM3 was
recently identified as a novel thermosensitive channel contributing to nociception. However the role of TRPM3
in the development of pruritus has not been studied yet. Therefore, in the current project we aim at
investigating the potential role of TRPM3 in the transduction of pruritus.
We investigated the itch inducing effect of various pruritogenic substances on wild type and TRPM3 C57/Bl6
mice, in the “cheek model” paradigm, which allows to differentiate the nociceptive and pruriceptive behavioural
responses. During this paradigm, pruritogenic substances diluted into 10μl vehicle (PBS+7%TWEEN-80) were
injected subcutaneously into the cheek of mouse and reactive behaviour were recorded and analysed
quantitatively
To investigate the role of TRPM3 in the development of pruritus, we treated n=8-13 wt and TRPM3 mice with
the pruritogen histamine, the non-histaminergic serotonin,endothelin-1, chloroquine, the algogen capsaicin and
the TRPM3 specific pregnenolone sulphate (PS), compared with vehicle treatment. Our findings argue for the
involvement of TRPM3 only in certain pain, but not itch responses: histamine and serotonin evoked similar
scratching behaviour on both KO and wt animals; whereas TRPM3 activator PS evoked only pain related
responses which were abolished in TRPM3-/- animals.

Pruriceptive role of TRPM3