Messengers of sensations – non-neuronal contributions to mechanosensitivity.

Touch and pain systems have evolved sophisticated ways to perceive various external stimuli like temperature or mechanical force.

In 2010, Coste et al. identified the ion channel Piezo2 as a sensor for mechanical stimulation in primary sensory neurons.

I showed that loss of Piezo2 induces profound loss of mechanically evoked responses in mice and humans, and it is indispensable for mechanical allodynia – in which gentle touch is perceived as painful.

It is now clear that Piezo2 is a major detector of mechanical stimulation in multiple classes of mechanoreceptors.In many sensory systems, excitation of sensory neuron is modulated or evoked by a peripheral cell (e.g. hair cell for the sense of hearing).

I hypothesize that, also in somatosensory system, transmitters released by the skin play an important role in tuning Piezo2-dependent and -independent mechanotransduction. Based on my experience I propose an approach focusing on in vivo assays and genetic strategies. I will address this problem at multiple levels of biological organization.

First, I will investigate cellular mechanisms of skin mechanosensitivity. Next, I will test the role of keratinocyte-nerve crosstalk. Last, I will investigate modulation of axon terminal excitability in the skin.

The proposed research is curiosity driven, but it examines basic processes that have direct implication for understanding and solving clinical problems such as the search for improved local anesthesia, chronic pain or fibromyalgia.