The sense of touch consists of the perception of discrete types of thermal, mechanical, and chemical stimuli. Electrophysiologists have long realized that recognition of touch is executed by neurons of restricted specificity, such that warm stimuli can activate a different class of neurons than cold stimuli, for instance. However, little is known about the molecular basis of touch perception. We are characterizing the genes involved in the first step of touch sensation: those that encode the molecular sensors of touch stimuli.

Our lab has identified the first gene involved in our ability to sense cold temperatures. This gene, trpm8, encodes for a protein present at the plasma membrane of cold-sensing neurons that belongs to the Transient Receptor Potential (TRP) channel family. Interestingly, TRPM8 is also activated by menthol, a commonly-used cooling compound.

We have also identified another TRP family member, TRPA1, as a noxious cold receptor. We have since discovered that TRPA1 is also activated by a variety of pungent compounds (including the active ingredients in garlic, cinnamon, and horseradish) through their ability to irreversibly covalently modify cysteines. Therefore, TRPA1 can act as a sensor of chemical damage to trigger pathways leading to pain sensation.

TRPV3, another sensory channel we have identified, responds to warm and hot temperatures. Unlike other thermoTRPs, TRPV3 is mainly expressed in keratinocytes rather than in DRG neurons, suggesting that a novel mechanism of cell-cell communication is involved in this sensory modality.

We are continuing to identify additional sensory receptors while working towards a more complete understanding of the mechanism of activation of these channels and their in vivo roles in the sense of touch. We are using transgenic and genomic technologies to address these questions. These approaches will yield insights into the basic biology of the peripheral nervous system and may also have an impact on novel treatments for pain.