Siemens Lab
Temperature Detection and Thermoregulation

Sensory TRP Ion Channels

 

Plant products mimic physical stimuli. Capsaicin, present in hot chili peppers, menthol,produced by mint plants, and mustard oil act as agonists for TRPV1, TRPM8 and TRPA1, respectively.

Harmful signals are detected by peripheral somatosensory nerve endings and relayed along the spinal cord to higher brain centers where a pain percept is generated. Normally nociception –and the ensuing perception of pain– serves an important protective function geared to prevent tissue damage and to foster healing. However, under certain pathological conditions pain can become chronic and outlast its physiological role. While the etiology of pathological and persistent forms of pain is diverse, one driving force is the sensitization of nociceptive neurons that promotes pain hypersensitivity. Members of the extended TRP ion channel family not only participate in the detection of noxious stimuli but also in the sensitization of peripheral sensory neurons. In particular, the capsaicin receptor TRPV1 has been identified as downstream integrator of many inflammatory pathways to facilitate pain hypersensitivity. A large body of literature attests to a crucial pathological role for TRPV1 and numerous inflammatory signaling cascades have been found to sensitize the receptor. However, endogenous signaling cascades that counteract TRPV1 sensitization and that keep the receptor in check have remained elusive. We have identified such an inhibitory pathway and found that the GABAB receptor has the capacity to revert TRPV1 sensitization. We are interested in uncovering the GABAB-TRPV1 crosstalk mechanistically and characterize how it modulates pain sensitivity.

More generally –and beyond a modulatory role of TRPV1– we are also interested in the cognate agonist of the GABAB receptor, the neurotransmitter GABA, and its function in the peripheral nervous system. We speculate that it may also counteract the activity of other nociceptive pathways via unrecognized signaling cascades.