Fluorescence immunolocalization of the receptor for the class of migraine drugs known as the "triptans," serotonin 5HT1D receptor (red) and the inflammatory neurotransmitter substance P (green) in the rat dorsal root ganglia.  Their co-localization (in yellow) has implications for the peripheral mechanism of action of the triptan drugs, not only in migraine but possibly also in other forms of pain. A nuclear counterstain (DAPI) is shown in blue and also labels nuclei in glia and connective tissue. 

Research Summary

Our laboratory is interested in the mechanisms through which tissue or nerve injury result in persistent/chronic pain. A major question is the extent to which different features of the pain experience are evoked by the activity of selected subsets of "pain fibers" (i.e. nociceptors) vs. by differential patterns of activity generated across multiple populations of afferents. To understand the functional significance of the molecular complexity of the nociceptor, we study pain behavior in mice with deletions of different genes that code for transducers of injury stimuli or that code for different neurotransmitter receptors and second messenger molecules. Among the many molecules that we have studied are the TRP channels (including TRPVI and TRPM8) as well as major second messenger molecules, notably the gamma isoform of protein kinase C, which we have implicated in the development of nerve injury-induced neuropathic pain. More recently, we have initiated a parallel series of studies that is examining the circuits that underlie the production of itch. Our focus is on the differential contribution of subsets of nociceptors to scratching behavior evoked by distinct pruritogens, including histamine, endothelin-1 and serotonin.