Gina Story, Ph.D.

    storyg@morpheus.wustl.edu

Assistant Professor of Anesthesiology
Washington University Pain Center
Basic Research Section

B.S. in Biology (1995)
Allegheny College

Ph.D. in Biomedical Sciences, Cellular and Molecular Biology
Kent State University
The Northeastern Ohio Universities College of Medicine

Posdoctoral training (2001-2005)
The Scripps Research Institute

Story Lab Web Site

Thermosensation represents a significant component of pain sensation. For example, cold sensation is altered in some chronic pain states: patients with neuropathic pain (an ongoing pain state caused by nervous system injury) often suffer from cold allodynia (a painful response to an otherwise non-painful cooling stimulus). Although successful treatments of pain do exist, many are inadequate for some conditions or cause unacceptable side effects suggesting a search for new therapeutic targets is warranted.

Research in my lab is focused on the molecular basis of detection of both painful and pleasant touch stimuli in healthy and diseased states. We start with the basic physiological and anatomical framework of the peripheral sensory neuron. These neurons originate within the dorsal root ganglia (DRG), innervate targets such as the skin and joints and represent a "first response system" for relaying information regarding our environment. Until rather recently, how the DRG neurons sense cold, heat or mechanical stimuli at the molecular level and then relay that information to the spinal cord and brain has remained particularly elusive.

It is now known that members of a specialized group of T ransient R eceptor P otential (TRP) ion channel proteins directly detect thermal and chemical stimuli corresponding to sensations of heat, cold and pain. Some of these proteins (dubbed thermoTRPs) are found specifically in specialized skin cells, while others are expressed in specialized subsets of DRG neurons. We utilize thermoTRP channels as molecular markers of temperature- and pain-sensing neurons. By examining these neurons further at the molecular and functional level, our aim is to uncover additional mechanisms involved in acute, inflammatory and chronic pain states. To this end, we employ techniques such as molecular biology, gene expression profiling (microarrays), electrophysiology, live-cell imaging, mouse genetics and behavior.

In situ hybridization study of thermoTRP channel expression in DRG neurons
reveals populations of cold-, heat- and pain-sensing neurons. The left panel
shows individual neurons expressing mRNA transcripts of two cold-activated
thermoTRPs, the cool- and menthol-sensing channel TRPM8 (red) and TRPA1
(green), a channel activated by painfully cold temperatures and by burning
compounds such as cinnamon oil and mustard oil (wasabi). The fact that red and
green cells do not overlap, suggests two functionally distinct populations of
neurons that sense cooling temperatures in addition to compounds that are
cooling (TRPM8) or burning (TRPA1). Do TRPA1-expressing neurons transmit a
cold or a burning signal to the brain?

The right panel shows expression of TRPV1 (red cells), a thermoTRP channel
activated by painfully hot temperatures and capsaicin (the burning component
of hot chili peppers). We also used a green probe against TRPA1 in this panel,
but in this case no green cells appear; TRPA1 cells overlap with a subset of
TRPV1 cells and therefore appear yellow. What signal do these neurons
transmit—hot or cold? To tackle this question, we propose a basic
model of sensory coding by the thermoTRPs. Neurons that transmit a pleasantly
cool signal (like the sensations of menthol) express TRPM8, TRPV1-expressing
neurons transmit a hot signal (like hot chili) and neurons expressing both
TRPA1 and TRPV1 send a generic pain signal to the brain (like burning,
pricking or aching).

Story, G.M. (2006) The emerging role of TRP channels in mechanisms of temperature and pain sensation. Current Neuropharmacology 4: 183-196.

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Macpherson, L.J., Hwang, S.W., Miyamoto, T., Dubin, A.E., Patapoutian, A., and Story, G.M. (2006) More than cool: promiscuous relationships of menthol and other sensory compounds.  Molecular and Cellular Neuroscience 32: 335-343.

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Story, GM, and Gereau, RW. (2006) Numbing the senses: Role of TRPA1 in mechanical and cold sensation. Neuron 50(2): 277-89.

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Moqrich, A., Hwang, S.W., Earley, T.J., Petrus, M.J., Murray , A.N., Spencer, K.S.R., Andahazy, M., Story, G.M. , Patapoutian, A. (2005) Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin. Science, 307(5714):1468-72.

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Bandell, M.*, Story, G.M. *, Hwang, S.W., Viswanath, V., Eid, S.R., Petrus, M.J., Earley, T.J., Patapoutian, A. (2004). Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41: 1-20.

*These authors contributed equally to this work.

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Viswanath, V., Story, G.M., Peier, A.M., Petrus, M.J., Lee, V.M., Hwang, S.W., Patapoutian, A., Jegla, T. (2003) Opposite thermosensor in fruitfly and mouse. Nature 423 (6942): 822-3.

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Patapoutian, A., Peier, A.M., Story, G.M. , Viswanath, V. (2003)     ThermoTRP channels and beyond: mechanisms of temperature sensation. Nat. Rev. Neurosci. 4(7): 529-39.

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Story, G.M. , Peier, A.M., Reeve, A.J., Eid, S.R., Mosbacher, J., Hricik, T.R., Earley, T.J., Hergarden, A.C., Andersson, D.A., Hwang, S.W., McIntyre, P., Jegla, T., Bevan, S. Patapoutian, A. (2003). ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112(6): 819-829.

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Peier, A.M., Reeve, A.J., Andersson, D.A., Moqrich, A., Earley, T.J., Hergarden, A.C., Story, G.M. , Colley, S., Hogenesch, J.B., McIntyre, P., Bevan, S., Patapoutian, A. A heat-sensitive TRP channel expressed in keratinocytes. (2002). Science 296(5575): 2046-2049.

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Peier, A.M., Moqrich, A., Hergarden, A.C., Reeve, A.J., Andersson, D.A., Story, G.M. , Earley, T.J., Dragoni, I. , McIntyre, P., Bevan, S., Patapoutian, A. (2002). A TRP channel that senses cold stimuli and menthol. Cell 108(5): 705-715.

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