The goal of our research is to functionally dissect the neural circuits that underlie pain and itch.
• Why does scratching cause relief from itch?
• Are itch and pain encoded by distinct labeled-lines?
• Why is injured tissue tender to the touch?
• How can pain persist after an injury heals?
We are investigating these questions and more at the circuit level--trying to understand the role of individual neurons within the neural circuits that mediate pain and itch. To do this, we use genetic approaches to label and regulate the activity of small subsets of neurons. This involves generating and analyzing genetically modified mice, live cell imaging, circuit tracing, optogenetics and behavioral studies.
For instance, our work has identified a subset of inhibitory neurons (which we term B5-I neurons) that are required for normal itch sensation; mice lacking these neurons suffer from persistent pathological itch. This work provides the first evidence implicating a loss of inhibitory neurons within the dorsal horn in pathological itch. Furthermore, B5-I neurons are the first component of an itch circuit to be labeled genetically, and so studying these neurons provides us with a unique opportunity to unravel itch circuits. We are now using this molecular handle to define the molecular, electrophysiological and morphological characteristics of these neurons and characterize exactly, how, where and when they regulate itch.
Significance: Improved understanding of the neural basis of pain and itch is of clinical relevance to millions of people worldwide that suffer from clinical conditions, particularly chronic pain, that result from of maladaptive changes in neural circuitry.
Ross, S. E, McCord, A.E., Jung, C., Atan, D., Mok, S.I., Hemberg, M., Kim, Tae-Kyung, Salogiannis, J., Hu, L., Cohen, S., Lin, Y., Harrar, D., McInnes, R. R. and Greenberg, M. E. Bhlhb5 and Prdm8 form a repressor complex involved in neuronal circuit assembly. Neuron 73(2): 292-303, 2011.
Ross, S. E. Pain and itch: insights into the neural circuits of aversive somatosensation in health and disease. Current Opinion in Neurobiology 21: 1–8, 2012
Ross, S.E., Mardinly, A., McCord, A.E., Zurawski, J., Cohen, S., Jung, C., Hu, L., Mok, S.I., Shah, A., Savner, E., Tolias, C., Corfas, R., Chen, S., Inquimbert, P., Xu, Y., McInnes, R.R., Rice, F.L., Ma, Q., Corfas, G., Woolf, C. and Greenberg, M.E. Loss of inhibitory interneurons in the dorsal horn of the spinal cord gives rise to abnormal itch in Bhlhb5 mutant mice. Neuron 2010 25;65(6): 886-98, 2010.
Ross S. E., Greenberg, M.E. and Stiles, C.D. Basic Helix-Loop-Helix Factors in Cortical Development. Neuron 39: 13-25, 2003.
Ross, S.E., Hemati, N., Longo, K.A., Bennett, C.N., Lucas, P.C., Erickson, R.L. and MacDougald, O.A. Inhibition of adipogenesis by Wnt signaling. Science 289: 950-3, 2000.