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.
Hachisuka, J., H. R. Koerber* and S. E. Ross* (2019). "Selective-cold output through a distinct subset of lamina I spinoparabrachial neurons." Pain.
Gatto, G., K. M. Smith, S. E. Ross and M. Goulding (2019). "Neuronal diversity in the somatosensory system: bridging the gap between cell type and function." Curr Opin Neurobiol 56: 167-174.
Snyder, L. M., M. C. Chiang, E. Loeza-Alcocer, Y. Omori, J. Hachisuka, T. D. Sheahan, J. R. Gale, P. C. Adelman, E. I. Sypek, S. A. Fulton, R. L. Friedman, M. C. Wright, M. G. Duque, Y. S. Lee, Z. Hu, H. Huang, X. Cai, K. A. Meerschaert, V. Nagarajan, T. Hirai, G. Scherrer, D. H. Kaplan, F. Porreca, B. M. Davis, M. S. Gold*, H. R. Koerber* and S. E. Ross*(2018). "Kappa Opioid Receptor Distribution and Function in Primary Afferents." Neuron 99(6): 1274-1288 e1276.
Hachisuka, J., Y. Omori, M. C. Chiang, M. S. Gold, H. R. Koerber* and S. E. Ross* (2018). "Wind-up in lamina I spinoparabrachial neurons: a role for reverberatory circuits." Pain 159(8): 1484-1493.
Hachisuka, J, Baumbauer, KM, Omori, Y, Snyder, LM, Koerber, HR*, and S. E. Ross* (2016). Semi-intact ex vivo approach to investigate spinal somatosensory circuits. Elife5.
Kardon AP, Polgar E, Hachisuka J, Snyder LM, Cameron D, Savage S, Cai X, Karnup S, Fan CR, Hemenway GM, Bernard CS, Schwartz ES, Nagase H, Schwarzer C, Watanabe M, Furuta T, Kaneko T, Koerber HR, Todd AJ*, Ross SE* (2014) Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord. Neuron 2014;82(3):573-86.
Duan B, Cheng L, Bourane S, Britz O, Padilla C, Garcia-Campmany L, Krashes M, Knowlton W, Velasquez T, Ren X, Ross SE, Lowell BB, Wang Y, Goulding M, Ma Q. (2014) Identification of spinal circuits transmitting and gating mechanical pain. Cell 159(6):1417-32.
Braz JM, Juarez-Salinas D, Ross SE, Basbaum AI. (2014) Transplant restoration of spinal cord inhibitory controls ameliorates neuropathic itch.J Clin Invest. 124(8):3612-6.