Zhou-Feng Chen, Ph.D.
Developmental, Regenerative and Stem Cell Biology Program
Molecular Genetics and Genomics Program
6640 Clinical Sciences Research Building
behavior, itch, pain, sensory systems, skin, spinal cord
Molecular and cellular mechanisms of itch sensation
All animals must have somatic sensations which permit them to sense external environmental stimuli, including chemical, mechanical and electrical inputs so that they would adapt and respond accordingly. Sensation of itch is the least understood among all somatic sensations (pain, touch, temperature, itch, body posture etc).
Scratch is an innate reflex (genetically programmed), and may occur in the absence of the brain. In contrast, itch is a perception originated in the brain. Itch is an unpleasant sensation that evokes the desire to scratch. Scratching response of animals provides a relatively simple behavioral output enabling us to study underlying neural circuits and accompanying signaling mechanisms.
A fundamental question we are interested is how our brain perceives itch as itch, pain as pain. Is the itch signal transmitted through an itch-specific neuronal pathway? What is the molecular basis of itch sensation?
We use the mouse as the model system to address these important questions. Mouse serves the best animal model for elucidating molecular and neuronal mechanisms of itch circuit because this simple reflex can be easily observed, quantified and manipulated by pharmacological, molecular and genetic approaches.
We are using multi-disciplinary approaches including molecular, cellular, biochemical, genetic and electrophysiological approaches to understand neural circuits and signaling mechanisms of itch sensation, as well as their interactions with the skin and immune systems.
Zhao ZQ, Liu XY, Jeffry J, Karunarathne WK, Li JL, Munanairi A, Zhou XY, Li H, Sun YG, Wan L, Wu ZY, Kim S, Huo FQ, MO P, Barry DM, Zhang CK, Kim JY, Gautam N, Renner KJ, Li YQ, Chen ZF. (2014). Descending Control of Itch Transmission by the Serotonergic System via 5-HT1A-Facilitated GRP-GRPR Signaling. Neuron (In press)
Zhao ZQ, Wan L, Liu XY, Huo FQ, Li H, Barry DM, Krieger S, Kim S, Liu ZC, Xu J, Rogers BE, Li YQ, Chen ZF. (2014). Cross-Inhibition of NMBR and GRPR Signaling Maintains Normal Histaminergic Itch Transmission. J Neurosci, 34(37):12402-14. PMCID: PMC4160775
Zhao ZQ, Huo FQ, Jeffry J, Hapmton L, Demehri S, Kim S, Liu XY, Barry DM, Wan L, Liu ZC, Li H, Turkoz A, Ma K, Cornelius LA, Kopan R, Battey JF, Zhong J and Chen ZF. (2013). Chronic itch development in sensory neurons requires BRAF signaling pathways. J. Clin Invest. 123 (11), 4769-4780. PMCID: PMC3809799
Liu XY, Liu ZC, Sun YG, Ross M, Kim SI, Tsai FF, Li QF, Jeffry J, Kim JY, Loh HH and Chen ZF. (2011). Unidirectional cross activation of GRPR by MOR1D uncouples itch and analgesia-induced by opioids. Cell 147(2): 447-458. PMCID: PMC3197217
Sun YG, Zhao ZQ, Meng XL, Yin J and Chen ZF. (2009). Cellular basis of itch sensation. Science 325: 1531-1534. PMCID: PMC2786498
Zhao ZQ, Gao YJ, Sun YG, Zhao CS, Gereau RW. and Chen ZF. (2007). Central serotonergic neurons are differentially required for opioid analgesia but not for morphine tolerance or morphine reward. Proc. Natl. Acad. Sci. USA. 104(36): 14519-24. PMCID: PMC1964813
Sun YG, and Chen ZF. (2007) Gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord. Nature, 448: 700-703.
Zhao ZQ, Chiechio S, Sun YG, Zhang KH, Zhao CS, Scott M, Johnson R., Deneris E., Renner K., Gereau RW. and Chen ZF. (2007) Mice lacking central serotonergic neurons show enhanced inflammatory pain and an impaired analgesic response to antidepressant drugs.J. Neurosci. 27: 6045-6053.
Zhao ZQ, Scott M., Chiechio S, Wang JS, Renner K, Gereau R., Johnson R., Deneris E., and Chen ZF. (2006). Lmx1b is required for maintenance of central serotonergic neurons and mice lacking central serotonergic system exhibit normal locomotor activity. J. Neurosci. 26: 12781-88.
Ding YQ, Marklund U, Yuan W, Wegman L, Ericson J, Deneris E, Johnson RL, and Chen ZF. (2003). Lmx1b is essential for the development of serotonergic neurons. Nat. Neurosci, 6:933-938.
Last Updated: 11/17/2014 11:41:50 AM