• Zhong-Qiu Zhao, Xian-Yu Liu, Joseph Jeffry, W K Ajith Karunarathne, Jin-Lian Li, Admire Munanairi, Xuan-Yi Zhou, Hui Li, Yan-Gang Sun, Li Wan, Zhen-Yu Wu, Seungil Kim, Fu-Quan Huo, Ping Mo, Devin M Barry, Chun-Kui Zhang, Ji-Young Kim, N Gautam, Kenneth J Renner, Yun-Qing Li, and Zhou-Feng Chen.
• Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
• Neuron. 2014 Nov 19;84(4):821-34.

UnlabelledCentral serotonin (5-hydroxytryptophan, 5-HT) modulates somatosensory transduction, but how it achieves sensory modality-specific modulation remains unclear. Here we report that enhancing serotonergic tone via administration of 5-HT potentiates itch sensation, whereas mice lacking 5-HT or serotonergic neurons in the brainstem exhibit markedly reduced scratching behavior. Through pharmacological and behavioral screening, we identified 5-HT1A as a key receptor in facilitating gastrin-releasing peptide (GRP)-dependent scratching behavior. Coactivation of 5-HT1A and GRP receptors (GRPR) greatly potentiates subthreshold, GRP-induced Ca(2+) transients, and action potential firing of GRPR(+) neurons. Immunostaining, biochemical, and biophysical studies suggest that 5-HT1A and GRPR may function as receptor heteromeric complexes. Furthermore, 5-HT1A blockade significantly attenuates, whereas its activation contributes to, long-lasting itch transmission. Thus, our studies demonstrate that the descending 5-HT system facilitates GRP-GRPR signaling via 5-HT1A to augment itch-specific outputs, and a disruption of crosstalk between 5-HT1A and GRPR may be a useful antipruritic strategy.Video AbstractCopyright © 2014 Elsevier Inc. All rights reserved.

26 keywords...

hide…