Dr. Dong, trained in molecular neuroscience, has identified many genes specifically expressed in pain-sensing neurons in dorsal root ganglia. He is interested in studying the function of these genes in pain sensation by multiple approaches including molecular biology, mouse genetics, mouse behavior, and electrophysiology.
The laboratory will use these genes as molecular tools to understand the cellular properties of different subtypes of pain-sensing neurons with respect to neuronal circuitry in central projection and pain modalities. The laboratory also is investigating the molecular mechanism of how skin mast cells sensitize sensory nerves under inflammatory states.
Dr. Dong identified a nearly 50-member family of G protein-coupled receptor (GPCRs) called Mrgs.
Using mouse molecular and genetic techniques, Dr. Dong’s team found that the axons of Mrg-expressing nociceptors mainly innervate skin, but not visceral organs. This is thought to be the first known marker with such a specific innervation pattern.
His team also isolated several neuropeptides – including FMRFamide, NPFF, and g2-MSH – that function as ligands for Mrgs. Some Mrg ligands have been implicated in regulating pain sensitivity.
Dr. Dong also has isolated several novel nociceptor-specific molecules from the initial screen. Some encode ion channels and have very specific expression pattern similar to Mrgs.
Studies conducted in the Dong Lab have shown that nociceptors are highly diverse at molecular level, and the roles of these neurons in nociception are far from understood.
With nociceptor-specific genes in hand, Dr. Dong’s research team is in an advantageous position to combine molecular biology and genetics with animal behavior and electrophysiology to gain new insights into nociception.
Small-diameter nociceptive neurons whose cell bodies reside in dorsal root ganglia (DRG) and trigeminal ganglia (TG) play essential roles in pain signal detection, transmission, and modulation.
The peripheral axons of these pseudo-unipolar neurons innervate skin, muscle, and visceral organs to detect painful stimuli, while their central axons transmit these signals to the spinal cord dorsal horn.
One major contributor to hyperalgesia is augmented sensitivity of primary nociceptive neurons. Therefore, monitoring the activities of these neurons and axons is crucial to understand pain mechanisms.
In addition, by specifically expressing a genetically encoded Ca2+ sensitive indicator in almost all DRG and TG neurons in Pirt-GCaMP3 mice, Dong Lab researchers successfully detected activation of primary sensory neurons in the trigeminal system at peripheral and central terminals, as well as in their cell bodies, in tissue explant and slice preparation.
They were able to see peripheral neuronal hypersensitivity in both injured and uninjured nerves corresponding to chronic pain from skin territories innervated by these nerves.
Kim YS, Chu Y, Han L, Li M, Li Z, Lavinka PC, Sun S, Tang Z, Park C, Caterina MJ, Ren K, Dubner R, Wei F, Dong X. "Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain." Neuron. 2014 Feb 19;81(4):873-87. doi: 10.1016/j.neuron.2013.12.011. Epub 2014 Jan 23.
He SQ, Li Z, Chu YX, Han L, Xu Q, Li M, Yang F, Liu Q, Tang Z, Wang Y, Hin N, Tsukamoto T, Slusher B, Tiwari V, Shechter R, Wei F, Raja SN, Dong X, Guan Y. "MrgC agonism at central terminals of primary sensory neurons inhibits neuropathic pain." Pain. 2014 Mar;155(3):534-44. doi: 10.1016/j.pain.2013.12.008. Epub 2013 Dec 11.
Tang Z, Kim A, Masuch T, Park K, Weng H, Wetzel C, and Dong X. " Pirt functions as an endogenous regulator of TRPM8." Nature Communications July 2013.
Zhao X, Tang Z, Zhang H, Atianjoh FE, Zhao JY, Liang L, Wang W, Guan X, Kao SC, Tiwari V, Gao YJ, HOffman PN, Cui H, Li M, Dong X, TAo YX. " A long noncoding RNA contributes to neuropathic pain by silencing Kv1.2 in primary afferent neurons." Nature Neuroscience. July 2013.
Han L, Ma C, Liu Q, Weng H, Cui Y, Tang Z, Kim Y, Nie H, Qu L, Patel K, Li Z, McNeil B, He S, Guan Y, Xiao B, LaMotte R, Dong X. "A subpopulation of nociceptors specifically linked to itch." Nature Neuroscience 16:174-182.