Mason Guest Distinguished Professor, Department of Neuroscience and Cell Biology
Sabbatical with Professor Erwin Neher, Max-Planck-Institut Fur Biophsikalische Chemie, Germany
Staff Fellow, National Institutes of Health
Postdoctoral Fellow, Physiology, Mayo Clinic
Ph.D. in Biophysics, The State University of New York at Buffalo
Molecular and Cellular Mechanisms of Chronic Pain
The research focus of this laboratory is to understand the mechanism underlying chronic pain and nociception. We have concentrated our studies on plastic changes in cell signaling following nerve or inflammatory lesions. Dorsal root ganglion (DRG) neurons and dorsal horn neurons in the spinal cord and in the caudal medulla play a central role in the transmission and integration of nociceptive information. Understanding the membrane properties of these neurons, their responses to ATP, glutamate and opioids and the involvement of G-proteins and second messenger signaling under normal and injurious conditions have led to insights into the basis of abnormal sensory information processing in injurious states.
Another research focus is to understand the mechanism of ATP release between the cell body of a DRG neuron and its surrounding satellite glial cells and to determine the significance of this release and the involvement of purinergic receptors in neuron-satellite glial cell communication.
The third research interest is to design an effective genetic approach for the treatment of chronic pain. Increasing mu-opioid receptor expression in DRGs using adeno-associated viral vectors has proven to be a promising strategy for improving opioid potency in relieving neuropathic pain. This strategy should be useful for patients with spinal cord or nerve injury, back pain and limb loss, who are unresponsive to conventional opioid therapy.
Patch recordings, calcium and dye imaging, receptor gene modification, western analyses and behavioral testing are the techniques used in these studies.
Huang L.-Y. M., Gu, Y, Chen, Y. Communication Between Neuronal Somata and Satellite Glial Cells in Sensory Ganglia. Glia 61:1571-1581, 2013.
Wilkes, D., Li, G., Angeles, C. F., Patterson, J. T., Huang, L.-Y. M. A large animal neuropathic pain model in sheep: a strategy for improving the predictability of preclinical models for therapeutic development. Journal of Pain Research 5:415-424, 2012.
Chen, Y., Zhang, X., Wang, C. Li, G.W., Gu. Y. and Huang, L.-Y. M. Activation of P2X7 receptors in glial satellite cells reduces pain through downregulation of P2X3 receptors in nociceptive neurons, Proc. Natl. Acad. Sci. 105:16773-16778, 2008.
Zhang, X., Chen, Y, Wang, C. and Huang, L.-Y. M. Neuronal somatic ATP release triggers neuron-satellite glial cell communication in dorsal root ganglia, PNAS 104:9864-9869, 2007
Wang, C., Gu, Y. Li, G.W., and Huang, L.-Y. M., A critical role of cAMP sensor Epac in switching protein kinase signaling in prostaglandin E2-induced potentiation of P2X3 receptor currents in inflamed rats J. Physiol (London) 584.1:191-203, 2007
Gu, Y., Xu, Y., Li, G.W., and Huang, L.-Y.M. Remote nerve injection of mu-opioid receptor adeno-associated viral vector increases antinociception of intrathecal morphine, J. Pain, 6:447-54, 2005
Chen, Y., Gu, Y., Wang, C., Li, G.W., Huang, L.-Y. M. Sensitization and enhanced trafficking of P2X3 receptors in the neuropathic pain state. Pain 119 38-48, 2005
Xu, G.-Y. and Huang, L.-Y.M. Ca2+/calmodulin-dependent protein kinase II potentiates ATP responses by promoting trafficking of P2X receptors. PNAS. 101:11868-11873, 2004.
Xu, Y., Gu, Y., Wu, P., Li, G.-W. and Huang, L.-Y.M. Efficiencies of transgene expression in nociceptive neurons through different routes of delivery of adeno-associated viral vectors. Human Gene Therapy 14:897-906, 2003.
Xu, Y., Gu, Y., Xu, G.Y., Wu, P., Li, G.W., and Huang L.-Y.M. Adeno-associated viral transfer of opioid receptor gene to primary sensory neurons: A strategy to increase opioid antinociception. PNAS 100:6204-6209, 2003.
Wu, P., Tarasenko, Y.I., Gu, Y., Huang, L.-Y.M., Coggeshall, R.E. and Yu, Y. Region-specific generation of cholinergic neurons from fetal human neural stem cells grafted in adult rat. Nature Neurosci. 5:1271-1278, 2002.
Xu G.-Y. and Huang L.-Y. M. Peripheral inflammation sensitizes P2X receptor mediated responses in rat dorsal root ganglion neurons. J. Neurosci. 22:93-102, 2002