ATP is one of the substances released from damaged tissues. It activates P2X receptors in primary sensory neurons and contributes to pain and discomfort. The long-term goal of this research is to understand the role of P2X receptors in nociception. In this grant our focus will be to understand the plasticity in P2X receptors following inflammation and nerve injury. We hypothesize that activation of P2X receptors is greatly enhanced under injurious conditions as results of an increase in the activity of protein kinases, interactions with other receptors and changes in expression of P2X receptors. In vivo and in vitro approaches will be used to test this hypothesis. We will (1) determine the effects of ATP on nociceptive behaviors, (2) identify the functional properties of sensory afferents responsive to ATP and quantify the responses of these afferents to ATP, (3) determine the properties of ATP-induced currents and intracellullar Ca 2+ mobiliTation and (4) determine the mechanisms underlying the potentiation of ATP responses by examining the effects of protein kinases and nociceptive mediators, i.e., bradykinin and prostaglandin E2, on ATP-evoked current and Ca 2+ responses and by determining the expression of P2X receptors. Behavioral experiments will be performed on normal, inflamed and nerve injured rats in vivo. Electrophysiological experiments will be performed on skin and DRG-nerve preparations and single DRG neurons isolated from these rats. Membrane currents will be measured with patch electrodes. Single-unit activity will be monitored with extracellular electrodes, intracellular Ca2+ concentrations will be studied using Ca2+ dyes and P2X receptor expression will be examined with Western analyses. These studies should provide a better understanding of the mechanisms underlying the plasticity of P2X receptors under injurious conditions. The information will be essential for developing new strategies for the treatment of chronic pain.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Porter, Linda L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Medical Br Galveston
Schools of Medicine
United States
Zip Code
Wilkes, Denise M; Orillosa, Susan J; Hustak, Erik C et al. (2018) Efficacy, Safety, and Feasibility of the Morphine Microdose Method in Community-Based Clinics. Pain Med 19:1782-1789
Huang, Li-Yen; Gu, Yanping (2017) Epac and Nociceptor Sensitization. Mol Pain 13:1744806917716234
Lin, You-Min; Fu, Yu; Winston, John et al. (2017) Pathogenesis of abdominal pain in bowel obstruction: role of mechanical stress-induced upregulation of nerve growth factor in gut smooth muscle cells. Pain 158:583-592
Gu, Yanping; Li, Guangwen; Chen, Yong et al. (2016) Epac-protein kinase C alpha signaling in purinergic P2X3R-mediated hyperalgesia after inflammation. Pain 157:1541-50
Gu, Yanping; Wang, Congying; Li, Guangwen et al. (2016) EXPRESS: F-actin links Epac-PKC signaling to purinergic P2X3 receptors sensitization in dorsal root ganglia following inflammation. Mol Pain 12:
Chen, Yong; Li, Guangwen; Huang, Li-Yen Mae (2015) p38 MAPK mediates glial P2X7R-neuronal P2Y1R inhibitory control of P2X3R expression in dorsal root ganglion neurons. Mol Pain 11:68
Lin, You-Min; Fu, Yu; Wu, Chester C et al. (2015) Colon distention induces persistent visceral hypersensitivity by mechanotranscription of pain mediators in colonic smooth muscle cells. Am J Physiol Gastrointest Liver Physiol 308:G434-41
Huang, Li-Yen M; Gu, Yanping; Chen, Yong (2013) Communication between neuronal somata and satellite glial cells in sensory ganglia. Glia 61:1571-81
Li, Guangwen; Ma, Fei; Gu, Yanping et al. (2013) Analgesic tolerance of opioid agonists in mutant mu-opioid receptors expressed in sensory neurons following intrathecal plasmid gene delivery. Mol Pain 9:63
Zhang, Hong-Hong; Hu, Ji; Zhou, You-Lang et al. (2013) Promoted interaction of nuclear factor-?B with demethylated cystathionine-?-synthetase gene contributes to gastric hypersensitivity in diabetic rats. J Neurosci 33:9028-38

Showing the most recent 10 out of 35 publications