Recent studies of cytokine actions in the spinal cord and dorsal root ganglia suggest that neuron-glia interactions are important in initiating and maintaining chronic pain states. How this is accomplished remains unclear. Disorders of the orofacial complex often produce intense chronic pain in patients and results in devastating consequences in their well being. The long-term goal of this research is to understand neuron-glia interactions in the trigeminal ganglion (TG), the primary afferent structure for the orofacial region. Our focus will be to understand the critical role that transmitters released from neuronal somata (cell bodies) of TGs play in neuron- satellite glial cell communication. We hypothesize that excessive firing in TG neurons elicits somatic release of ATP from neuronal somata. ATP activates satellite cells and evokes cytokine release from these cells. Cytokines in turn sensitize the neuronal somata and further increase their activity. In vitro and in vivo approaches will be used to test this hypothesis of positive feedback loop. We will (1) identify the transmitters released from neuronal somata of TGs (2) examine the communication between neuron and satellite cells (3) determine the effects of cytokines on P2X and TRPV receptor-mediated responses, (4) examine the action of cytokines on nociceptive responses in rats and determine the possibility of using siRNA to down-regulate receptors involved in neuron-glia communication and thus to relieve orofacial nociception. Normal, inflamed and nerve-ligated rats will be used. Transmitter release and membrane currents will be measured with patch pipettes;intracellular Ca2+ concentrations will be monitored with Ca2+ dyes;expression of P2X and TRPV receptors will be examined with immunocytochemistry and Western analyses. These studies should provide a better understanding of the mechanisms underlying neuron-glia interactions in TGs. The knowledge will be critical for designing better therapies for the treatment of orofacial pain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE017813-05
Application #
7858029
Study Section
Special Emphasis Panel (ZDE1-GH (50))
Program Officer
Kusiak, John W
Project Start
2006-07-15
Project End
2012-01-31
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
5
Fiscal Year
2010
Total Cost
$346,198
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Neurosciences
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
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
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:
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
Chen, Yong; Li, Guangwen; Huang, Li-Yen Mae (2012) P2X7 receptors in satellite glial cells mediate high functional expression of P2X3 receptors in immature dorsal root ganglion neurons. Mol Pain 8:9
Wilkes, Denise; Li, Guangwen; Angeles, Carmina F et al. (2012) A large animal neuropathic pain model in sheep: a strategy for improving the predictability of preclinical models for therapeutic development. J Pain Res 5:415-24
Gu, Yanping; Chen, Yong; Zhang, Xiaofei et al. (2010) Neuronal soma-satellite glial cell interactions in sensory ganglia and the participation of purinergic receptors. Neuron Glia Biol 6:53-62
Wang, Congying; Li, Guang-Wen; Huang, Li-Yen Mae (2007) Prostaglandin E2 potentiation of P2X3 receptor mediated currents in dorsal root ganglion neurons. Mol Pain 3:22

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