For more than 50 years we have known that glutamate is the main excitatory neurotransmitter in the brain but we have much more to learn about the function and regulation of glutamate. Our laboratory intends to elucidate the role of glutamate in sensory ganglia, which is the area of the nervous system where all primary sensory neurons are located. While the importance of the sensory ganglion in transmitting pain signals is undeniable, the function of glutamate in the ganglion has not been studied. Our recent experiments provide evidence that there is a significant release of glutamate in sensory ganglia, where it activates pain neurons. To firmly establish the role of glutamate in the ganglion, it is critical that we show its effects occur through receptors and that there are glutamate related changes in the ganglia following nerve injury. The experiments we propose involve pharmacologic modulation of glutamate receptors on sensory neurons to determine the behavioral effects. We will also use electrophysiological recording from whole, intact ganglia to determine the effects of glutamate on specific receptors in the ganglion. Using electron microscopy, we will also locate the cells in the sensory ganglion that have glutamate receptors on their surface that enables them "see" glutamate. From a scientific point of view these findings will provide a solid foundation for the notion that there is chemical communication (cross-excitation) between sensory neurons through non-synaptic (volume) transmission. This will lead to a comprehensive view of the neurochemical events occurring around sensory neurons. These findings will bring a fresh understanding of the sensory ganglion as a dynamic area where key chemical phenomena are involved in various forms of pain, from migraines, to intractable facial pain, from fibromyalgia to chronic low back pain. The sensory ganglion is an ideal area to study volume transmission, which is now being implicated in brain disorders such as epilepsy and schizophrenia.

Public Health Relevance

Chronic pain is a major social problem yet our treatments are not greatly improved in the past decades. By considering new mechanisms involving glutamate related actions we will open new avenues for our understanding of pain and the development of new pain reducing therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS079897-01A1
Application #
8510327
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Porter, Linda L
Project Start
2013-04-01
Project End
2015-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
1
Fiscal Year
2013
Total Cost
$235,313
Indirect Cost
$85,313
Name
University of California San Francisco
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Gong, Kerui; Kung, Ling-Hsuan; Magni, Giulia et al. (2014) Increased response to glutamate in small diameter dorsal root ganglion neurons after sciatic nerve injury. PLoS One 9:e95491