Mechanisms of Satellite Glial Cells in Chronic Pain Genesis and Maintenance: A Novel Method for Analgesic Research by Charles Jiang (VI) Abstract
Chronic pain is a common condition that involves hypersensitivity of neurons. Many treatments currently target the neurons of the nervous system but often result in adequate responses. Located in the peripheral nervous system, satellite glial cells (SGCs) are a type of glial cell that closely envelope the cell bodies of neurons in the sensory ganglia. SGCs have been recently proven to play a direct role in the pathogenesis of pain. Because of their location early in the pain sensation pathway and their close relationship with neurons, they are a possible therapeutic target for chronic pain. The activation cascade of SGCs includes ATP, hypersensitivity of purinergic receptors, release of substance P and cytokine, changes in expression of ion channels, increased gap junction coupling, and a sustained calcium wave. There is evidence that these changes caused by SGCs contribute to chronic pain by altering neuronal activity. In particular, purinergic receptor P2X7R plays a major role in this cascade, promoting further ATP release, increasing ATP sensitivity, and contributing to a pro-inflammatory feedback loop. In this paper, we propose an experiment to block P2X7R with A-740003 as a treatment for chronic pain. Two tests would be conducted on rats. The first test would confirm P2X7R activation, A-740003 blockage, and downstream effects in vitro. The second test would determine the effect of blockage of P2X7R with A-740003 in animals exhibiting hyperalgesia in vivo. Hypothetical results suggest confirmation of the significant role of P2X7R in SGC activation, that A-740003 inhibits this role, and that A-740003 successfully returned animals with hyperalgesia to normal levels of nociception.
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