Our recent studies of the communication between neuronal soma and satellite glial cells (SGCs) in dorsal root ganglia (DRGs) suggest that somatic release of ATP in response to afferent nerve stimulation activates purinergic P2X7 receptors (P2X7Rs) in SGCs. Under normal conditions, tonic activation of P2X7Rs in SGCs reduces P2X3R expression in neuronal somata, thus exerting inhibitory control of neuronal activity. Following high frequency nerve stimulation, activation of P2X7Rs evokes cytokine release causing an enhancement of P2X3R activity in somata and an increase in the excitability of neurons. The P2X7R-mediated SGC-neuronal soma feedback controls under inflammation and nerve injury conditions have not been well established. This knowledge is essential for understanding the generation and maintenance of abnormal chronic pain. The goal of this application is to understand changes in neuronal soma-SGC communication during different phases of chronic pain development. We hypothesize that following injury, an increase in cytokine release switches P2Rmediated SGC-soma communication from inhibitory to excitatory feedback control, thus initiating the development of abnormal pain states. A subsequent large increase in ATP release, which activates P2X7Rs and pannexin-1, produces a large enhancement of SGC-soma communication and thus leads to the transition from the development to the maintenance phase of chronic pain. We will (1) determine if P2R-mediated SGC-soma communication changes during the development and maintenance phase of chronic pain, (2) determine the mechanisms underlying the change in SGC-soma communication and (3) determine if modulation of SGC-soma communication is a valid strategy for the management of chronic pain.
This project is designed to understand the mechanism underlying the over-excitation of sensory neurons after injury, a phenomenon contributing to chronic pain conditions. The study will determine injury-induced changes in neuron-glial cell communication and suggest better therapeutic targets for chronic pain control.
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