Pain is a public health issue affecting the lives of nearly 116 million adults in the US, annually. Understanding the physiological and phenotypic changes that occur in response to painful stimuli is of tremendous clinical interest, but, the complexity of pain and the lack of a representative in vitro model hinders the development of new therapeutics. Pain stimuli are first perceived and transmitted by the neurons within the dorsal root ganglia (DRG) which become hyperexcitable under these conditions. It has now been established that satellite glial cells (SGCs) that ensheathe the DRG cell body actively contribute to this neuronal dysregulation. To understand the role of SGCs in this pain circuit, first, we looked at the development of SGCs within the DRG of rats, and we showed that SGCs developed postnatally, and appeared morphologically, transcriptionally and functionally similar to Schwann cells precursors (SCs), supporting the idea that these cells may exhibit multipotent behavior. Secondly, we describe here, a three-dimensional in vitro model of the DRG which is functionally characterized on a microelectrode array (MEA). This model can be used to assess the long-term recording of spontaneous activity from bundles of axons while preserving the neuronal-SGC interactions similar to those observed in vivo. Furthermore, using capsaicin, an agonist of the TRPV1 nociceptive receptor, we show that this model can be used as an in vitro assay to acquire evoked responses from nociceptive neurons. Overall, this study advances our knowledge on the development and differentiation of SGCs and establishes a novel functional three-dimensional model for the study of SGCs. This model can now be used as a tool to study the underlying basis of neuronal dysregulation in pain.
Doctor of Philosophy (Ph.D.)
College of Medicine
Burnett School of Biomedical Sciences
Length of Campus-only Access
Doctoral Dissertation (Open Access)
George, Dale, "Dissecting the Components of Neuropathic Pain" (2018). Electronic Theses and Dissertations. 5765.