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The plasticity of intercellular communication and the polarization of glial cells in pain centers following spinal cord injury
Thesis   Open access

The plasticity of intercellular communication and the polarization of glial cells in pain centers following spinal cord injury

Daniel D. Freeman
Master of Science (M.S.), Drexel University
Jun 2023
DOI:
https://doi.org/10.17918/00001673
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Abstract

Biology Spinal ganglia Polarization Sonic hedgehog signaling Spinal cord--Wounds and injuries
Spinal cord injury (SCI) is a neurological condition which often results in the development of chronic pain. In addition to neuropathic pain brought about by the injury itself, inflammation can drive pain signal transmission by contributing to the hyperexcitability of nociceptors and second order neurons in the dorsal root ganglia (DRG) and dorsal horn of the spinal cord, respectively. One of the key mediators of inflammation in pain centers is Sonic hedgehog (Shh) signaling in glial and immune cells. This signaling pathway has been shown to have neuroprotective effects including the resolution of inflammation. In addition to Shh signaling, glial and immune cell polarization to neurotoxic and neuroprotective phenotypes can contribute to the inflammatory nature of pain centers. This body of work examines the roles of Shh signaling and glial and immune cell polarization in contributing to inflammation and the development of chronic pain following SCI. A conditional knockdown of Shh signaling did not further increase pain following SCI compared to wildtype mice with SCI. However, when looking at the relative expression of markers pertaining to neurotoxic and neuroprotective populations of glial and immune cells, as well as the secretory factors that comprise the microenvironments of the dorsal horn and DRG, we find that certain analytes contribute to the development of pain following SCI moreso than others. These studies serve as a basis for ongoing work pertaining to the identification of targets and the development of therapeutics aimed at reducing pain in individuals who have sustained a SCI.

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