Dissertation
Neuroimmune contributions to pain development after spinal cord injury: exploring macrophage-mediated dysfunction in the dorsal root ganglia
Doctor of Philosophy (Ph.D.), Drexel University
Sep 2019
DOI:
https://doi.org/10.17918/y508-jp08
Abstract
Spinal cord injury (SCI) damages sensory systems and causes chronic, intractable neuropathic pain. Inflammation in the dorsal root ganglia (DRG) in response to SCI may contribute to nociceptor dysfunction and pain development. Little is known of the immune signaling events that transpire in the DRG after SCI that could induce pathological changes in the nociceptor and drive pain. This body of work examined the role of macrophages in the DRG in the development of neuropathic pain after SCI. Macrophages were found to infiltrate the DRG early after SCI, in response to the rapid but transient elevation of a chemokine and macrophage chemoattractant, CCL2. The magnitude of increase in CCL2 differed in rats with similar injuries, and affected the inflammatory nature of the macrophage response. After pain establishment, macrophage presence was exacerbated in rats with SCI that develop pain, and DRG immune environment was found to be pro-inflammatory. Inhibiting the CCL2-mediated macrophage response prior to pain development induced pain rather than preventing it, and this was found to be due to a decrease in pro- as well as anti-inflammatory cytokines and macrophages. These studies serve as a basis for ongoing work exploring the effect of macrophage phenotype and secretome on pathological nociceptor dysfunction. Understanding the neuroimmune interactions between macrophages and nociceptors in the DRG may lead to the development of pain preventative and pain modulatory therapies.
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Details
- Title
- Neuroimmune contributions to pain development after spinal cord injury
- Creators
- Soha J. Chhaya - DU
- Contributors
- Megan R. Detloff (Advisor) - Drexel University (1970-)John D. Houle (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiii, 205 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Neurology; Drexel University
- Other Identifier
- 11370; 991014632836004721