Dissertation
Neuroimmune contributions to mouse chronic neuropathic pain: macrophages play a dual role in sensory discriminative and affective components of pain
Doctor of Philosophy (Ph.D.), Drexel University
Dec 2023
DOI:
https://doi.org/10.17918/00001960
Abstract
Spinal cord injury (SCI) directly damages ascending pain pathways producing concurrent immune cell activation/recruitment and behavioral alterations including chronic neuropathic pain and comorbid depression. Over half of individuals with SCI experience chronic pain, and recent emphasis has been placed on the biopsychosocial consequences in addition to deficits in pain localization that encompass the "pain experience." Importantly, a robust immune response within pain-related neural circuits is associated with alterations in pain and anxiodepressive behaviors. First, we determined that the mouse unilateral C5 SCI model had high face validity with human SCI pain, mimicking both the sensory discriminative and mood-related deficits as well as the macrophage response along the sensory neuroaxis. Then, we tested the hypothesis that augmenting the peripheral macrophage response in forepaw innervating dorsal root ganglia (DRGs) prevents nociceptor-mediated sensory discriminative and supraspinally-mediated pain-related anxiodepressive-like behaviors after SCI by administering known macrophage chemoattractant, CCL2 intraganglionically at the time of SCI. An eGFP reporter on the LysM gene in these mice revealed that monocyte-derived macrophages infiltrate the DRG early after SCI and are maintained chronically. Driving anti-inflammatory macrophages into the DRG ameliorated pain-related behaviors while exacerbating depressive-like behaviors in some SCI mice. Interestingly, increased macrophage infiltration into the C7-8 spinal cord correlated with increased pain identifying another target for immunomodulation. This research highlights a mechanistic approach to inversely alter nociceptive and cortically-mediated behaviors emphasizing the importance of basic scientific discovery for understanding the pathophysiology of chronic neuropathic pain and comorbid depression in affected individuals.
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Details
- Title
- Neuroimmune contributions to mouse chronic neuropathic pain
- Creators
- Jonathan Houston Richards
- Contributors
- Megan R. Detloff (Advisor)Veronica J. Tom (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiv, 218 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Neurology; Drexel University
- Other Identifier
- 991021819013904721