Date of Award
Summer 8-8-2025
Level of Access Assigned by Author
Open-Access Thesis
Degree Name
Doctor of Philosophy (Biomedical Science)
Department
Biomedical Sciences
First Committee Advisor
Robert Burgess
Second Committee Member
Mike Burman
Third Committee Member
Ling Cao
Additional Committee Members
Geoff Ganter
Ian Meng
Abstract
Neonatal intensive care units (NICUs) provide life-saving care for preterm and sick neonates, but many medical procedures are painful and stress-inducing. Even a routine NICU procedure, such as the “heel lancing” blood-draw procedure, is an acutely painful, repetitive manipulation that has lasting negative impacts on pain perception and anxiety responses. The intersection of nociception and negative affect occurs in a brain region called the central nucleus of the amygdala (CeA), and neurons expressing corticotropin-releasing factor (CRF) have been implicated in studies of both anxiety and pain. Using a two-hit model of trauma-induced pain vulnerability—where repetitive needle prickings occur during the first week of life, followed by a second stressor (e.g., fear conditioning) during adolescence—our lab has observed a mechanical hypersensitivity in rats that endured early life pain that manifests only after fear conditioning. We have also observed changes to expression and activation of CeA-CRF neurons after early life pain with an acute increase followed by a lasting reduction in the number of CRF cells in the right CeA of adolescent male rats. However, the relationship between these changes and the observed behavioral outcomes remains unclear, as does the function of the remaining CRF cell population. We hypothesize that the remaining population of CRF-expressing CeA neurons are functionally altered by early life pain and primed to respond more readily, such that vulnerability to stress-induced hypersensitivity is increased. Through chemogenetic inhibition of the amygdala, or specifically CeA-CRF neurons, we demonstrate that development of stress-induced mechanical hypersensitivity after early life pain is completely reversed through silencing the amygdala. Inhibiting only CeA-CRF neurons during fear conditioning led to a partial reversal of the hypersensitivity, suggesting that other populations of cells also play critical roles. CeA-CRF neurons are indeed affected by early life manipulations, as early life pain results in a lasting hyperexcitability of CeA-CRF neurons during adolescence; however, it appears this was not exclusive to CRF-expressing cells, as increased excitability was also observed in non-CRF CeA cells. Despite not being necessary for the development of trauma-induced hypersensitivity, activation of CRF-expressing neurons is sufficient to induce hypersensitivity after early life pain. In all, this dissertation provides evidence that suggests that CeA-CRF neurons may have pro-nociceptive properties that are exacerbated by early life pain and result in maladaptive responding to subsequent traumatic events.
Recommended Citation
Tomasch, Megan, "The Role of Corticotropin-Releasing Factor-Expressing Neurons in the Central Nucleus of the Amygdala on Neonatal Trauma-Induced Vulnerability to Tactile Hypersensitivity" (2025). Electronic Theses and Dissertations. 4253.
https://digitalcommons.library.umaine.edu/etd/4253