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Altered sensation along the distribution of the trigeminal nerve is a well-recognized complication of Multiple Sclerosis (MS). However, the mechanisms underlying trigeminal sensory disturbances in MS are poorly understood. This can be attributed, at least in part, to the lack of animal models that exhibit MS-like trigeminal dysfunction and pathology. The data presented in this thesis contributes to the literature by demonstrating that a particular animal model, experimental autoimmune encephalomyelitis (EAE), could be an invaluable tool for studying MS-related trigeminal sensory disturbances. The goal of Chapter 1 was to assess whether or not EAE could be used to study MS-related trigeminal dysfunction and pathology. I started by establishing a novel behavioral test in the lab which gave me the ability to assess facial sensitivity in freely moving mice. This test was based on a previously published protocol and involved applying puffs of air to the whisker pads of mice. Behaviors evoked by the air puffs were captured on a camera and graded according to a scoring system used in the aforementioned protocol. I found that prior to the induction of EAE, the puffs of air would typically evoke reflexive withdrawal behaviors. By contrast, following the induction of EAE the air puffs triggered pronounced nocifensive behaviors (e.g. facial swipes down the snout). Given the pronounced change in facial sensitivity, I next wanted to investigate trigeminal pathology that may be associated with this change in facial sensitivity. I used immunohistochemistry to assess inflammation and demyelination at several points along the trigeminal primary afferent pathway. I found that in tissue obtained from mice with EAE, inflammation and demyelination could be detected at the level of the trigeminal ganglion (TG), trigeminal nerve root, and trigeminal brainstem complex. Following up on the data obtained in Chapter 1, the goal for Chapters 2 and 3 was to further investigate mechanisms underlying the facial hypersensitivity observed in mice with EAE. In Chapter 2, I assessed the excitability of TG neurons in vitro using calcium imaging. I found that the sensitivity of TG neurons to pro-nociceptive agonists (e.g. capsaicin and adenosine triphosphate (ATP)) was unaltered by EAE. Additionally, the magnitude of the calcium responses evoked by these agonists was unaltered by EAE. By contrast, the magnitude of the calcium responses evoked by potassium chloride (KCl) was significantly greater in neurons obtained from animals with EAE relative to controls. Collectively, the data presented in Chapter 2 demonstrates that the excitability of trigeminal primary afferent neurons is increased in EAE. This change in excitability could be a major contributing factor to the altered facial sensitivity observed in mice with EAE. Finally, during my analysis of the trigeminal pathway in EAE, I noticed that expression of the astrocyte marker glial fibrillary acidic protein (GFAP) decreases at the trigeminal root entry zone. Given that astrocyte disruption is a rarely touched upon topic in neuroscience, I decided to follow-up on this finding and made it the focus of Chapter 3. There I demonstrate that in EAE, the loss of GFAP at the trigeminal root is highly heterogenous both within and between animals. I also show that the loss of GFAP is associated with an accumulation of amyloid precursor protein (APP), a marker of axonal injury. Upon further investigation, I found that tissue sections with GFAP loss had exacerbated inflammation and demyelination. Additionally, I provide evidence that astrocyte loss is not limited to the trigeminal root and can also be detected in the spinal cord. In order to identify a mechanism that may underlie trigeminal injury in EAE, I introduced a novel cell culture technique, immunopanning, to the lab. Using immunopan-purified astrocytes and cortical neurons, I demonstrate that injured astrocytes lose the capacity to support neurons in vitro. Collectively, the data presented in Chapter 3 suggests that EAE is associated with trigeminal nerve injury, which in turn may be mediated by a loss of astrocytes that protect the trigeminal nerve from inflammatory disease processes. In summary, the work presented in this thesis is the first to demonstrate that EAE is associated with trigeminal pathology and facial pain behaviors. In addition, this work reveals mechanisms that may contribute to trigeminal sensory disturbances in EAE and, potentially, MS.