Functional magnetic resonance imaging (fMRI) studies performed to date have focused on brain structures rostral to the thalamus, although the first level of sensory information and pain transmission occurs at the spinal cord (SC). The primary goal of this project is to map activity using fMRI, from the entire cervical SC and brainstem following innocuous and noxious stimuli before and after peripheral sensitization in normal human volunteers. This study is unique in that it determines functional activity throughout the lower neural axis in response to mechanical stimuli that are perceived as painful only after sensitization. Functional MRI studies of the SC were carried out in 18 healthy individuals in a 3T Siemens Magnetom Trio. Innocuous touch and brush (n=8), and noxious touch (n=10) stimuli were applied before and after peripheral sensitization. Peripheral sensitization was induced by topical application of capsaicin. Functional image data spanned from the C7/T1 disc to the superior edge of the thalamus and analyzed using a general linear model to discriminate signal intensity changes from physiological motion. Normalized results were combined to demonstrate the number of volunteers showing activity at each location on a voxel-by-voxel basis. Areas of activity were superimposed onto anatomical transverse drawings and identified visually with comparison to several stereotaxic atlases. The results from this study confirm previous reports that a non-noxious stimulus translates into a pain response after peripheral sensitization. The brush stimulus, before sensitization activated areas in the ipsilateral dorsal horn (DH), gracile and cuneate nuclei in the medulla and areas surrounding the dorsal column medial lemniscal pathway. Peripheral sensitization produced activity in the contralateral ventral horn (VH), typical of a pain response. The innocuous von Frey stimulus produced activity in typical sensory centres in the DH and brainstem before sensitization, and areas more consistent with a noxious response after sensitization. When examining equi-nociceptive stimuli in a control versus sensitized state, the noxious touch stimuli showed similar activation patterns even though the force of the filaments were different. In all experiments there was indication of descending modulation as activity was observed in the periaqueductal gray, midbrain red nuclei and pontine reticular formation. This study demonstrates how non-painful and pain information is transmitted from the dorsal spinal horn to the brain in healthy individuals and how peripheral sensitization induces changes in non-noxious stimuli that correlate with pain sensory transmission. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2008-09-24 20:13:08.655

To date, most studies investigating the neural signature of pain in humans have focused on the brain, and those studies concerned with more caudal areas (such as the spinal cord (SC) or brainstem) have used only experimental models of pain. The objectives of this study were 1) to determine the neural activity in the human brainstem and SC that is caused by a noxious mechanical stimulus and 2) to compare the neural response to noxious stimuli in healthy controls and a patient population diagnosed with peripheral neuropathic pain. The SC and brainstem contain important synaptic points in several major pain pathways, and comparing the neural response between a control and patient population in these areas provides a more complete picture of healthy and pathological pain processing. Functional MRI studies of the SC and brainstem were carried out in healthy control subjects and patients diagnosed with carpal tunnel syndrome (CTS) in a 3T Siemens Magnetom Trio. Subjects reported the point at which the pressure (in mmHg, applied to the wrist at the location of the median nerve) corresponded to a pain level of 2, 4, and 6 on a numerical 11 point pain scale. Spatially normalized group results superimposed on anatomical templates in the axial orientation were visually identified using several stereotaxic atlases. We observed consistent signal intensity change in areas implicated in the transmission and modulation of pain in both control and CTS groups. Both groups showed a similar decrease in signal change with increasing pain, as results at pain level 2 are predominantly positive signal change and at pain level 6 are typically negative. This may indicate a reduction in the tonic inhibition of painful sensations. Differences between groups were readily visible in regions anatomically consistent with the dorsal horn (DH) of the cervical SC, rostral ventromedial medulla (RVM), dorsolateral pontine tegmentum (DLPT), and midbrain periaqudectal gray (PAG). The anatomical variation in signal change between groups may represent, for the first time, a visualization of the functional difference between healthy and pathological pain processing in the SC and brainstem using spinal fMRI. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2010-08-03 14:46:01.7

Olfactory ensheathing cells (OECs) are the chief glial population of the mammalian olfactory nervous system and are thought to be responsible for the successful directional growth of new olfactory axons throughout the life of adult mammals. Due to this unique property, OECs have been targeted as a potential cellular transplantation therapy for spinal cord injury. In order to effectively isolate OECs for intraspinal transplantation, more knowledge must be gained on their phenotypic properties. We investigated the neurochemical features of OECs in a variety of mammalian species (including hamsters, rabbits, monkeys, mice, and pigs) using three biomarkers: glial fibrillary acidic protein (GFAP), S100β, and α-smooth muscle actin (αSMA). In addition, we tested the ability of a few biomatrices to sustain and promote OEC growth and survival in vitro. The rationale for using biomatrices is to provide a supportive environment for glial and axonal growth in the spinal lesion. Here, we found that mucosal and bulbar OECs from all five of the aforementioned mammalian species express S100β. Expression of GFAP, however, was not consistent across the five species. Both mucosal and bulbar OECs of monkeys express αSMA; only bulbar OECs of hamsters and only mucosal OECs of rabbits express αSMA as well. Though αSMA immunostaining was not detected in the OECs of adult mice, in adult mutant mice lacking αSMA expression, OECs displayed perturbed ultrastructural morphology. None of the biomatrices used (methacrylated glycol chitosan, arginine-glycine-aspartic acid – grafted methacrylated glycol chitosan, and agarose) were able to promote OEC proliferation. Isolated strips of rodent olfactory lamina propria (the deep connective tissue layer in the olfactory mucosa containing primary sensory axons and OECs) showed sustained growth when cultured for 10 days. In sum, these findings highlight the following points: the efficacy of S100β and αSMA as biomarkers for mammalian OECs in vivo; the potential for isolated strips of lamina propria to provide a natural, supportive environment for OECs during intraspinal transplantation; the failure of methacrylated glycol chitosan and its derivatives, as well as agarose, to promote OEC proliferation. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2012-07-27 15:29:47.642

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Wheelchair propulsion is an important part of daily living for many people with spinal cord injuries (SCI's). The aim of this project was to establish the validity of using a new approach for measuring wheelchair propulsion ability. The variation in methods observed by subject's hands in contacting and propelling their wheelchair, namely, using the push rims only; wedging the hands between push rims and tyre and grasping both push rims and tyres, highlighted that earlier studies using instrumented push rims (including the SMART ) for people with tetraplegia would not provide a true indication of propulsion ability for the participants in this study. As a result, a new inertia dynamometer was built and calibrated for measuring wheelchair propulsion ability. Kinetic and kinematic models were developed to calculate wheelchair propulsion parameters such as power output, wheelchair velocity and arm motion patterns. After testing 22 subjects with different SCI levels, the results indicated that arm function was a more important factor in wheelchair propulsion, in terms of power output, than trunk stability and strength. More importantly, people with C5/C6 tetraplegia had a significantly reduced capability in terms of wheelchair propulsion compared with other subjects with a lower lesion (T1-T8, T9-T12 and L1-S5). A further study for quantifying the contribution of triceps function on improving wheelchair propulsion for people with tetraplegia was performed by comparing kinetic and kinematics parameters in C5/C6 tetraplegia subjects. Depending on the control of elbow extension, the subjects were divided into groups with: no active elbow extension, deltoid to triceps transfer surgery (TROIDS) to provide elbow extension, and incomplete C5/C6 tetraplegia with retained active triceps function providing elbow extension. The results demonstrated that the restoration of triceps following TROIDS surgery not only allows active elbow extension, but also increased the amplitude and strength as well as the speed of arm movement. Finally, the results also point to TROIDS allowing a more pronounced and natural push phase and an improved arm movement pattern during both propulsion and recovery phase under normal and extreme conditions.

It was hypothesized that superparamagnetic nanoparticles encapsulated in a silica shell with a fluorescent dye could be functionalized with axonal tracers and could be used for serial, non-invasive imaging with magnetic resonance imaging (MRI) for axon tract tracing. Nanoparticles functionalized with amine, octadecyl, silica, and biotinylated dextran amine were manufactured and characterized with MRI, scanning electron microscopy, and UV-visible, infrared, and fluorescence spectroscopy. Nanoparticle concentrations of 10 mM were not toxic to adult rat neural progenitor cells (NPCs) and labeled approximately 90% of cells. Nanoparticles were assessed for anterograde and retrograde tract tracing in adult rat models. With MRI and microscopy, the nanoparticles did not appear to trace axons but did provide an MRI signal for up to 3 weeks post implantation. While functionalized nanoparticles did not appear to trace axons, they are not toxic to NPCs and may be used as a MRI contrast agent in the neural axis.

At the author’s request, the abstract has been removed due to the confidential nature of the thesis. It will be added once the embargo period has passed.

Sociologists have only recently paid attention to how men experience physical disability. However, current research continues to ignore how different racial groups experience it. The goal of this study was to examine how black and white men experience life with a physical disability. Using qualitative research techniques involving in-depth, face-to-face interviews with 10 black and 10 white men, I focus on how meanings of disability and masculinity shift after a traumatic injury. Using symbolic interactionism and social construction as theoretical frameworks, I examine how these men formed and modified meanings for disability and masculinity through social interactions. I also analyze the strategies they use to manage a stigmatized identity. Finally, I explore how they negotiate a masculine identity within larger social contexts. My findings suggest that black and white men’s constructions of masculinity and disability are more similar than different on all levels. Furthermore, these men used three strategies to negotiate their new social identities: reinforcing idealized masculinity, modified masculinity, and lost masculinity.