Arsenic is a metalloid present throughout the world, and the primary sources of exposure are through air, soil, and water. Arsenic is currently ranked as the most hazardous substance among environmental toxicants, and is well recognized as a human carcinogen, as well as a contributor to metabolic and cardiovascular diseases. However, cardiovascular effects have been mostly evaluated in epidemiological studies, and the direct mechanisms of pathogenesis remain largely unknown. The scope of studies described in this dissertation characterizes the cardiovascular pathophysiology associated with exposure to environmentally-relevant arsenic concentrations (100 µg/L), and attempts to elucidate the molecular mechanisms behind impaired vascular function. The effects of chronic arsenic exposure on blood pressure regulation were examined using a mouse model exposed to 100 µg/L for 22 weeks. Chronic exposure to arsenic results in the development of hypertension and concentric left ventricular hypertrophy. Furthermore, data presented here demonstrates that in utero exposure contributes to the development of metabolic syndrome throughout adulthood. Results indicate the development of hyperglycemia, hypercholesterolemia and nonalcoholic fatty liver disease. Mechanistic studies demonstrate the effects of arsenicals on endothelial nitric oxide synthase (eNOS) and its role in arsenic-induced vascular relaxation impairment. Biochemical assessment of eNOS conclude that decreased nitric oxide availability does not occur through alterations in protein levels or phosphorylation changes; however, decreased activity is likely a result of protein dimer stability through alterations in zinc tetrathiolate binding.

This thesis discusses the illness experience of people living with chronic pain resulting from Temporomandibular disorders (TMD). The literature discusses various aspects of the experience of chronic pain, but there is little research reported specifically on the experience of living with TMD. Using analysis of sufferers' narratives, I discuss common explanatory models and coping strategies. I then present aspects of the bodily experience of TMD as seen in people with comorbid illnesses. The personal or mental aspects of TMD are explored, particularly in terms of fear, anxiety, and hope for the future. Lastly, the broader impacts of TMD are explored through sufferers' relationships with friends and family, and sufferers' ability to function in social contexts. It is concluded that TMD impacts many areas of sufferers' lives, and that the lived experience extends beyond diagnosis and treatment seeking to include the day to day management of TMD pain.

This study aimed to examine whether trigeminal nerve injury induces chronic nociceptive behaviour and central sensitization (CS) in functionally identified medullary dorsal horn (MDH) nociceptive neurons in mice, and whether CS in acute and chronic orofacial pain models and nociceptive behaviour in the chronic model are affected by systemic administration of pregabalin. Infraorbital nerve injury induced chronic facial mechanical allodynia as well as MDH CS; acute noxious tooth pulp stimulation also induced MDS CS. Systemic administration of pregabalin attenuated the nerve injury-induced allodynia as well as the MDH CS in both the chronic and acute pain models. These findings reveal that MDH CS occurs in mouse models of acute and chronic orofacial pain and that pregabalin may prove useful clinically in acute and chronic orofacial pain states.

This study aimed to examine whether trigeminal nerve injury induces chronic nociceptive behaviour and central sensitization (CS) in functionally identified medullary dorsal horn (MDH) nociceptive neurons in mice, and whether CS in acute and chronic orofacial pain models and nociceptive behaviour in the chronic model are affected by systemic administration of pregabalin. Infraorbital nerve injury induced chronic facial mechanical allodynia as well as MDH CS; acute noxious tooth pulp stimulation also induced MDS CS. Systemic administration of pregabalin attenuated the nerve injury-induced allodynia as well as the MDH CS in both the chronic and acute pain models. These findings reveal that MDH CS occurs in mouse models of acute and chronic orofacial pain and that pregabalin may prove useful clinically in acute and chronic orofacial pain states.

Background: Chronic obstructive pulmonary disease (COPD) is a devastating illness that affects 4.3% of the population of British Columbia over the age of 45 years. Asthma is known to coexist in 10-20% of individuals with obstructive lung disease, and adds to the substantial burden of illness posed by COPD alone. Inhaled corticosteroids (ICS) are currently recommended for the management of COPD among individuals with frequent exacerbations; however, the ability of inhaled corticosteroids to reduce death and hospitalizations among individuals with COPD is controversial. Less is known about the effectiveness of ICS among individuals who are afflicted with both COPD and asthma. Methods: We used a retrospective cohort study design and administrative data to estimate the relative effectiveness of ICS in reducing hospitalizations or death among individuals with concomitant asthma and COPD, compared with individuals with COPD alone. We used an extended Cox model to estimate this association, with a time-varying measure of exposure to ICS. Results: We did not find any association between ICS and hazard of death or hospitalization among individuals with COPD alone (HR = 0.99; 95% CI: 0.94 – 1.05), however the hazard was 18% lower (HR = 0.82; 95% CI: 0.69-0.99) among individuals with concomitant disease. Conclusions: Individuals with combined COPD and asthma show significant benefit from the use of ICS and are more responsive to the effects of ICS than individuals with COPD alone.

Exposure to chronic hypoxia (CH) leads to ventilatory acclimatisation to hypoxia (VAH) which is a time-dependent increase in breathing. This study examined the role of the GABAA receptor in establishing VAH. Rats were exposed to CH or control (normoxic) conditions for 10 days during which the GABAA receptor antagonist, bicuculline, was infused systemically or directly into the nucleus of the solitary tract (NTS). Acute breathing trials were then performed to measure resting ventilation and ventilatory chemoreflexes. Systemic administration of bicuculline caused reductions in breathing during acute hypoxia and acute hypercapnia in the control but not the CH animals. Continuous infusion of bicuculline in to the NTS caused a reduction in the acute hypoxic ventilatory response in animals exposed to CH but not in the control animals. The results indicate that exposure to CH alters the GABAA-mediated regulation of acute ventilatory chemoreflexes both in the NTS and elsewhere in the brain.

Wound-related pain is complex, integrating the experience of noncyclic acute wound pain, cyclic acute wound pain, and chronic wound pain (Krasner 1995). More than 80% of chronic wound patients report pain during wound dressing change. A constellation of physical and psychological factors may be involved in the mediation of pain during wound dressing change. A burgeoning body of evidence suggests the intricate relationship between anxiety and pain. In this study, the attachment framework was examined to determine how personal views of self (attachment anxiety) and others (attachment avoidance) may affect pain during dressing change. Attachment styles are systematic patterns of expectations, emotional reactivity, strategies for distress management and social behaviour that are based on an individual’s belief about the self and others. Internal working models are cognitive-affective schemas that guide the attachment patterns. Purpose: The purpose of this study was to explore the relationship of attachment style and pain during dressing change in an older population. In particular the study focussed on the role that anxiety, anticipatory self reported pain, and behavioural expression of pain play in this relationships. Method: A questionnaire was used in this cross-sectional study to classify 96 older subjects into four different categories of attachment styles. Subjects were asked to rate their levels of anticipatory pain and actual pain levels at different times during wound care using a numerical rating scale. Results: The results indicated that subjects experienced more pain during dressing change than at baseline. Secure subjects reported less pain and anxiety than subjects with other attachment styles. Results of regression analysis indicated that anxiety mediated the relationship between attachment and pain. Conclusion: The results of this study also support the role that attachment plays in the experience of pain in older adults. Clinicians must be cognizant of the impact of personality, anxiety, and anticipation of pain on the actual pain experience.

Complex and chronic health conditions with multiple diagnoses and lacking in clinical practice guidelines often require a multidisciplinary care management scheme. Research has shown that the domain knowledge for these conditions is multidisciplinary, inconsistent, nonstandardized and poorly categorized making them heterogeneous and consequently challenging for collaborative work. The application of the boundary objects approach has come to the forefront as a way of closing communication gaps in collaborative work. There are limited research efforts in the application of boundary objects in the health care field and almost none in the area of complex chronic conditions. Research investigation of the application of boundary objects in heterogeneous domains is also limited. The primary objective(s) of this thesis is (are) to develop, test and evaluate a model and a methodology for creating boundary objects in the heterogeneous domain of complex chronic conditions. The methodology in this research applies a two-staged approach for enabling interoperability in the domain. The first stage is the development of a controlled vocabulary as a boundary object and the second stage of the two-staged approach is the development of an ontology as a boundary object to generate syntactic, semantic and pragmatic levels of interoperability in the dynamic domain. Towards these objectives, the boundary objects developed in the study satisfy certain unique requirements, namely to, have pragmatic boundaries, be dynamic in nature and be in standardized forms. To the best of our knowledge, this research is the first to investigate the development of boundary objects in the heterogeneous domain of complex chronic conditions. The outcome of this research is the development of a model for the generation of boundary objects to enhance communication among multidisciplinary clinicians. The model is developed in the heterogeneous domain of two complex chronic health conditions, namely, multiple chemical sensitivity and chronic pain. A testing and an evaluation process conducted in this research demonstrates that a high percentage of clinicians (>80%) agree on the overall usefulness of the boundary objects developed in this research. The results from the research are promising in terms of the potential applications of boundary objects in closing communication gaps in the multidisciplinary management of complex conditions.

In Canada, 3,300 children under the age of 20 are living with Crohn’s Disease (CD) (Crohn’s and Colitis Foundation of Canada, 2008). When an illness such as CD occurs in adolescence, the challenges associated with it are further compounded by the developmental tasks associated with this life stage. The purpose of this study was to understand how adolescents experience living with CD; to explore the impact of disease activity on their quality of life (QOL) and the strategies utilized to maintain and improve their QOL. Using a resiliency framework and narrative inquiry as a research methodology, seven adolescents were interviewed. The results include seven individual stories exemplifying their experiences, and from the stories shared, four patterns emerged: (1) Unconditional Support, (2) Embracing and Accepting Differences, (3) Attitudes and Personal Beliefs and (4) Daily Coping Strategies. These findings may have relevance for health professionals and families and adolescents with CD.

The use of prescription opioids for chronic non-cancer pain is complex. Opioids have the potential to alleviate discomfort and increase ones overall ability to function but, long term use also has potential physical and psychological impacts. The purpose of this study was to explore the lived experience of adults who use prescription opioids to manage chronic non-cancer pain. Nine participants were recruited and interviewed. Participants were asked to describe how using prescription opioids had affected their lives. Interviews were recorded, transcribed and analyzed thematically using Interpretative phenomenological analysis (IPA). Eight themes emerged from the data: the process of decision making, physical effects of using opioids, social consequences of using opioids, Guilt, fears, ambivalence, self-protection, and acceptance. Using opioids made pain more manageable and improved function for most of the participants. Nevertheless, using opioids was also associated with stigma, guilt, fears and ambivalence about their future as persons with chronic pain.