As a major public health problem affecting more that 76.5 million Americans, chronic pain is one main reason why people seek medical attention. It is a pathological nervous system disorder that persists for months or years. Sensitization of nociceptive neurons in the dorsal horn of the spinal cord is crucial in the development of allodynia and hyperalgesia. The work presented in this thesis will focus on spinal protein kinase M zeta (PKMζ)-mediated plasticity and GABAergic disinhibition as spinal amplification mechanisms that orchestrate persistent changes in the dorsal horn of the spinal cord. As a result of central sensitization following peripheral nerve injruy, GABAergic disinhibition occurs due to an alteration in Cl- homeostasis via reduced KCC2 expression and function. Intrathecal administration of acetazolamide (ACT), a carbonic anhydrase inhibitor, attenuated neuropathic allodynia and spinal co-adminitation of ACT and midazolam (MZL), an allosteric modulator of the benzodiazepine class of GABAA receptors, synergistically inhibited neuropathic allodynia. Further studies concerning the impact of altered Cl-homeostasis via reduced KCC2-mediated Cl-extrusion capacity on the analgesic efficacy and potency of GABAA receptor agonist and allosteric modulators revealed that there is a differential regulation of the agonists and allosteric modulators at the GABAA receptor complex when Cl-homeostasis is altered. Another spinal amplification mechanism leading to central sensitization is PKMζ-mediated spinal LTP. In model of persistent nociceptive sensitization, allodynia induced by IL-6 injection or plantar incision was abolished by both the inhibition of protein translation machinery and PKMζ inhibitor, ZIP. However, only PKMζ inhibition prevented the enhanced pain hypersensitivity precipitated by a subsequent stimulus after the initial hypersensitivity had resolved, asserting that spinal PKMζ underlies the maintenance mechanisms of persistent nociceptive sensitization. Also, these results confirmed that the initiation mechanisms of persistent sensitization parallel LTP initiation mechanisms and the maintenance mechanisms of persistent sensitization parallel LTP maintenance mechanisms. Taken together, these results indicate that these amplification mechanisms drive a chronic persistent state in these models such that inhibition of these spinal amplication mechanisms will serve as an effective approach in the quenching chronic pain hypersensitivity in chronic pain models.

This study investigated the hypothesis that dietary compliance among hemodialysis patients is related to their health locus of control orientation, as well as other factors. Fifty chronic hemodialysis patients were studied over a 3-month period. Among women interdialytic weight gain as a percentage of body weight (%BWG) was positively correlated with the number of weekly hemodialysis sessions and negatively related to ease of fluid compliance. Among men %BWG was positively correlated with powerful others health locus of control, family support, and hemodialysis tenure, and negatively correlated with employment. The best fitting multiple regression equation explained 26% of the variance for %BWG using ease of fluid compliance, frequency of urination, and powerful others orientation, with sex effects seen for the latter two variables. Staff perceptions of patient dietary compliance were also highly correlated with %BWG, though they never tabulated fluid gain controlled for body weight.

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Chronic pain is recognized for its intra- and interpersonal stress, with greater social support being associated with better patient outcomes. Urologic Chronic Pelvic Pain Syndromes (UCPPS) are pain-associated conditions that are prevalent across genders and are strongly associated with diminished quality of life (QOL). To date, no gender-based research has examined such supportive behaviours in UCPPS samples. One model, the stress-buffering model of social support, suggests people with greater support within their proximal (e.g., marriage) and distal (e.g., physician) social environment may be protected from negative stressor impact (i.e., pain). Due to their strong associations with poorer QoL, I hypothesized catastrophizing and perceived pain control as important intrapersonal cognitive variables to also consider in such relations between pain and patient QoL. In this dissertation, I examined several research questions using two self-report studies: 1) Are there gender differences in social support for people with UCPPS?; 2) Does social support moderate the relationship between pain and patient outcome variables and are there gender differences in this effect?; and 3) If social support moderates the relationship between pain and outcomes, is this effect further moderated by cognitive variables and/or gender? In Studies 1 and 2, women with IC/PBS endorsed higher levels of solicitous and distracting spouse responses to pain behaviour than did men with CP/CPPS. Additionally, in Study 2 women reported greater support from friends than did men. In regard to moderation effects in Study 1, distracting spouse responses buffered the relationships between patient pain and mental QoL, and between pain and disability. However, spouse solicitousness had a detrimental effect on the relationship between patient pain and mental QoL but only at low levels of catastrophizing in the patient. The genders did not differ in the effect of spouse responses to pain behaviour in Study 1, and Study 1 results with respect to the stress-buffering role of distracting spouse responses were not replicated in Study 2. In Study 2, sources of social support from outside of the marriage also did not have a stress-buffering effect on the relationship between pain and patient outcome. Of the models reviewed, no one current model for understanding the role of social support or catastrophizing in chronic pain was sufficient to account for the findings reported in these studies. However, a dyadic emotion regulation perspective is suggested with implications for marital therapy with couples with chronic pain. / Thesis (Ph.D, Psychology) -- Queen's University, 2013-11-18 19:17:11.276

Muscle wasting and increased proteolysis is a major problem in chronic kidney disease (CKD). Exercise is potentially beneficial, but has been under-investigated in pre-dialysis CKD and could theoretically worsen acidosis through exercise-induced lactic acid generation. We therefore investigated effects of 6 months walking exercise with and without additional alkali therapy. 40 patients were recruited (23 male and 17 female, median age 58, range 20-83, mean eGFR±SEM 25.7±1.2ml/min/1.73m2). 20 undertook walking exercise at a Borg Rating of Perceived Exertion Rate (RPE) of 12-14 for at least 30 minutes, 5 times a week. The other 20 continued with normal physical activity (non-exercising controls). In addition to standard oral bicarbonate therapy (STD), 10 patients in each group were randomised to receive additional bicarbonate (XS). Blood and vastus lateralis muscle biopsies were drawn at baseline, one and six months. 18 exercisers (including 8 in XS group) and 14 controls (6 in XS group) completed the 6 month study. Exercise tolerance increased after 1 and 6 months in the exercisers, but not the controls, accompanied by a reduced acute lactate response in the XS, but not the STD exercising group. After 6 months of exercise, 9 intramuscular free amino acids showed striking depletion in the STD, but not XS bicarbonate group. This suggests an inhibition of active amino acid transporters, possibly the SNAT2 transporters that are inhibited by acidosis. Studies with cultured myotubes identified glucocorticoid as a possible mediator of acid s inhibitory effect on SNAT2. The preservation of amino acid concentrations in the XS exercising group was accompanied by strong suppression of ubiquitin E3-ligases MuRF-1 and MAFbx which activate proteolysis through the ubiquitin-proteasome pathway. However, other anabolic indicators (Protein Kinase B activation and suppression of the 14kDa actin fragment) were unaffected in the exercising XS group. Possibly because of this, overall suppression of myofibrillar proteolysis (3-methyl histidine excretion) and increased lean body mass (DEXA) were not observed in the exercising patients. As XS alkali had no effect in non-exercisers, it is concluded that alkali effects in the exercisers arose by countering exercise-induced acidosis. Sulphuric acid produced from the catabolism of sulphur-containing amino acids ingested in the diet is the main contributor to the daily titratable acid load and hence acidosis in CKD. In these patients the amount of sulphate excreted in urine over 24h varied widely between individuals. This directly correlated with 3-methyl histidine excretion suggesting that sulphate excretion may be a better clinical indicator of acidotic patients at long-term risk of cachexia than conventional measures such as venous bicarbonate. Studies with cultured myotubes confirmed that skeletal muscle is a source of sulphuric acid and showed that production of this acid is partly suppressed by L-Glutamine a potential novel way to control acidosis in CKD.

This thesis explores doctors’ and medical students’ attitudes toward older patients in UK hospital settings. There have been regular and strong assertions in the grey literature and the news media that negative attitudes toward older patients may contribute to the inequality of healthcare service provision and treatment for older patients, compared to younger patients (those aged under 65 years), in UK hospital settings. However, much of the evidence does not investigate or explore these attitudes using a theoretical framework of attitudes outlined in the scientific research literature. This thesis comprises three studies. Firstly, a systematic search and review (Study 1) was undertaken in order to determine how attitudes toward older patients had been explored to date in the English-language, scientific research literature. Results demonstrated that previous studies had focused on attitude measurement rather than exploring the content of attitudes toward older patients. In fact, there was little evidence that previous research had ever explored these attitudes, despite the number of studies attempting to measure them. Furthermore, the review indicated the lack of research emanating from UK settings. In Study 2, attitudes toward older patients and their care were explored in twenty-five in-depth interviews with medical students and doctors in a UK NHS Hospital trust. Data were thematically analysed and findings indicated that attitudes toward older patients and their care could be conceptualised as: (1) attitudes toward older patients and their healthcare needs, and (2) attitudes toward providing care for older patients (e.g. the social and organisational barriers and facilitators). Within these two domains, the themes, subthemes and nodes, which represent attitude content with increasing levels of specificity, are presented. The findings from Study 2 mark one of the first attempts in this research area to explore and describe the content of attitudes in line with a theoretical framework of attitudes. The final study, Study 3, explored the devaluation and unpopularity of the specialty of geriatric medicine as a future career choice in a sample of junior doctors. Having identified, in Study 2, that geriatric medicine was not highly regarded in a range of doctors and medical students, Study 3 aimed to ascertain whether this was due to the organisational and working environment or due to older patient-related factors in a recently-qualified sample of doctors. The findings indicated that organisational and work-related factors serve to discourage junior doctors from pursuing geriatric medicine, rather than factors related to the older patients treated on geriatric wards. This thesis contributes to the research literature in two main ways. Firstly, this thesis outlines the research gaps in the worldwide English-language scientific research. Secondly, this thesis presents a conceptualisation of doctors’ and medical students’ attitudes toward older patients in a UK hospital setting. Importantly, this conceptualisation provides research that is relevant to UK settings and is in line with a theoretical framework of attitudes that has been identified from the scientific research literature. The strengths and limitations of this work are discussed.

This thesis consists of two sections, the first of which is a systematic review of selfreport measures of mindfulness. The review aims were to evaluate the psychometric properties of each of the identified measures and examine their utility for research and clinical practice. Definitions of mindfulness were central to the differences found between measures, and as such this review also provides an overview of how mindfulness has been conceptualised in the literature. This review has been presented in the format required by the journal, Clinical Psychology Review. The second section is a meta-analysis which examines the efficacy of mindfulnessbased stress reduction (MBSR). Mindfulness-based interventions are increasingly being applied in a range of settings and the evidence base is growing. Specifically, this review aimed to determine the effectiveness of MBSR on quality of life for people suffering from chronic physical health conditions. The methods and results of the meta-analysis are described in detail, followed by a discussion of the findings. A more concise overview is then provided as a journal article, in the format required by the British Journal of Clinical Psychology. The guidelines for submission to both journals are included in Appendix 1 and 2 respectively.

Background: Psychological research has consistently demonstrated the importance of cognitions in the form of thoughts and images on an individual’s wellbeing. Having pain-related verbal cognitions has been shown to lead to poorer outcomes for patients (McCracken & Turk, 2002). Research in other conditions has shown mental images have a more powerful impact on emotion than verbal cognitions (Holmes & Matthews, 2005). To date however, little work has explored the role of mental imagery in adjustment to chronic pain. Methods Fourteen semi-structured interviews were conducted with individuals with chronic pain. Interview transcripts were analysed according to grounded theory methods to construct a substantive theory of the impact spontaneously-invoked images of pain have on functioning. Results Eight participants reported pain-related imagery and three reported mental images associated with related symptoms. In line with previous findings (Gillanders et al., 2012; Gosden, 2008) the frequency and intensity of pain-related images influenced the degree of distress experienced. There was a distinction made between intrusive mental images and visual descriptions or metaphors of pain. The former being conceptualised as a visual cognition and playing a role in the aetiology and maintenance of distress in chronic pain and therefore an adverse impact on functioning. Conclusion Enhancing our understanding of pain related imagery and its impact on functioning could inform the design of interventions in clinical practice. Working systematically with patients’ idiosyncratic pain related images and the beliefs that are associated with them could be a helpful specific target for therapy.

This thesis explores Turkish migrants’ practices of diabetes care in Germany. Health statistics frequently identify minority groups as vulnerable to chronic illness and Turkish-origin Germans are said to be more likely to suffer from type 2 diabetes than Germans or Turks in Turkey. Anthropological studies on marginal population groups with diabetes explore experiences of social suffering and inequality that influence such high illness prevalence, or investigate how conflictual lay beliefs and medical encounters affect illness care. Those studies that analyse active diabetes patient and healthcare practices concentrate on the majority population. Drawing on ethnographic fieldwork in Berlin from September 2006 to September 2007, this thesis examines how Turkish Berliners actively engage in diabetes care, and thus joins two themes seldom connected: illness practices and marginality. Initial interviews with healthcare professionals alluded to a Turkish migrant patient group living in deprivation and immobilised by high illiteracy rates, lacking language skills and health knowledge. Despite such experience of marginality, ethnographic exploration revealed that informal diabetes care, for example through a Turkishlanguage self-help group, is nonetheless individually and collectively negotiated where formal care is inadequate. On the one hand, the thesis investigates practices of diabetes control in learning, monitoring and manoeuvring diabetes. Rather than representing the common image of the inert, disadvantaged migrant patient, Turkish Berliners of the self-help group engage in deliberate “tactics of diabetes control” to make their chronic illness experience habitable. On the other hand, the thesis explores how “diabetes among Turkish-origin Berliners” can be a form of sociality, political activism and economic enterprise that involves many social actors not only patients and their healthcare professionals, in order to fill a provision gap.