Centre for Neuroscience - Theses
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ItemPain perception and processing in ageing and Alzheimer's disease( 2008)The prevalence of chronic pain is known to increase with advancing age, with over 50% of community dwelling older adults (aged 65 years and over) and up to 80% of those residing in nursing homes estimated to be suffering some form of persistent or recurring pain complaint. In addition to a greater likelihood of pain, advancing age is associated with increased reports of pain interference. It is possible to ascribe age-related changes in pain report and impact to increased disease prevalence and severity in older people. However, there is also evidence that ageing has effects on pain perception, central pain processing, and plasticity of pain responses that are not explained by co-morbid disease. The increased prevalence of chronic pain in older adults represents a major public health concern. As a result of increased life expectancy and the post-World War II baby boom, there will be a dramatic change in the demographic structure of our population over the coming decades, with older adults representing the fastest-growing segment of our communities. The proportion of the total population over the age of 65 in Australia has risen from 9% in 1976, to 12% in 2001, and is predicted to reach 16% by the year 2016. Pain that is undetected or under-treated can adversely affect quality of life for older adults, leading to diminished mood, impaired cognition, behavioural problems, as well as increased functional dependence. This in turn contributes to greater demands for daily personal care and a resultant increase in health-care costs. Pain management is a particularly salient issue in the case of older adults with dementia, who are at increased risk of undetected pain on account of impaired cognition and communication skills. Indeed, clinical reports show that patients with Alzheimer’s disease (AD) are routinely administered fewer pain-relief medications compared with their cognitively-intact peers. Understandably, reports of reduced analgesia in AD have sparked considerable research interest, and over recent years there has been a marked increase in the number of studies aimed at better characterising the experience of pain in patients with AD. However, despite these efforts, the effects of neurodegeneration on pain processing, and the specific ways in which the disease process impacts on brain responses to noxious stimulation and the ensuing experience of pain have not been previously determined. Improved management of pain is fundamental to the clinical care of older adults, particularly those with dementia. However, the potential to adequately counteract pro-nociceptive processes and facilitate endogenous inhibitory mechanisms in the treatment of ongoing pain in older adults will only become possible once the effects of ageing and age-related neurodegeneration on central pain processing are identified and described. The overarching goal of this thesis was therefore to improve current understanding of the ways in which normal ageing and Alzheimer’s disease impact on the perception and central nervous system processing of pain. The findings of this thesis provide valuable new insights into the impact of ageing and AD on the central mechanisms contributing to pain perception, and may therefore contribute toward better management and treatment of pain in this vulnerable and rapidly growing sector of our community. Thesis outline: Chapter 2 provides a review of the background literature and rationale for the thesis. The chapter begins with a discussion of current understanding of pain as a multidimensional phenomenon shaped by sensory, emotional and cognitive components, and leads into a description of neural mechanisms of nociception, as well as the supraspinal processes involved in the elaboration of nociceptive signals into these aspects of pain. The impact of ageing on the structure and function of central nervous system regions underlying these processes are discussed, along with the findings from previous clinical and empirical data which suggest age-related changes in pain perception. Current understanding of the neuropathological and clinical aspects of AD is reviewed, with particular emphasis on potential ways in which the disease may impact on central nociceptive processing and the behavioural response to pain. This is followed by a review of the previous clinical and empirical literature examining pain perception in AD. Finally, the aims of the current thesis are outlined. Chapter 3 describes the general methods which were employed in the subsequent empirical chapters in order to address the aims of the thesis. The equipment and psychophysical procedures used to assess pain perception in healthy young and older adults and patients with AD are described. The basic principals of magnetic resonance imaging (MRI) are then outlined, and the utility of structural and functional MRI for assessing age-related and disease-related changes to brain regions involved in pain perception and processing are discussed. The empirical studies which were undertaken to identify the impact of ageing and AD on central pain processing are presented in the next three chapters. Chapter 4 begins with psychophysical studies comparing sensory and emotional responses to pain in healthy young and older adults, and follows with MRI investigations of age-related differences in brain volumetry and pain-related brain activity. Studies of pain sensitivity and pain-evoked brain activity in patients with AD compared with age-matched controls are presented in Chapter 5. Following on from these findings of AD-related differences in pain-evoked brain activation, the study described in Chapter 6 used functional connectivity analysis in order to assess the impact of AD on the functional integration of brain regions underlying the sensory, emotional, and cognitive aspects of pain. The key findings presented in the preceding three chapters are summarized in a general discussion in Chapter 7. The implications of the findings, in terms of the clinical management of pain in older adults with and without Alzheimer’s disease are discussed. The opportunity is also taken to discuss some of the limitations of the present research, and finally, recommendations are made for future research directions.