Existing research has emphasised the risks to identity as a consequence of chronic pain. However, this line of enquiry has rarely included older people. Therefore, the current thesis aimed to explore qualitatively the role of identity in older people experiencing chronic pain. Correspondingly, the narrative review contained in this thesis elucidates the significance of identity development to later life through the lens of Erikson's theory of development (1980; 1986). It is argued that the framework offered by this theory addresses the limitations of current models of positive aging and places identity development at the heart of these discussions. The research paper that follows describes an Interpretative Phenomenological Analysis of the experiences of seven women aged over 65 with chronic pain. Four interconnected yet distinct themes relating to identity are reported: Adjusting to the disrupted self, the familiar self, self and others, and getting the right amount of help. A number of commonalities with the extant literature as well as connected identity issues related to aging indicated some potential barriers to pain management and optimal adjustment to pain for older people. It is concluded that identity is a relevant and important concept to those experiencing chronic pain at any age and lifespan identity issues need to be considered concurrently. The critical review that follows considers the strengths and limitations of the research paper through reflections on the interview process, the analytical method and process, and ethical dilemmas that arose during the course of the study. Subsequently, some considerations for future research practice are discussed. It is concluded that despite some limitations to the study, this paper underscores some important themes of relevance to older people's adjustment to chronic pain.

Chronic pain is a long-standing condition which impacts upon physical and psychosocial health. Pain management programmes aim to help patients understand and manage their pain to alleviate distress. Alcohol use has been proposed as a complicating factor in the management of pain.This thesis includes a systematic review of the literature on alcohol use in chronic pain which indicates that the use of alcohol has a negative effect on both pain and psychological functioning.

The details of the interactions between steroid honnones and the pain experience are only just beginning to be understood. This thesis uses both behavioural measures and functional magnetic resonance imaging (FMRI) to investigate the relationships between steroid hormones and the response to experimental noxious thennal stimuli of the ann and abdomen. In the first half of this thesis, the hypothesis that central actions of steroid honnones modulate the pain experience by specific interactions with endogenous pain modulatory systems was investigated. As expected, no influence of the menstrual cycle on the perception of noxious stimuli could be demonstrated in healthy women with either naturally controlled cycles or those using the combined oral contraceptive pill (COCP). However, the corre lations of brain activity in response to noxious stimuli and the specific serum honnone levels were in the predicted brain regions, supporting influences of estradiol on opiates; progesterone on y-aminobutyric acid (GABA); and cortisol on the endocannabinoid system. Furthennore, imaging data suggest that the observed increase in sensit ivity to noxious stimuli in the women using the COCP is likely mediated by reduced activ ity of the endogenous opioid system, secondary to low serum estradiol levels. In the second half of this thesis, the hypothesis that repeated episodes of menstruation are associated with long-lasting alterations in the central processing of noxious stimuli was addressed. In agreement with this hypothesis, dysmenorrhoea was associated with an increase in sensitivity to noxious stimulation of both sites, that persisted beyond the time of menstruation. Negative correlations between the duration of symptoms and both brain activity in response to the stimuli and serum cortisol levels suggest the development of a maladaptive response to repeated episodes of pain. However, when comparing healthy, pain-free male and female subjects, corre lations with age were only observed in female subjects and only in response to abdominal stimuli, suggesting the development of an adaptive response to menstruation in painfree women. This

Chronic pain is described as pain that persists beyond the time we would expect normal healing to occur, usually beyond three months for most tissue. Chronic pain is associated with increased prevalence of psychological symptoms. Despite high prevalence rates of mood disorders among those who are affected. by chronic pain, most estimates indicate that the majority of people do not experience clinically significant symptoms and adjust to the stresses associated with the condition. This observation has given rise to hypotheses about psychological factors that may mediate the effect of a chronic stressor such as chronic pain, on subjective well-being. Meaning refers to an individual's understanding of the implications a chronic health condition has on self, relationships with others, priorities, and future goals. Research has indicated that the presence of meaning is associated with lower levels of anxiety and depression amongst those who are affected by a chronic health condition. The aim of the study was to investigate the relationship between meaning, chronic pain, distress, well-being and pain-related cognitions in a sample of participants who were experiencing chronic pain. 74 participants, attending two Outpatient Pain Management and Physiotherapy Clinics, completed measures of pain severity, interference, meaning in life, well-being, pain-related cognitions, and distress. Findings indicated a significant association between pain interference, and psychological distress, as well as between pain interference, well-being and the integration of meaning. Unlike pain interference, pain severity was not found to be significantly related either to presence of meaning or to absence of search for· meaning. Findings also indicated that integration of meaning moderated the relationship between pain interference and distress, even after 3 taking into account the impact of pain-related cognitions on levels of psychological distress. Contrary to predictions, absence of search for meaning was not found to mediate the relationship between these variables. Overall, findings indicated that meaning has a significant impact on how well people adjust to experiencing chronic pain, even after pain-related cognitions are taken into account. Theoretical and clinical implications as well as strengths and limitations of the study are discussed.

This ethnographic study explores how children's pain is managed in the context of a general paediatric ward. Fieldwork was conducted on one ward over a period of 11 months. Data were collected using observations and informal interviews. Children (n=5) aged 8-16 years, their mothers (n=4) and nurses (n=5) participated in in-depth interviews exploring understandings and experiences of pain and pain management. A symbolic interactionist stance was taken, using the key concepts of pain work and the ceremonial order of the ward. In the context of the ward, pain is a eo-constructed phenomenon, incorporating the perspectives, interpretations and interactions of those involved. Nurses drew on expected and unexpected trajectories and their interactions with children to construct pain as a working or 'clinical' entity. They conceptualised pain in three main ways; routine/normal pain, fear as pain and complex pain. Children's accounts of pain revealed how pain was interpreted using temporal and causal dimensions with their mothers being central to their experiences of pain management. Mothers also drew on causal and temporal dimensions to interpret pain, contextualising this in their knowledge of their child. Nurses carried out various forms of work which served to sustain the ceremonial order ofthe ward. This included pain work, identity work, and emotion work. Pain work was also negotiated by nurses within the wider social context of the ward, showing how the division of labour, spatio-ternporal features, and the social organisation of the ward shaped pain management practices. The key findings taken together reveal multiple conceptualisations of pain at work, and multiple dynamics of interaction, in which nurses play a pivotal role. This thesis therefore develops new understandings of children's pain and pain management in using an ethnographic approach, and by applying sociological concepts to develop an integrated and theorised analysis of acute pain management on a paediatric ward.

Chronic joint pain, specifically knee pain, is a prevalent disabling chronic condition. Policy and clinical guidelines promote education of risk factors and supported self-management to ameliorate predicted demands upon state, society and the individual. Extant literature offers little insight into if and how 'risk' is understood in relation to chronic joint pain. The broad research questions in this thesis ask: do people have knowledge of risk factors for joint pain? How do people conceptualise or experience risk in relation to joint pain? How does risk relate to self-management? Qualitative methodology is used within this study. An interpretive approach is used to explore and understand participants sense making and experiences in relation to the concept of risk. Fifteen participants took part in two in-depth interviews spaced six months apart. Eight of the participants also took part in a diary study between the interviews. Findings reveal that lay explanations about jOint pain, lived experiences of illness, meaning making about the body and subsequent learned strategies to deal with joint pain mirror clinical perspectives of 'risk'. People with joint pain encounter 'risk' as a threat to biography or as hazardous scenarios related to their social environment. Self-management of symptoms is mediated by subjective and socio-contextual factors relating to embodied experiences of pain and lay sense making about how physiology interacts with motion and weight loss. Self-management in relation to 'risk' is about managing threats to self, obligations to others, and hazardous scenarios as well as symptom control. New insights for understanding risk are suggested, taking into account the epistemological, ontological and material elements of people's lives with chronic joint pain.

Acute pain plays a fundamental role in survival, providing protection from potentially damaging stimuli. However, chronic pain is much less useful and is hugely detrimental to quality of life. An inadequately low number of chronic pain patients get meaningful analgesic treatment benefit, and very few novel analgesics have become available in recent years. This is due in part to a high failure rate of new analgesics in early clinical trials. with a significant number of these failures being due to lack of efficacy, thus questioning whether current animal models, and/or how pain is assessed in these models, sufficiently predict clinical efficacy. Development of translational pain models will bridge this gap between preclinical animal and human clinical research by providing experimental models that have similar underlying mechanisms. Additionally. use of translational objective measures of pain as pharmocodynamic endpoints will aid drug development. The work described in this thesis aimed to address these two critical issues, namely that animal and human pain models are often mechanistically different and are quantified using different outcome measures. The main focus of this project was translational inflammatory pain models with a central sensitisation component, a cardinal clinical feature or chronic pain. As secondary mechanical hyperalgesia results from central sensitisation. the work focused on development of models ill which secondary mechanical hyperalgesia is exhibited, combined with objective assessment of this mechanical hyperalgesia. The key findings of this project were two-fold. Firstly, a novel objective neurophysiological measure of mechanical pain was developed and validated in healthy human volunteers. Secondly, the occurrence of secondary mechanical hyperalgesia was investigated in an established translational inflammatory pain model in the rat (the ultraviolet-B (UV -13) model). and in a novel model which combines UV-B with heat rekindling to prolong central sensitisation. Finally. to bring the two aspects of the project together. the objective measure of mechanical pain in humans was used to investigate secondary mechanical hyperalgesia in a translational experimental inflammatory pain model in healthy human volunteers. The development of translational experimental models of inflammatory pain. with emphasis on the clinically relevant phenomenon of central sensitisation, will improve transition of novel analgesics into the clinic. The objective measure of mechanical pain in humans described here is a neurophysiological technique that will aid future pain research when used alongside subjective measures of pain, creating a multidimensional approach to pain assessment. It also has the potential to be back-translated to the laboratory rat for future quantification of secondary mechanical hyperalgesia and central sensitisation ill translational models such as the UV-B model.

Injury is detected by a population of sensory nerves called nociceptors. Nociceptor sensitisation enhances pain and serves as a protective mechanism which promotes recovery. However, pain can become chronic. When this occurs pain becomes pathological in its own right and has extremely deleterious effects on the patient. A fuller understanding of the mechanisms by which nociceptors become sensitised and detect physiological stimuli is required to better treat chronic pain.

Research has found that some individuals magnify their symptoms. This study investigated the psychometric properties of a new questionnaire, the Personal Problems Questionnaire (PPQ), which aims to screen for cognitive, emotional and physical symptoms and identify patients who present with non-valid symptoms, flagging up the need for a more comprehensive assessment. Demographic data were collected from 77 participants with chronic pain. The PPQ was administered alongside the Short Form McGill Pain Questionnaire (SFMPQ; Melzak, 1987) and the Medical Symptom Validity Test (MSVT; Green, 2004), a brief test of effort. A subsample (27 participants) also completed the Personality Assessment Inventory (PAl; Morey, 2007). Additionally, secondary analysis was performed on the sample of 410 healthy community participants used for the norming of the PPQ to explore its scales' underlying factors and internal reliability. Separate exploratory factor analyses on the PPQ scales in the clinical and healthy controls norming samples identified two factors. The internal reliability of the scales of the PPQ was good in the chronic pain sample (a > 0.80) and in the healthy norming community sample (all scales except for the Neurological Symptoms scale a > 0.70). Concurrent validity for several clinical and for all the validity scales of the PPQ was supported by exploring their association with the PAl, SF-MPQ and MSVT. Furthermore, the PPQ Non-Valid Physical Scale was able to predict mean MSVT score. Sensitivity and specificity of PPQ validity scales were calculated using the cut-off derived from the simulation study and the MSVT as reference criterion. The PPQ is the first British-developed self-report questionnaire that includes a measure of symptom validity. The results of this study suggest that the PPQ holds promise as a screening tool for emotional, physical and cognitive symptoms.

Despite extensive study of the pathophysiology, pain states still represent a significant unmet clinical need. Spinal hyper- excitability is a key feature of acute and chronic pain states, yet the underlying mechanisms are incompletely understood. To this end, the aim of this thesis was to examine the effects of modulation of the spinal cannabinoid and vanilloid receptor systems in rat models of acute and chronic pain. Anti-nociceptive effects of inhibiting spinal cord endocannabinoid (EC) catabolism were investigated. In naive rats, spinal administration of the novel MAGL inhibitor JZL184 (25-100 μg) produced a robust, dose-dependent inhibition of noxious mechanically-evoked (15-26 g) responses of WDR neurones, probably via a CB1 receptor-mediated mechanism. Spinal JZL184 (100 μg) also ablated the expansion of 'WDR receptive fields, a marker of central hyper-excitability, following intra-plantar administration of carrageenan (2 mg/l00 μL). Ex vivo analyses failed to demonstrate the expected concomitant elevation of 2- AG and inhibition of MAGL in whole lumbar spinal cord homogenates. However, in vitro studies confirmed potent inhibition of MAGL by JZL184 (IC50 = 76 - 287 nM in spinal cord), suggesting the effects of this compound are indeed mediated by 2-AG/CB1. Gross tissue analyses may, therefore, be insufficiently sensitive to detect biologically significant local fluctuations in EC signalling. Interestingly, these experiments also revealed substantial heterogeneity of monoglyceride hydrolytic activity in rodent CNS fractions. The involvement of the spinal EC system in both rapid and sustained spinal plasticity in pain states was also assessed. Levels of EC-related molecules, genes, and proteins were measured in spinal cord tissue in the carrageenan model of acute inflammatory pain and the monosodium iodoacetate (MIA) model of chronic joint pain. Significant elevations in AEA were demonstrated in both models, whilst significant increases in DEA, PEA, and 2-AG were observed in the MIA model only. Analysis of gene and protein expression levels suggest the early alterations may be mediated by decreased catabolism, whilst later increases were driven by increased synthesis. Finally, spinal TRPV1 receptors were assessed as a therapeutic target in the MIA model. Substantial progressive increases in spinal TRPV1 expression were demonstrated from post-induction day 14 to 28 following unilateral intra-articular injection of 1mg MIA. These increases were partially correlated with the development of distal allodynia and knee joint pathology, suggesting a role for these receptors in the development of spinal hyper-excitability in this model. Spinal administration of the TRPV1 antagonist JNJ-17203212 (18.75 - 75 μg) produced dose-dependent inhibition of noxious mechanically-evoked responses of WDR neurones to a similar extent in both saline- and MIA-treated rats. However, efficacy of the mid-range dose was positively correlated with the level of spinal TRPV1 expression. These data demonstrate the anti-nociceptive efficacy of modulating the EC and TRPV1 signalling systems. However, the substantial plasticity of these systems demonstrated in nociceptive states warrants further investigation, and may have significant bearing on the future success of such therapeutic approaches.