Doctor of Philosophy / Despite the demonstrated efficacy of cognitive-behavioural therapy for chronic pain, recent research has attempted to identify predictors of treatment outcome in order to improve the effectiveness of such treatments. This research has indicated that variables such as the nature of the onset of the pain and psychopathology are associated with poor adjustment to chronic pain. Accordingly, these variables might also be predictive of poor response to treatment. Individuals who experience a sudden onset of pain following an injury or accident, particularly when the instigating event is experienced as psychologically traumatic, may present for treatment with high levels of distress, including symptoms consistent with a posttraumatic stress response. The impact of this type of onset of pain and posttraumatic stress symptoms on adjustment to chronic pain and treatment outcome is the focus of this thesis. Three studies were conducted to clarify and extend earlier research findings in this area. Using 536 patients referred for treatment in a tertiary referral pain management centre, the first study examined the psychometric properties of a widely used self-report measure of posttraumatic stress symptoms (the PTSD Checklist, or PCL), modified for use in a chronic pain sample. This study provided preliminary support for the suitability of the PCL as a self-report measure of Posttraumatic Stress Disorder (PTSD) symptoms in chronic pain patients. However, the study also highlighted a number of issues with the use of self-report measures of posttraumatic stress symptoms in chronic pain patient samples. In particular, PCL items enquiring about symptoms which are a common aspect of the chronic pain experience (e.g. irritability, sleep problems) appeared to contribute to high mean scores on the PCL Avoidance and Arousal subscales. Furthermore, application of diagnostic cut-off scores and an algorithm recommended for the PCL in other trauma groups suggested that a much larger proportion of the sample was identified as potentially meeting diagnostic criteria for PTSD than would have been expected from previous research. The second study utilised the modified PCL to investigate the impact of different types of onset of pain (e.g. traumatic onset) and posttraumatic stress symptoms on adjustment to chronic pain in a sample of 196 chronic pain patients referred to the same centre. For patients who experienced the onset of pain related to a specific event, two independent experts in the field of PTSD determined whether these events satisfied the definition of a traumatic event according to DSM-IV diagnostic criteria. Adjustment was assessed through a number of validated measures of mood, disability, pain experience, and pain-related cognitions. Contrary to expectations, comparisons between patients who had experienced different types of onset of pain revealed few significant differences between them. That is, analyses comparing patients presenting with accident-related pain, or pain related to other specific events, to patients who had experienced spontaneous or insidious onset of pain revealed no significant differences between the groups on measures of pain severity, pain-related disability, and symptoms of affective distress after adjustment for age, pain duration, and compensation status. Similarly, comparisons between patients who had experienced a potentially traumatic onset of pain with those who had experienced a non-traumatic or spontaneous or insidious onset of pain also revealed no significant differences on the aforementioned variables. In contrast, compensation status, age, and a number of cognitive variables were significant predictors of pain severity, pain-related disability, and depression. The final study investigated the impact of type of pain onset and posttraumatic stress symptoms on response to a multidisciplinary cognitive-behavioural pain management program. Unlike the previous study, this treatment outcome study revealed a number of differences between onset groups. Most notably, patients who had experienced an insidious or spontaneous onset of pain reported greater improvements in pain severity and maintained these improvements more effectively over a one month period than patients who had experienced pain in the context of an accident or other specific incident. There was also limited evidence that improvements in depression favoured patients who had experienced an insidious or spontaneous and non-traumatic onset of pain. Consistent with this, posttraumatic stress symptoms were a significant predictor of treatment outcome, with higher levels of symptoms being associated with smaller improvements in pain-related disability and distress. Notably, this study also revealed that certain cognitive variables (i.e. catastrophising, self-efficacy, and fear-avoidance beliefs) were also significant predictors of treatment outcome, consistent with previous findings in the pain literature. This provided some perspective on the relative roles of both PTSD symptoms and cognitive variables in adjustment to persisting pain and treatment response. These findings were all consistent with expectations and with previous research. Implications for future research and for the assessment and treatment of chronic pain patients who present with posttraumatic stress symptoms are discussed.

Doctor of Philosophy / Despite the demonstrated efficacy of cognitive-behavioural therapy for chronic pain, recent research has attempted to identify predictors of treatment outcome in order to improve the effectiveness of such treatments. This research has indicated that variables such as the nature of the onset of the pain and psychopathology are associated with poor adjustment to chronic pain. Accordingly, these variables might also be predictive of poor response to treatment. Individuals who experience a sudden onset of pain following an injury or accident, particularly when the instigating event is experienced as psychologically traumatic, may present for treatment with high levels of distress, including symptoms consistent with a posttraumatic stress response. The impact of this type of onset of pain and posttraumatic stress symptoms on adjustment to chronic pain and treatment outcome is the focus of this thesis. Three studies were conducted to clarify and extend earlier research findings in this area. Using 536 patients referred for treatment in a tertiary referral pain management centre, the first study examined the psychometric properties of a widely used self-report measure of posttraumatic stress symptoms (the PTSD Checklist, or PCL), modified for use in a chronic pain sample. This study provided preliminary support for the suitability of the PCL as a self-report measure of Posttraumatic Stress Disorder (PTSD) symptoms in chronic pain patients. However, the study also highlighted a number of issues with the use of self-report measures of posttraumatic stress symptoms in chronic pain patient samples. In particular, PCL items enquiring about symptoms which are a common aspect of the chronic pain experience (e.g. irritability, sleep problems) appeared to contribute to high mean scores on the PCL Avoidance and Arousal subscales. Furthermore, application of diagnostic cut-off scores and an algorithm recommended for the PCL in other trauma groups suggested that a much larger proportion of the sample was identified as potentially meeting diagnostic criteria for PTSD than would have been expected from previous research. The second study utilised the modified PCL to investigate the impact of different types of onset of pain (e.g. traumatic onset) and posttraumatic stress symptoms on adjustment to chronic pain in a sample of 196 chronic pain patients referred to the same centre. For patients who experienced the onset of pain related to a specific event, two independent experts in the field of PTSD determined whether these events satisfied the definition of a traumatic event according to DSM-IV diagnostic criteria. Adjustment was assessed through a number of validated measures of mood, disability, pain experience, and pain-related cognitions. Contrary to expectations, comparisons between patients who had experienced different types of onset of pain revealed few significant differences between them. That is, analyses comparing patients presenting with accident-related pain, or pain related to other specific events, to patients who had experienced spontaneous or insidious onset of pain revealed no significant differences between the groups on measures of pain severity, pain-related disability, and symptoms of affective distress after adjustment for age, pain duration, and compensation status. Similarly, comparisons between patients who had experienced a potentially traumatic onset of pain with those who had experienced a non-traumatic or spontaneous or insidious onset of pain also revealed no significant differences on the aforementioned variables. In contrast, compensation status, age, and a number of cognitive variables were significant predictors of pain severity, pain-related disability, and depression. The final study investigated the impact of type of pain onset and posttraumatic stress symptoms on response to a multidisciplinary cognitive-behavioural pain management program. Unlike the previous study, this treatment outcome study revealed a number of differences between onset groups. Most notably, patients who had experienced an insidious or spontaneous onset of pain reported greater improvements in pain severity and maintained these improvements more effectively over a one month period than patients who had experienced pain in the context of an accident or other specific incident. There was also limited evidence that improvements in depression favoured patients who had experienced an insidious or spontaneous and non-traumatic onset of pain. Consistent with this, posttraumatic stress symptoms were a significant predictor of treatment outcome, with higher levels of symptoms being associated with smaller improvements in pain-related disability and distress. Notably, this study also revealed that certain cognitive variables (i.e. catastrophising, self-efficacy, and fear-avoidance beliefs) were also significant predictors of treatment outcome, consistent with previous findings in the pain literature. This provided some perspective on the relative roles of both PTSD symptoms and cognitive variables in adjustment to persisting pain and treatment response. These findings were all consistent with expectations and with previous research. Implications for future research and for the assessment and treatment of chronic pain patients who present with posttraumatic stress symptoms are discussed.

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Psychological adjustment to chronic pain has been recently explored within three separate frameworks: a behaviour-focused account of chronic pain acceptance within the broader remit of Acceptance and Commitment Therapy; an emotion-focused approach with various research programs investigating the role of anger, fear, depression and also shame and positive emotions in chronic pain; and a cognitionfocused perspective more recently reframed in terms of illness perceptions as part of a wider model of response to health threats, the Self-Regulatory Model. Although these frameworks have broad areas of overlap, limited research has been directed at integrating acceptance, emotions and illness perceptions into a common, comprehensive account of psychological adjustment to chronic pain. Such an account would be beneficial both for providing a parsimonious approach that would guide further research and for developing pain management interventions that would take advantage of existing research from all three domains. The aim of the present thesis was to explore the possibility of integrating these separate areas by studying the relationships between the main concepts (acceptance, emotions, and illness perceptions) in the context of chronic pain. Based on a review of the relevant conceptual and methodological issues of each domain, a theoretical analysis of the similarities and differences between them was developed, with particular emphasis on the potential of existing models to support an integrative account. This analysis provided specific hypotheses regarding each domain and the interrelationships between them, which were investigated in a longitudinal study on a heterogeneous sample of 265 chronic pain patients using the services of the NHS Lothian Pain Clinic and several patient support organisations. Data were collected via postal and online questionnaires at 3 time points, at 41/2-month intervals (21% attrition rate). Validated questionnaires were used to measure the relevant constructs, with additional questions obtaining information regarding health status, medical history and demographics. The confirmatory analysis (employing a variety of statistical procedures, from correlation to multiple regression, factor analysis, cluster analysis and structural equation modeling) largely confirmed the expected relations within and between domains and was also informative regarding the most suitable data reduction methods. A detailed psychometric analysis of the questionnaires used offered a complementary view on the theoretical and methodological issues involved. An additional exploratory analysis focused on identifying the comparative characteristics of acceptance, emotions, and illness perceptions in predicting health status indicators, controlling for contextual factors such as medical history and demographics. Although no significant longitudinal changes were identified in most parameters (confirming the clinical observation of chronic pain as a stable condition), the longitudinal data allowed an analysis of the stability of the concepts and of the magnitude of their relationships in this patient sample. The analysis of intra- and interpersonal variation via hierarchical longitudinal modeling confirmed the stability of the data, highlighted the necessity of studying variation at both levels, and revealed interesting moderation effects, explained via the proposed concept of ‘discrimination ability’ and several alternative mechanisms. These results can be considered as first steps towards an integrative model of psychological adjustment to chronic pain. It is proposed that the behavioural, cognitive and emotional aspects need further conceptual clarification and these future efforts can be supported by the Cognitive-Affective Model of the Interruptive Function of Pain, within the wider framework of the Self-Regulatory Model.

Introduction/Background: Chronic widespread pain (CWP) affects around 11% of the population and while aetiology is well documented it has been difficult to translate this into effective management strategies. Patients in clinical trials are known to be different from the patient populations that they represent and treatment preference is one area where they may differ. Treatment preference may also influence outcome, particularly when participants cannot be blinded to treatment allocation. Aims: To assess whether patient treatment preference has an influence on 1. Recruitment, 2. Outcome, and 3. Adherence In a clinical trial of interventions for CWP. Methods: In the MUSICIAN trial, a 2x2 factorial trial of exercise and telephone cognitive behavioural therapy (T-CBT) for CWP, treatment preferences were recorded when eligibility was assessed using a population postal survey. Eligible individuals who did and did not go on to enter the trial were compared to address aim 1. Trial participants were followed up after 6 months of treatment and outcomes were compared according to whether they received their preferred treatment to address aim 2 and T-CBT and exercise logs were used to assess adherence to examine aim 3. Results: Eligible individuals were more likely to be randomised into the MUSICIAN trial if they expressed a treatment preference in the screening questionnaire (Relative Risk 1.46, 95% confidence interval 1.19-1.79). Treatment preferences were also associated with prognostic factors (anxiety and fear of movement). At follow-up participants were more likely to achieve a good outcome (global assessment of change) if they had received their preferred treatment (Relative Risk 2.50, 95% confidence interval 1.54-4.03)and this may be due to those individuals being more likely to adhere to treatment programmes. Conclusions: Wherever possible participant treatment preferences should be recorded prior to randomisation in clinical trials. Additional benefit may be gained in clinical practice by tailoring treatment to patients’ preferences.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfillment of the requirements for the degree of Master of Science in Medicine in the branch of Anaesthesiology Johannesburg, 2014 / BACKGROUND: Chronic pain is a biopsychosocial phenomenon that can have a profound impact on people’s lives. Internationally, chronic pain is being recognised as a health priority. South Africa is a developing country with limited resources that are directed at catering for a growing population where life threatening conditions like Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS), violent crimes, and poverty predominate. Auditing the Helen Joseph Hospital Pain Management Unit (HJHPMU) is a step towards addressing the paucity of epidemiological data on chronic pain in South Africa. Clinical records are a basic clinical tool that also serves as a medicolegal document. It is essential that these records are legible and complete. AIM: The aim of this study was to describe the profile of chronic pain patients at the HJHPMU for 2011 and to determine the adequacy of record keeping. METHODOLOGY: A retrospective, contextual, descriptive study design was utilised. A consecutive sampling method was used and the study sample included the HJHPMU database and all files of adult patients that attended the HJHPMU during the period January 2011 to December 2011. Patient files were excluded from the audit if insufficient data were found. Descriptive statistics were used to analyse the data obtained during the study. Frequencies and percentages have been reported. A Chi-­‐squared test was utilised to analyse any association between gender and type of pain. RESULTS: There were 475 patients in the HJHPMU database for the year 2011 and 190 of these patients were excluded from the study due to illegible handwriting, duplication in the HJHPMU database, missing data such as no hospital number recorded, no initials to a surname, or the file not found. This resulted in a study sample of 285 patients. The HJHPMU had 215 (75,44%) pre-­‐existing patients and 70 (24,56%) new patients during the year 2011. The preponderance of patients were in the 41-­‐60 year age group, with 146 (51,23%) patients presenting in this age group. Of the 285 patients in the study, 91 (31,93%) patients were male and 194 (68,07%) were female. The most common complaint was of lower back pain (LBP). There were 97 (34,04%) patients with a diagnosis of spinal pain and 59 (20,70%) with Failed Back Surgery Syndrome (FBSS). There were 164 patients with a relevant surgical history. This included 46 (28,05%) patients that had been involved in a traumatic event, 47 (16,49%) patients that had surgery other than spinal surgery that was relevant to their pain diagnosis, and 71 patients (43,29%) that 4 had spinal surgery that was relevant to their diagnosis. A Chi-­‐squared test was performed on the relationship between gender and the type of pain, and a p value of 0.001 was found. When relating the type of pain with age, mixed pain and nociceptive pain was found to be most common in those aged >60 years (n=26), whereas neuropathic pain was found to be most common in the 41-­‐60 year age group (n=43). CONCLUSION: With the limited data from this study, the profile of patients with chronic pain in South Africa seems to not differ grossly from data collected internationally. The most pertinent finding of this study is the inadequacy of record keeping.

Class of 2007 Abstract / Objectives: To conduct a survey instrument on a pharmacists’ knowledge of and attitudes toward dispensing narcotic medications for the management of chronic pain. Methods: A focus group of 39 pharmacy managers for a local chain drug store reviewed 6 knowledge questions and 10 attitude statements for content validity, clarity and readability. The results of their responses to the survey and other comments were tabulated and analyzed. Results: The focus group sample was small and results were not statistically significant. Pharmacists were highly confident about their training, yet most did not score well on the test, especially those questions designed to distinguish between addiction, pseudo-addiction and tolerance. This limited knowledge may have been related to age since many of the wrong answers selected were based on older definitions. Several questions and statements were identified as ambiguous, plus having unclear directions or incorrect information. Focus group discussions confirmed the limited knowledge found in the survey and clarified pharmacist's responses to the attitude statements. Conclusions: What is clear from the literature and our study is that pharmacists' knowledge about chronic pain and the uses of opioids strongly influences their attitdues. Therefore, the survey questions and statements need to be reworded and restructured to specifically evaluate the relationship between pharmacists' knowledge and their attitudes.

BACKGROUND: The biopsychosocial model of pain suggests that one’s perception of pain is affected by one’s beliefs about pain (Moseley & Butler, 2015). Metaphors have been shown to be effective in educating the patient about pain, which in turn reduces it (Gallagher et al., 2013). How might metaphors be used by the patient to express their pain, and what do these metaphors have in common? This qualitative study will examine the pain-expressing metaphors (PEMs) used by the pediatric chronic pain patients in a graded exposure treatment. METHODS: 36 patients recruited from Pain Treatment Service at Boston Children’s Hospital and the Pediatric Headache Program were enrolled GET Living, a pediatric chronic pain intervention composed of a series of individualized graded exposure sessions. Of these 36 patients, video recordings for GET Living sessions were available for 19. Of these 19 patients, video recordings of at least 5 sessions were available for 11 patients. Each video-recorded session for these 11 patients was viewed, reviewed, and coded for the use of PEM by the patient. RESULTS: Each of the PEMs patients used in this study could be organized into one of 6 categories: Sharp, Burning, Throbbing, Spectrum, Physical Qualities, and Other Sensation. “Other Sensation” was the category into which the most individual PEMs fell, but the category that had PEMs used by the most number of patients was “Sharp.” CONCLUSION: This study added to existing literature regarding categories of pain metaphors, supporting groupings such as sharp, throbbing, and burning. This study furthermore described groupings such as characterizing pain as a spectrum and characterizing pain as something with physical qualities. Future studies with more robust data sets could code PEMs in the same way and then conduct a quantitative analysis of metaphor use by patients enrolled in GET Living, correlating metaphor use with measures such as fear of pain and functional disability as recorded in the GET Living Child Assessment. / 2018-07-11T00:00:00Z

The adverse interaction between smoking and chronic pain has been known for decades. A variety of chronic pain conditions – ranging from headache to low back pain to fibromyalgia – markedly exacerbate smoking prevalence and intensity in packs per day among multiple patient populations. In patients seeking pain treatment, the prevalence of smoking approaches 50%, compared to less than 20% in the general population. Perhaps not surprisingly, the relationship is bidirectional: not only does persistent pain increase rates and intensity of smoking, but smoking also appears to exacerbate both the intensity and associated impairment of chronic pain. In fact, smoking appears to place individuals at risk for developing a chronic pain condition and may also facilitate the transition from acute to chronic pain. The growing body of literature documenting these associations has led to the proposition of a positive feedback loop: individuals smoke in part to cope with their pain, but smoking actually worsens the pain. Despite the strong evidence for the existence of this adverse interaction, the mechanisms responsible for it remain poorly understood. A number of preclinical and clinical studies have documented that nicotinic acetylcholine receptor (nAChR) agonists, e.g., nicotine, have analgesic efficacy in the acute pain setting, such as that produced experimentally in the research laboratory or experienced by patients postoperatively. In contrast, the role of nAChR activation in modulating chronic pain is less well characterized. The experiments described in this thesis determine whether persistent pain diminishes the antinociceptive (analgesic) efficacy of an α4β2 nAChR agonist in the rostral ventromedial medulla (RVM), a key brainstem pain modulatory nucleus, and subsequently begin to elucidate the mechanisms by which persistent pain elicits this plasticity. The complete Freund’s adjuvant (CFA) model of chronic pain was employed to test the hypothesis that persistent inflammatory injury diminishes the antinociceptive efficacy of the selective and potent α4β2 nAChR agonist epibatidine in key brainstem pain modulatory nuclei. Paw withdrawal latency to a noxious heat stimulus was used to evaluate the anti-hyperalgesic and antinociceptive effects of epibatidine microinjected in the RVM or periaqueductal gray (PAG) of male rats. The effects of epibatidine were assessed both in uninjured animals and in animals at different times after intraplantar CFA injection. Interestingly, pretreatment with an α4β2-selective antagonist demonstrated that the antinociceptive effects of epibatidine in naïve rats were mediated by α4β2 nAChRs in the RVM but not in the PAG. While the antinociceptive effects of epibatidine in the RVM were abolished after two weeks of inflammatory pain, the anti-hyperalgesic effects remained unchanged. Surprisingly, epibatidine no longer appeared to be acting primarily at α4β2 nAChRs as early as four hours after injury. Persistent inflammation did not alter the anti-hyperalgesic or antinociceptive effects of epibatidine in the PAG. Radioligand binding studies were conducted to test the most parsimonious hypothesis that a global reduction in α4β2 nAChR number or binding affinity during persistent injury was in part responsible for the decreased efficacy of epibatidine in the RVM after intraplantar CFA. Saturation binding using [3H]-epibatidine in membrane homogenates prepared from RVM and PAG tissue revealed no differences in receptors between saline- and CFA-treated rats at any time after injury, suggesting that a whole-nucleus reduction in nAChRs could not explain the observed behavioral phenomena. To query functional changes with greater resolution, whole-cell patch clamp electrophysiology was employed to begin assessing the consequences of nAChR activation by nicotine at the level of the neuron. Initial studies performed in the locus coeruleus demonstrated that all neurons responded to nicotine with an inward current that desensitized with continued exposure to the drug. Neurons in the RVM exhibited significantly more heterogeneity in their response to nicotine: desensitizing inward currents were seen in some; sustained outward currents in others; inward currents followed by outward currents in a third population; and still others had no response to nicotine exposure. The sustained outward currents persisted in the presence of the sodium channel blocker tetrodotoxin, were not blocked by an α4β2 nAChR-selective antagonist, and appeared to be mediated by G protein-coupled receptors and potassium channels. Taken together, the present results demonstrate that persistent inflammatory injury produces adaptive changes in nicotinic signaling in the RVM such that the antinociceptive effects of epibatidine activation are abolished in a time-dependent manner. These changes cannot be attributed to a whole-nucleus reduction in α4β2 nAChRs. However, nicotinic signaling in the RVM is complex, and small alterations in the pre- or postsynaptic actions of nicotine may have significant ramifications for the overall nociceptive sensitivity of an animal. The data presented here suggest that plasticity in nicotinic signaling within the bulbospinal pain modulatory pathways may in part explain the adverse interaction between smoking and chronic pain observed in humans.