Endothelin-1 (ET-1), a 21-amino acid peptide, exerts multiple functions including vasoconstriction, neurotransmission and neuromodulation. The correlation between ET-1 and pain was examined by localized injection into the animal showing that pain response was induced in the peripheral nervous system, but reduced in the central nervous system. In addition, the pathogenic effect of ET-1 in the nervous system was found to be cell-type specific as ET-1 expression was significantly induced in the astrocytes under certain pathological conditions such as stroke and Alzheimer’s disease. Therefore, in this study, it aims to determine the role of astrocytic ET-1 in inflammatory pain. To better illustrate such notion, transgenic mouse line over-expressing ET-1 in the astrocytes (GET-1) was generated. Under physiological conditions in GET-1 mice, it was revealed that its gross anatomy, in addition with thermal heat and mechanical pain-thresholds, were indistinguishable between GET-1 and its age-matched non-transgenic control (NTg). Inflammatory pain was then induced in the GET-1 mice and NTg mice by subcutaneous formalin injection. Spontaneous and heat-induced pain response were evaluated and analyzed based on the two phases of pain response (i.e. acute and tonic responses). Our results indicated that GET-1 mice exhibited less inflammatory pain-like response when compared to the NTg control, implicating that astrocytic ET-1 over-expression modulates inflammatory pain response. The molecular mechanism substantiating the reduction in this response may be due to the basal expression of pain-mediators in GET-1 mice. Further results showed that over-expression in astrocytic ET-1 evoke an up-regulation in calcitonin gene-related peptide (CGRP) as well as the glutamate transporter-1 (GLT-1), also known as excitatory amino-acid transporters (EAAT2). In addition, under formalin-induced pathological pain, over-expression in astrocytic ET-1 was found to negatively regulate GLT-1 transcription. These findings elucidate the extent that ET-1 contributes to the inflammatory pain pathway via ET-1 and GLT-1 interactions. Overall, this study not only pointed out the involvement of astrocytic ET-1 in inflammatory pain processing, but it also warrants further investigation into the molecular mechanism and potential therapeutic intervention of ET-1-mediated pain. / published_or_final_version / Anaesthesiology / Master / Master of Philosophy

According to the World Health Organization, life-threatening infectious diseases, even in remote and vulnerable locations, can be minimised through immunisation. Vaccines interact with the immune system to produce an immune response similar to that produced by natural infection. However, about 10% of the population avoid vaccination and other needle procedures because of “needle fear”. Because of the prevalence of injection pain and more concern about the adequacy of pain management, and with the steadily increasing number of recommended childhood immunisation, we identified a need for evidence-based guidelines on pain management to be developed in our local setting through translational nursing practice. After a critical appraisal of randomised controlled trials and systematic reviews, it is highly recommended that “topical anaesthetics are effective in reducing vaccination pain” (Grade A recommendation, based on level I evidence by SIGN). In order to facilitate practice from evidence, the implementation potential, transferability, feasibility and cost-benefit ratio - has been examined, and an evidence-based guideline has been developed simultaneously for the new practice. With the identification of stakeholders and the development of a communication plan, potential users of the guideline and pilot testing are discussed. Innovation outcomes and their effectiveness are examined and explored. It is expected that, through this translational nursing practice, vaccination induced pain and distress among healthy children can be managed well, according to the best evidence and up-to-date recommendations. / published_or_final_version / Nursing Studies / Master / Master of Nursing

Objective: Chronic back pain is highly prevalent in orthopaedic clinics. The aim of the study was to investigate the relationship of psychological factors affecting disability and distress outcomes in chronic low back pain patients. Clinicians shared the impression that chronic pain patients resulted from Injury on Duty (IOD) were particularly difficult to manage. Profiles of IOD patients and non-IOD patients were compared. Methods: The present study is a prospective follow-up study. Fifty-four patients from a public orthopaedic out-patient clinic were assessed with low back pain as their primary complaint. Self-report inventories together with semi-structured interview were used to assess patients’ pain intensity, pain disability, psychological distress, positive and negative affect, as well as relevant pain-related parameters including pain catastrophizing thought, pain-related fear, pain self-efficacy and chronic pain acceptance. Patients were interviewed during their first visit to the orthopaedic out-patient clinic (i.e. Time 1), after 6 months (i.e. Time 2) and after 1 year (i.e. Time 3) of the first consultation. Both qualitative and quantitative analyses were conducted. Results: Chronic pain acceptance predicted mid-term and long-term pain disability and psychological distress at a period of one year after their initial assessment. However, the pain-related parameters of pain catastrophizing, pain-related fear and pain self-efficacy did not show a significant predictive effect on outcomes. Pain rating is an inadequate estimate to assess patients’ level of disability and psychological status. The meaning of pain is important for patients to make sense of their pain experience and employ appropriate coping strategies. Attaching a positive value to pain helps patients to accept their pain. In addition, half of the chronic pain patients showed a need for psychiatric services at one year follow-up, pointing to a high co-morbidity between chronic pain and psychiatric problems. Among the 54 patients, 17 (31.5%) were injured on duty (IOD). More IOD patients than non-IOD patients took sick leaves or were not working during the year. However, there is no significant difference between IOD group and non-IOD group on psychological distress, pain disability and other pain-related measures across 3 time points. Discussion and Conclusion: Pain problems in the context of chronic pain are different from those in the context of acute pain. Intervention focusing on pain relief is inadequate to treat patients’ chronic pain. A multi-factorial perspective is needed to understand and develop suitable models to account for chronic pain experience instead of just relying on the prevalent fear-avoidance model. A more comprehensive assessment that is tailored to patients’ needs is necessary for more effective rehabilitation. Chronic pain patients’ need for psychiatric intervention is also highlighted, with a focus on work-related issues for IOD patients. / published_or_final_version / Psychiatry / Doctoral / Doctor of Philosophy

Dissociative symptoms and abnormalities in pain perception have been associated with a range of disorders. We tested whether experimentally induced increases in state dissociation would cause an analgesic response, and whether this effect would be moderated by participants' history of trauma and dissociative experiences. Participants (n=120) were classified based on their histories of traumatic and dissociative experiences: No trauma or dissociation (NN), trauma without dissociation (TN), or trauma with dissociation (TD). All participants were randomized to a dissociation induction condition via audiophotic stimulation or a credible control condition and were compared on prepost changes in subjective pain and pain tolerance in response to a standard cold-pressor test. Unexpectedly, dissociation induction did not lead to greater pain tolerance or reduced self-reported pain. However, increases in state dissociation significantly predicted increased immersion time and decreased subjective pain. / text

The purpose of this study was to elucidate relationships among habitual physical activity level, endogenous opioid level, postoperative opioid analgesic, and experiences of acute pain in response to the noxious stimulation of a subsequent orthopedic surgical procedure. Specifically, the study examined (1) the relationship between habitual activity and preoperative level of endogenous opioids in peripheral blood, and (2) whether habitual activity predicts perception of pain intensity or distress in response to a subsequent noxious stimulus. The study utilized a descriptive correlational design with causal modeling methodology to assess a five-stage theory. The convenience sample was comprised of 36 English-speaking adult subjects hospitalized for orthopedic surgeries. The theoretical concepts, acute pain intensity and distress, were indexed three times for each subject by visual analogue scales. Reliability and validity of the scales were assessed by correlation with concurrent pain measurements using randomized verbal descriptor lists. Multiple regression statistical techniques were used to estimate the theory; violations of causal modeling and statistical assumptions were assessed by residual analysis. For this sample, the strongest predictors of postoperative pain were the immediately preceding comparable indices of pain intensity or pain distress. Approximately 31% of the variance on postoperative analgesic was predicted by the combined effects of immediate postoperative pain and habitual activity. Although activity was not significantly related to endogenous opioid level in peripheral plasma, activity directly and positively influenced immediate postoperative pain intensity (Beta = .37), 24-hour pain distress (B = .27), and total opioid analgesic received in the initial 24 postoperative hours (Intensity B = .40; Distress B = .50). Endogenous opioid was significantly related only to immediate postoperative pain distress (B = -.26). More physically active patients reported greater immediate postoperative pain intensity and greater 24-hour pain distress; they received more postoperative exogenous analgesic. Incorporation of information about activity as a potential determinant of operative pain experiences would increase validity of nursing assessments on which pain interventions are based. Patients in acute pain would benefit from this improved scientific basis for pain assessment.

The purpose of the study was to investigate the structure of coping with chronic pain and to develop a standardised, reliable and valid ~t to measure coping with chronic pain. The use of this instrument as a measure of change in the evaluation of a local Pain Management Programe was investigated. The Pain Coping Questionnaire was developed from analysis of responses of 298 chronic pain patients to a self-report questionnaire concerned with coping with chronic pain. Following empirical psychometric investigations of reliability and validity, four psychologically meaningful dimensions were identified. One dimension, the General Coping Measure, was a measure of psycho-social adjustment to chronic pain. Three dimensions measured beliefs in the use of cognitive and behavioural pain coping strategies. One dimension, Active Coping Strategies, measured active pain coping strategies. Two dimensions, Avoidance and Use of Drugs, measured passive pain coping strategies. Belief in the use of active pain coping strategies was predictive of good psycho-social adjustment. Belief in the use of passive pain coping strategies was predictive of poor psycho-social adjustment. The results from outco~e studies indicated that the Pain Coping Questionnaire was a sensitive measure of change. The Pain Manag~.ment Programne had beneficial effects with respect to short-term outcome. Limitations were discussed. It was concluded that the Pain Coping Questionnaire represents an original contribution that is likely to have broad applications in the assessment and treatment of chronic pain patients.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Study Design. Retrospective analysis. Objective. To determine if the use of adjunctive pain medications (subcutaneous bupivacaine, dexmedetomidine infusion, and intravenous ketorolac) will reduce the need for opioids, reduce postoperative pain, and shorten length of hospital stay in patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion. Methods. Retrospective review of children 10 to 18 years with adolescent idiopathic scoliosis receiving posterior spinal fusion surgery over the past 10 years at Phoenix Children’s Hospital. Physicians managed the patients’ pain postoperatively with adjunctive medications in addition to intravenous and oral opioids. Variables of interest were local anesthetic bupivacaine delivered subcutaneously via elastomeric pain pump, sedative/analgesic dexmedetomidine infused for up to 24 hours postoperatively, and the NSAID ketorolac delivered intravenously. These three medications were used either alone or in some combination determined by the physician’s clinical judgment. Primary outcomes analyzed were normalized opioid requirement after surgery, VAS pain scores, and length of stay in the hospital. Results. One hundred and ninety-six children were analyzed with no significant differences in demographics. Univariate analysis showed that all three adjunct medications improved outcomes. A multivariate regression model of the outcomes with respect to the three medication variables of interest was developed to analyze the effects of the three medications simultaneously. The regression analysis showed that subcutaneous bupivacaine significantly reduced normalized opioid requirement by 0.98 mg/kg (P = 0.001) and reduced VAS pain scores by 0.67 points (P = 0.004). Dexmedetomidine significantly reduced the average VAS pain scores in the first 24 hours by 0.62 points (P = 0.005). Ketorolac had no effect in the multiple regression analysis. Conclusion. The use of subcutaneous bupivacaine provides good analgesia with low pain scores. A reduction in opioid requirement is beneficial and may be directly related to presence of the bupivacaine pump, although this may be limited by potential treatment bias. The three adjunct medications improve our outcomes favorably and should be studied prospectively.

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