Tesi sul tema "Pain in animals Treatment"

"April 2002" Bibliography: leaves 190-202. Examines the suitability of the [alpha] 2 adrenoreceptor agonist xylazine for providing safe and effective analgesia in 2 settings: for post-surgical pain in adult sheep used for biomedical research, and for routine husbandry procedures applied to lambs on farms, such as mulesing, tail-docking and castration. Concludes in setting 1 that intramuscular administration of xylazine was simple to perform yet was characterized by a rapid peak analgesic effect with a reasonable duration of action and minimal deleterious effects on cardiac output, blood pressure or arterial blood gases. In setting 2 the anti-nociceptive effects in lambs are of a similar magnitude and duration to those in adult sheep when the dose was scaled for body weight. A ranking of the relative painfulness of husbandry procedures was developed and used to assess the efficacy of intramuscular xylazine.

Dissertação de Mestrado Integrado em Medicina Veterinária
ABSTRACT - Hoof lesions in dairy cattle have a great impact, either in production as in animal welfare. Trimming may cause severe pain resulting in violent reaction with risk for humans’ safety as well as affecting the animal’s immediate welfare. These interventions are usually carried out by non-veterinarian technicians, without any kind of pain management training. An efficient pain management is not only an ethical obligation, as also allows a better manipulation and meticulous treatment. The present study had the main purpose to test the efficiency of Tri-Solfen®, with a combination of local anaesthetics – lidocaine and bupivacaine - adrenaline and cetrimide in a topical gel form. The efficiency of this formulation has already been tested in other procedures, such as mulesing, castration, disbudding and tail docking in lambs and calves, significantly reducing pain related behaviours. Being dairy cows a second objective was to assess lidocaine, bupivacaine and metabolites, as well as cetrimide residues in milk to determine the safety of use in milking animals. The selected cows were in the drying off period and lameness scoring was performed when entering the chute. Before trimming, each animal was randomly distributed to two groups: C – usual trimming with no pain control; T – trimming with local anaesthetics being applied once live corium was exposed. Lesions’ characteristics were registered. Algometry measurements were performed before and after intervention, to assess animal reaction to pressure. During corrective trimming, behaviour observation was done by two persons blind to treatment. Lameness scoring was again performed at the end of the intervention. Non-parametric tests and analysis of variance were performed. Analysis of data showed that treatment significantly influenced reaction to trimming and lameness score after trimming on the treated group, when compared with the not treated group. Algometry values showed increased pressure threshold after application of Tri-Solfen. Anaesthetics residues are below the LOQ value in all animals after the first milking, except in one sample at the fourth milking. This study suggests that the use of topical local anaesthetics with lidocaine and bupivacaine helps reducing pain inflicted during corrective trimming of severe lesions, enhancing animal welfare and providing trimmer safety due to diminishing pain related behaviours. We also demonstrated that the levels of anaesthetics and/or metabolites residues are very low in all animals in the four milkings after treatment.
RESUMO - Uso de Tri-Solfen no Controlo da Dor Durante o Tratamento de Lesões Podais em Bovinos de Leite - As afeções podais em vacas leiteiras têm um enorme impacto quer sobre a produção, quer sobre o bem-estar animal. O desbridamento das lesões pode causar dor intensa, levando a reações do animal que dificultam o maneio e a segurança do mesmo e do operador. Por norma, estas intervenções são realizadas por técnicos não médicos veterinários sem formação no controlo da dor. O maneio eficaz da dor não só é uma obrigação ética, como permite uma mais fácil manipulação e um tratamento mais minucioso. O presente estudo teve como principal objetivo avaliar testar a eficácia de um medicamento, Tri-Solfen®, que tem na sua composição uma associação de anestésicos locais – lidocaína, bupivacaína – adrenalina e cetrimida, na forma de gel tópico. A eficácia desta formulação já foi avaliada noutros procedimentos, como mulesing, castração, descorna e amputação de cauda em borregos e novilhos, tendo reduzido significativamente os comportamentos de dor. Sendo animais leiteiros, um secundo objetivo foi detetar a presença de lidocaína, bupivacaína e cetrimida, em amostras de leite após aplicação do produto. As vacas selecionadas encontravam-se no período de secagem e foram classificadas quanto ao grau de claudicação quando conduzidas ao tronco. Antes do início da aparagem cada vaca foi aleatoriamente alocada a um de dois grupos: C – aparagem sem aplicação do medicamento; TriS – aparagem com aplicação do anestésico tópico sobre a lesão do córion. As características das lesões encontradas foram registadas. Foram efetuados testes de algometria antes e após a intervenção, para avaliar a reação do animal a diferentes graus de pressão. Durante a aparagem curativa, dois observadores cegos ao tratamento avaliaram os comportamentos de dor. O grau de claudicação foi novamente avaliada no fim da intervenção. Na análise estatística dos dados foram aplicados testes não paramétricos e análise de variância. A análise dos dados demonstra existir uma redução da reação à aparagem e do grau de claudicação à saída do tronco, no grupo tratado comparativamente com o grupo não tratado. Os valores de algometria demonstram maior resistência à pressão após aplicação do medicamento. Resíduos anestésicos encontraram-se abaixo do LOQ em todos os animais após a primeira ordenha, exceto numa amostra da quarta ordenha. O estudo parece sugerir que a utilização da combinação de anestésicos locais tópicos reduz a dor durante a aparagem curativa, melhorando o bem-estar animal e aumentando a segurança do operador por redução dos comportamentos associados à dor. Os valores de resíduos anestésicos e/ou metabolitos foram consideravelmente baixos em todos os animais nas quatro ordenhas após aplicação.
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Within the livestock sector, farmers and veterinarians are two groups of people who play a pivotal role in maintaining the health and welfare of animals. How the different welfare needs of farm animals are perceived and prioritised by these two caretaker groups will have direct implications for the animals in their care. People’s perceptions and attitudes directly influence their behaviour, and research has demonstrated that positive attitudes towards animals are paramount to ensuring good animal welfare. The prevention and mitigation of pain is an important component to ensuring good animal welfare, as pain has the potential to negatively affect both physical and mental health. How pain in animals is perceived by farmers and vets will influence how it is managed. Therefore, understanding how farmers and vets: view the capacity of animals to experience pain, perceive the pain severity associated with different conditions and procedures, view the importance of pain mitigation in relation to other welfare needs, and deem the necessity of analgesic use in livestock, is vital. Four separate questionnaire based studies were conducted to assess these attitudes in farmers and veterinarians as well as in agriculture and veterinary students, as these students will be the next generation of farmers and veterinarians. Overall, farmers and vets were found to have positive attitudes towards pain in livestock. Although the capacity of cattle and sheep to feel pain was perceived to be lower than that of humans it was still rated highly. In addition, positive beliefs about the benefits of pain alleviation, the negative impacts of pain on production and welfare, and the importance of prompt treatment and pain management for good welfare were held. Cattle farmers had more positive attitudes towards pain and analgesic use than sheep farmers. This difference was most evident around areas of resource availability, such as time and labour, and the practicalities associated with pain identification and drug provision. Farmers, vets and students perceived lameness to be a painful condition, with the perceived severity of pain being closely related to the perceived severity of the disease. In addition, participants reported a greater emotional reaction in instances where they rated lameness and pain more highly. Furthermore, a positive relationship was found between lameness, pain and emotional reaction scores and the decision to catch a lame sheep for inspection. The majority of students had positive views towards pain in farm animals, believing that: farm animals were capable of experiencing pain, prompt treatment and the provision of pain relief were the two most important elements of welfare, and that farm animals benefit from pain alleviation. However, there was a perceived difference between a number of animal species in their capacity to feel pain, with livestock species being viewed as having a lesser capacity than companion animals and humans. In addition effects of gender were found, with females reporting higher levels of empathy and compassion towards lame sheep, and rating pain higher. Furthermore, female students had a stronger belief that animals were sentient beings than did males. These four studies found that views on pain and analgesic use in livestock were generally positive. However, differences between individuals and between groups were found in a number of areas including how observers perceived the severity of painful conditions and procedures and in the capacity of different animal species to experience pain. These differences in attitudes may affect the decisions farmers and vets make regarding the treatment of pain, which is likely to have implications for farm animal welfare.

The purpose of the current study was to investigate the effects of a multidisciplinary pain management program on five measures of subjective psychosocial factors. Ninety-five participants in the comprehensive multidisciplinary treatment group and the standard medical intervention control group were surveyed about various psychosocial factors using Axis II of the West Haven - Yale Multidimensional Pain Inventory (MPI), pre- to post-treatment. It was hypothesized that post-treatment levels would be significantly lower than pre-treatment levels for all five psychosocial variables. Additionally, gender and ethnicity variables were examined. Based on preliminary analyses indicating pre-treatment differences between the experimental and control group, five 2 x 2 x 3 analyses of covariances (ANCOVAs) were used to examine the above hypotheses. Results indicated significant differences between the treatment conditions on measures of control, with the comprehensive group feeling more in control than the standard group at post-treatment. No other significant main effects for treatment condition were found on the measures of pain severity, interference with daily activities, negative mood, or social support. However, a significant gender main effect was found for social support at post-treatment, with females reporting more social support than males. A significant gender x ethnicity interaction was also found for post-treatment control, with African-American females exhibiting higher levels of control than the other groups. Finally, a significant gender x treatment condition was found for negative mood, with males in the comprehensive group reporting more affective distress than those in the standard group. In this study, control appeared to be an integral factor in the chronic pain sample and greatly improved with comprehensive multidisciplinary treatment; while other areas of relative efficacy were not confirmed in this population.

A osteoartrite (OA) é uma doença que afecta que afecta todos os mamíferos, com uma expressão clínica e económica muito importante. No cão, a sua fisiopatologia clínica, médica e terapêutica são muito semelhantes às do Homem, tornando esta espécie num modelo natural de excelência para o estudo da OA no Homem. Associando-se a doença predominantemente ao aparecimento de sinais e sintomas clínicos envolvendo a(s) articulação(ões) afetada(s), o uso de terapêuticas locais administradas por via intra-articular (IA), possibilitam reduzir a quantidade da substância activa a utilizar para obter o efeito médico desejado, assim como os potenciais efeitos sistémicos colaterais. Desde há muito tempo que o uso de corticosteróides e ácido hialurónico têm assumido um papel relevante na terapia IA da OA. Actualmente, terapias inovadoras como o uso de concentrados de plaquetas autologas ou de anabolizantes, como o Estanozolol, têm-se revelado promissoras no controlo local da doença. Contudo, os seus mecanismos de ação não estão ainda totalmente esclarecidos, o que se traduz na dificuldade em obter consenso entre os clínicos para o estabelecimento de protocolos padronizados, fazendo-se assim a sua utilização com base na medicina de evidência resultante da experiência individual do clínico. A monitorização da OA no que respeita à sua evolução e resposta à terapeutica instituída é actualmente monitorizada com o recurso a marcadores de inflamação, técnicas de imagem como a radiografia e termografia digitais, ao estudo e análise da biomecânica do doente em placas ou plataformas de força, que adicionam informação muito importante à colhida durante o exame clínico objectivo do doente. O presente estudo realizado na espécie Canis familiaris com OA na articulação coxofemoral apresenta como principais objetivos: 1) Determinar o efeito de quatro substâncias administradas por via IA no maneio da OA da anca; 2) Avaliar a variação na concentração dos marcadores inflamatórios Proteína C-Reativa (PCR) e Interleucina-1 (IL-1) no líquido sinovial de doentes com OA coxofemoral; 3) Avaliar a relação entre a medicina laboratorial, a medicina de imagem e o exame médico objectivo do doente; 4) Validar o uso da termografia digital e da plataforma de pressão na avaliação da OA; e 5) Delinear um protocolo terapêutico para os doentes com OA coxofemoral utilizando o cão como modelo animal, sob o conceito geral de - Uma Única Saúde (One Health). O estudo foi desenvolvido numa amostra de cem articulações coxo-femorais (N = 100), de doentes com OA de ocorrência natural. A amostra estudada foi dividida aleatoriamente em cinco (5) grupos cada um com vinte (20) articulações, de acordo com o tipo de terapêutica IA administrada. Assim, consideraram-se: grupo de controlo (GC, n=20), grupo de hexacetonido de triancinolona (THG, n=20), grupo de concentrado de plaquetas (Grupo PCG, n=20), grupo de estanozolol (SG, n=20) e o grupo de acido hialurónico - Hylan GF 20 (HG, n=20). Cada doente foi avaliado em nove (9) tempos diferentes ao longo do estudo: dia 0 (dia do tratamento) e dias 8, 15, 30, 60, 90, 120, 150 e 180 após tratamento. As avaliações de cada doente e articulação foram realizadas com a análise da biomecânica do doente em plataforma de força, goniometria da articulação (amplitude articular em flexão e extensão), perímetro da coxa, termografia digital, radiografia digital, análise do líquido sinovial e quatro instrumentos de metrologia clínica, nomeadamente: Escala Rápida de Avaliação de Dor Canina (Canine Brief Pain Inventory), Escala de Osteoartite Canina de Liverpool (Liverpool Osteoarthritis in Dogs), Índice Ortopedico Canino (Canine Orthopedic Index) e Escala Analógica Visual de Hudson (Hudson Visual Analogue Scale). O trabalho estatístico dos dados foi realizado com o programa IBM SPSS Statistics version 20. Foram realizados vários testes estatísticos, de acordo com a análise pretendida: teste t de amostras emparelhadas, ANOVA de medidas repetidas, com correcção Huynh-Feldt, ou o teste de Wilcoxon. O teste de Kaplan-Meier, comparado com o teste log-rank, e a regressão de Cox foram conduzidos para avaliar sobrevivência. Todos os resultados obtidos forma considerados como estatisticamente significativos para o valor de P<0,05. Os grupos PCG e HG foram aqueles que registaram melhorias mais significativas e duradouras, de acordo com os resultados da regressão de Cox para as diferentes avaliações realizadas. Considerando as avaliações objectivas, PCH e HG apresentaram uma melhora de 81% e 69%, e de 61% e 57% para os índices de simetria e diminuição de suporte de peso em estação, respetivamente. De acordo com os resultados obtidos, o uso de concentrado de plaquetas autologas e de ácido hialurónico de alta densidade parecem ser os tratamentos preferenciais para a melhoria das alterações registadas nos doentes com OA, melhorando a qualidade de vida dos doentes. Os resultados obtidos permitiram verificar também uma redução no nível da dor nos doentes do grupo THG, o que pode ser atribuído ao marcado efeito anti-inflamatório dos corticosteróides; Title: Evaluation of the efficacy of four intra-articular therapeutic protocols for the control and treatment of osteoarthritis in a Canis familiaris model. ABSTRACT: Osteoarthritis (OA) affects all mammals, being an important and costly disease. The pathologic process, clinical presentation, and response to treatment are very similar in humans and dogs, making the naturally occurring canine osteoarthritis model the closest to a gold standard for the study of human osteoarthritis. Since OA is mainly symptomatic in the affected joint while lacking obvious extra-articular manifestations, it is well suited to have a local therapy administered by intra-articular (IA) injection, reducing the total amount required to produce an effect as well as systemic adverse effects. There are several substances used in the IA management of OA, some used for a long time, like corticosteroids and hyaluronan, while others have gained more recent attention, as autologous platelets and stanozolol. In common, regardless of how long they have been used, their action mechanisms and effects are not fully known, as the protocol for their use is usually based on the clinician’s individual experience. Disease evolution and response to treatment can be monitored through inflammation markers, different clinical evaluation modalities, as digital thermography, digital radiography, or stance analysis, which all add relevant information to the clinical examination. This study set four goals: 1) to determine the effect of four IA substances in the management of hip OA; 2) assess variations in C-reactive protein and IL-1 in the synovial fluid of patients with OA; 3) evaluate the relationship between laboratory medicine, with imaging results and clinical assessment; 4) validate the use of digital thermography and weight bearing evaluation in OA assessement; and 5) to outline a treatment protocol for patients with OA, with the dog as an animal model, under the One Health concept. One hundred (N=100) hip joints were selected from patients with naturally occurring osteoarthritis and randomly assigned to five groups: control group (CG, n=20), triamcinolone hexacetonide group (THG, n=20), platelet concentrate group (PCG, n=20), stanozolol group (SG, n=20) and Hylan G-F 20 group (HG, n=20). Evaluations were conducted on days 0 (treatment day), 8, 15, 30, 60, 90, 120, 150, and 180 days post-treatment. They consisted of the evaluation of weight distribution, joint range of motion at flexion and extension, thigh girth, digital thermography, radiographic signs, synovial fluid analysis, and four clinical metrology instruments were collected: Canine Brief Pain Inventory, Liverpool Osteoarthritis in Dogs, Canine Orthopedic Index and the Hudson Visual Analogue Scale. All results were analyzed with IBM SPSS Statistics version 20. Several statiscal tests were conducted, according to the intended analysis: Paired Samples T-Test, Repeated Measures ANOVA, with a Huynh-Feldt correction, or Wilcoxon Signed Ranks Test. Kaplan-Meier estimators were conducted and compared with the log-rank test. Cox proportional hazard regression analysis was performed to determine treatment survival. A significance level of P<0.05 was set. PCG and HG registered longer lasting effects, and better improvements according to the Cox hazard regression with the different assessments made. Considering objective parameters, PCH patients showed a 69%-81% improvement in symmetry and weight-bearing reduction, respectively, while HG showed 61% and 57% improvements. These seem to be the preferred treatments for functional impairments due to OA. In addition to these evaluations, PCG and HG also registered more significant improvements in several scores as Hudson Visual Analogue Scale, stiffness, function, gait of the Canine Orthopedic Index. Better impact on pain interference was observed in THG, which could be attributed to the high anti-inflammatory effect of corticosteroids, and the relation between pain and inflammation.

Even today, with modern medicine and technology, post-operative pain still exists as anmajor issue in modern treatment. A lot of research efforts have been made, in order toimprove pain outcome for patients that has undergone surgery[18][15].Even though physician's and doctors are well educated, the success rate is aboutapproximately 70 %, still there are patients that experience severe pain, after they haveundergone surgery. There could be several reasons to this, for example, lack of methods orsupport should be amongst other things, factors to consider[18].The problem has been to initiate a case-library and eventually create a tool, that could aidphycisians or doctors in their decision making, which hopefully would help in improvingpain outcome. The chosen method to do this, is a modified version of the CBR-algorithm,which is an artificial intelligence algorithm. The CBR-algorithm makes use of features,solution and outcome, and is implemented with a simple prototype, as a similarity function.The are several reasons for why this method was chosen, but using this method makes itpossible to easily create a web-based tool, so it can easily be accessed from anywhere, butstill be effective and work as a support tool.The algorithm works as a self learning mechanism, and is easy to implement, and theinterface has been constructed, allowing the phycisian or doctor to retrieve informationabout patients and run CBR. The desired results are as expected, it's possible to run theCBR, retrieve and compare cases, and get suggestion of solution or action that should beperformed.The conclusion that can be made, is that, although this is a very basic working medicalapplication, still an overall improvement is needed in order to be used as a medicalapplication. It's anyhow a start. For more details and information, check the appendicesplease.
The PainOut Project

"December 2001" Includes bibliography. In the light of a general concensus that in the treatment of pain, patients with a prior history of substance abuse (particulary opioid dependence) appear to be at increased risk for pain mismanagement problems, this thesis aims to produce data that will eventually help in the formulation of prescribing guidelines, improved policies, and help direct optimal acute pain management for methadone maintenance patients.

Shoulder pain is very common, affecting 14-21 % of the population at some time during their lifetime. The aims of this thesis were to improve the understanding of various aspects concerning the pathogenesis and treatment of subacromial pain and rotator cuff tears. Patients and healthy individuals were examined and compared in five studies: Study I) Seventy patients were retrospectively examined, clinically and with ultrasound, 15 years after arthroscopic subacromial decompression. All patients had an intact rotator cuff at surgery. Ultrasound showed significantly fewer rotator cuff tears compared to the prevalence of asymptomatic tears reported in the literature for the same age group. This indicates that arthroscopic subacromial decompression might protect the rotator cuff. Study II) Forty-two patients were retrospectively examined, clinically and with ultrasound, 39 months (mean) after an acute rotator cuff repair. All patients had pseudoparalysis after trauma, a full thickness tear and no previous history of shoulder symptoms. A delay in surgical treatment of three months and the number of tendons injured did not affect the outcome. Age affected outcome negatively. Study III) Plasma samples from 17 patients with cuff tears and 16 plasma samples from healthy age- and gender-matched controls were collected and analysed regarding the levels of matrix metalloproteinases and their inhibitors, TIMP1-4. Elevated levels of TIMP-1 were found in the patients with cuff tears compared to controls. Higher levels of TIMP-1, TIMP-3 and MMP-9 were found in patients with full-thickness tears compared to patients with partial-thickness tears. Study IV) Ninety-seven patients with longstanding subacromial pain, on the waiting-list for arthroscopic subacromial decompression, were prospectively randomised to specific shoulder exercises or control exercises for three months. Thereafter they were clinically examined and asked if they still wanted surgery. The specific shoulder exercises focusing on eccentric exercise for the rotator cuff and scapula stabilisers were found to be effective in reducing subacromial pain and improving shoulder function, thereby reducing the need for surgery. Study V) All patients including those operated, in Study IV were re-examined after one year using clinical assessment scores. The option of surgery was continuously available up to the one-year follow-up. Ultrasound and radiological examinations performed at inclusion were analysed in relation to the choice of surgery. The positive effects of the specific exercise programme were maintained after one year and significantly fewer patients in this group chose surgery. Surgery was significantly more often chosen by patients who had a low baseline shoulder score, and/or a full thickness rotator cuff tear.  All patients showed significant improvement in the clinical scores one year after inclusion or one year after surgery. These results support the concept that subacromial pain has a multifactorial aetiology and that the first line of treatment should be specific shoulder exercises. When conservative treatment fails, an acceptable result can be achieved with arthroscopic subacromial decompression. The rotator cuff status is important to consider when treating and studying these patients.

Chronic pain and pain management are frequently discussed and debated topics in American medicine today. The patients’ understanding of treatment options for management of chronic pain is a less frequently discussed topic. The purpose of this study is to explore patient perceptions of chronic pain treatment options. The framework for guiding this study was Neuman’s Systems Model (1995) based on the concepts of stress, client stability, and intervention. A review of the literature was completed that revealed very little information on the topic and therefore further research regarding patient perceptions of treatment options for chronic pain was warranted. Nine patients participated in interviews and shared their experiences with treatment options and contexts or situations that influenced or affected those experiences of treatment options. Participants described their experience with chronic pain to include options available to them; the effectiveness of the methods tried; lifestyle changes associated with their pain; feelings of hopelessness for the future relative to pain resolution as well as available options; the effects of listening and understanding; and depression.

Thesis (M.S.)--University of North Carolina at Chapel Hill, 2008.
Title from electronic title page (viewed Sep. 16, 2008). "... in partial fulfillment of the requirements for the degree of Master of Science in the School of Dentistry Orthodontics." Discipline: Orthodontics; Department/School: Dentistry.

Background: Pain is a common and unwanted side effect of orthodontic treatment, caused by a reduction in blood flow during tooth movement using orthodontic appliances. Pain has been shown to be the most common reason for patients wanting to discontinue treatment. Pharmacological methods of pain relief have been investigated in the literature showing promising results, although there remains some uncertainty among orthodontists as to which painkillers are most suitable and whether pre-emptive analgesia is beneficial and therefore present as a simple intervention to prevent this unwanted side effect of treatment. Therefore a Cochrane review is warranted to assess and summarise the international evidence. Objectives: To determine the most effective drug intervention for pain relief during orthodontic treatment. Search methods: We searched the following databases up to August 2016: Cochrane Oral Health Group Trials Register, Cochrane Pain, Palliative and Supportive Care Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, EMBASE via Ovid and CINAHL via EBSCO. We searched the US National Institutes of Health Trials Registry, and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on language or date of publication when searching databases. Selection criteria: We included randomized controlled trials (RCTs) relating to pain control during orthodontic treatment measured on a visual analogue scale (VAS), numerical rating scale (NRS) or any categorical scale. Data collection and analysis: Two reviewers independently extracted information regarding methods, participants, interventions, outcomes, harms and results, independently and in duplicate. The Cochrane risk of bias tool was used to assess the methodological quality of the studies. Main results: 22 RCTs were identified which included 2110 participants. A meta-analysis was carried out on twelve papers that compared analgesics versus control, nine that compared NSAIDs versus paracetamol and two comparing pre-emptive versus post-treatment ibuprofen for pain control following orthodontic treatment. Analgesics were found to effectively reduce pain at 2, 6 and 24 hours following orthodontic treatment (mean difference -24.48, 95% CI -30.54 to -18.43, P= < 0.00001). No difference was found between the efficacy of NSAIDs and paracetamol, except low quality evidence that paracetamol is more effective at reducing pain associated with initial archwire placement at 2 hours (MD 14.63, 95% CI 0.77 to 28.50, P=0.04). Pre-emptive ibuprofen gives better pain relief at 2 hours (MD -11.33, 95% CI -16.09 to -6.58, P= < 0.00001) however the effect reduces over time. No difference was found between the use of topical NSAIDs and local anaesthetic. However overall quality of evidence was poor and levels of heterogeneity were variable (I2 results varied from 0% to 87%). Authors' conclusions: Analgesics are effective at reducing pain following orthodontic treatment. There is no difference between the efficacy of systemic NSAIDs and paracetamol, or topical NSAID and local anaesthetic. Pre-emptive ibuprofen gives better pain relief at 2 hours however the effect reduces over time. More high quality research is needed to investigate the effect of NSAID and paracetamol and the effect of pre-emptive and post-treatment administration of analgesics for orthodontic pain.

Thesis (M.A.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
Recent studies have shown the efficacy and practicality of the integration of complementary and alternative therapies and biomedical treatments for various diseases and illnesses, including high blood pressure, diabetes, epilepsy, and cancer. Saper et al. (2013) demonstrated that once-weekly yoga classes were equally as effective for relieving chronic low back pain in low-income, minority populations than twice-weekly yoga classes. Pain medication data collected from this 12-week study was used to examine the effect of yoga on analgesic use. Pain medications were categorized into four major groups: (1) acetaminophen, (2) opiates, (3) non-steroidal anti-inflammatory drugs (NSAIDS), and (4) other. The average number of NSAID pills taken daily decreased from baseline to 12 weeks. In addition, there was no statistically significant difference in the average number of any type of analgesic taken between once- and twice-weekly yoga groups from baseline to 12 weeks. Our findings suggest that yoga is most useful for individuals with mild to moderate chronic low back pain; however, further studies with more powerful sample sizes must be conducted in order to make more precise conclusions.
2031-01-01

Very little work has been undertaken that explores pain as a part of human existence and the inherent knowledge that accompanies it. What pain means to people and how they know their own pain is the subject of this research study.The research sought to identify ways of knowing cancer pain of six participants, each receiving palliative care at the time of this study. The themes of, balancing conflict, living with threat, always there and making sense are identified and examined to provide understanding of the ways these people know their pain. A new model of pain assessment is offered that incorporates an ontological way of knowing, and the meaning that the findings have for nursing practice is explored. Implications for nursing practice and education that are derived from the study are offered. The rigour of the study is promoted through an audit process
Doctor of Philosophy (PhD)

Animal models are crucial to improve the knowledge of the mechanisms underlying the different pathological processes. These models are also excellent tools to facilitate the research of new targets for the treatment of different diseases and to evaluate the benefit/risk ratio of the potential new treatments. We have focussed this research work in the study of a new potential targets for pain, cognitive and eating disorders using new animal models developed in our laboratory. We first investigated the effects of the interaction between cannabinoids and nicotine on cognitive processes and metabolism using different behavioural models and new experimental devices. In a second part of this work, we investigated new therapeutic targets for neuropathic pain and for this purpose we developed a new behavioural model to improve the study of the therapeutic potential and possible side-effects of novel compounds.
Los modelos animales son cruciales para mejorar el conocimiento sobre los mecanismos que constituyen la base de los diversos procesos patológicos. Estos modelos representan también excelentes herramientas para facilitar la investigación de nuevas dianas para el tratamiento de estas enfermedades y para evaluar el cociente beneficio/riesgo de los nuevos tratamientos potenciales. Este trabajo de investigación se encuentra centrado en el estudio de nuevos dianas terapéuticas para el dolor, los procesos cognitivos y los desórdenes alimentarios utilizando nuevos modelos animales desarrollados en nuestro laboratorio. En primer lugar, hemos investigado los efectos de la interacción entre los cannabinoinoides y la nicotina a nivel los procesos cognitivos y del metabolismo usando diversos modelos comportamentales y nuevos dispositivos experimentales. En una segunda parte de este trabajo, hemos estudiado nuevas dianas terapéuticas para el dolor neuropático y hemos desarrollado para este propósito un nuevo modelo comportamental que permite evaluar el potencial terapéutico y los posibles efectos secundarios de nuevos compuestos.

All people experience pain and for some people, acute pain may over time develop into long-term disabling problems. Already at an early stage, it is possible to identify people at risk for long-term problems and psychologically oriented interventions have been shown to successfully prevent future disability. However, not all people are helped by treatment and there is room for improvement. Moreover, subgroups of people suffering from pain, with different profiles of psychological factors have been identified, indicating that people with pain problems differ. The first aim of this dissertation was to improve the understanding of how people differ. The second aim was to use these individual differences and to match people to psychological treatment based on their psychological profile. The third aim was to explore what happens during treatment that might be important for treatment outcome. The findings show that people who belonged to subgroups with elevated levels of psychological factors had less favorable outcomes over time, despite treatment, than people with no elevations. Moreover, people with elevations in several psychological factors had even less favorable outcomes. Psychological treatments aimed at preventing future disability performed well, but using profiles to match people to treatment did not improve outcomes further; people who were matched to a treatment and people who were unmatched had similar outcomes. However, the profiles used for matching were unstable over time and there is need to improve the identification of psychological variables used for treatment matching. Finally, a number of psychological factors were shown to be valuable targets for treatment; if the treatments successfully produced change in people’s thoughts and emotions related to pain the treatment outcomes were better. The findings were summarized in a flow chart showing the recommended clinical approach to people seekinghealth care for acute pain problems.

Subacromial pain is the most common problem among patients with shoulder complaints seeking primary care. The recommended treatment for these patients is primarily non-surgical with a focus on exercise treatment. If this treatment fails arthroscopic subacromial decompression (ASD) followed by exercise treatment is recommended. Surgical treatment with ASD has increased substantially in Sweden in recent years even though studies comparing exercise treatment with surgery report equally positive results. Still, there is a need of evidence based preand postoperative exercise treatments, standardised and described in detail, to guide treatment of these patients in clinical practice. The overall aim of this thesis was to evaluate the efficacy of pre- and postoperative exercise strategies on shoulder function and how the preoperative strategy affects the need for surgery in patients with long-standing subacromial pain. This thesis comprises four papers which are based on two randomised controlled trials. In study A, patients were randomised after ASD surgery to either physical therapist (PT) supervised strength-endurance exercises for the rotator cuff and scapula stabilisers or to home-based movement exercises for a period of three months. Shoulder function and pain, health related quality of life and return to work was evaluated for 6 months (paper I). In study B, patients on the waiting list for surgery were randomised to either specific exercise strategy with strengthendurance exercises for the rotator cuff and the scapula stabilisers or to control exercises with movement exercises for the neck and shoulders for a period of three months. After completing the exercise program and also after 12 months, shoulder function and pain, need for surgery and health related quality of life was evaluated. Baseline shoulder function, rotator cuff status and radiological findings were analysed in relation to the choice of surgery (paper II, III). The minimal important clinical change (MIC) of the Constant-Murley (CM) score, used as primary outcome in this thesis, was determined by using a visual anchor-based MIC distribution method (paper IV). Six months after ASD surgery, patients who performed PT-supervised strength-endurance exercises improved significantly more in shoulder function and pain compared to patients who had performed home-based movement exercises (paper I). Patients on the waiting list for surgery who performed specific strength-endurance exercises had significantly greater improvements in shoulder function and pain compared to patients performing movement exercises (paper II). A significantly lower proportion of those performing specific strength-endurance exercises chose surgery at the three- and 12 months follow-ups (paper II, paper III). Low baseline values in shoulder function and pain measured with the CM score and/or having a full thickness rotator cuff rupture were associated with an increased risk of choosing surgery (paper III). Regarding the CM score, a change between 17-24 points seems to be clinically important for patients with long-standing subacromial pain (paper IV). Supervised strength-endurance exercises seem to be more effective than home-based movement exercises after ASD surgery. For patients on the waiting list for surgery, the specific strategy of strength-endurance exercises was effective in improving shoulder function and pain and the need for surgery was reduced at 12 months. Low baseline values for shoulder function and pain measured with the CM score and/or having a full thickness rotator cuff tear seem to be predictors for choosing surgery. The CM score is able to detect the MIC in individual patients with long-standing subacromial pain when the rotator cuff is intact. In all patients with longstanding subacromial pain, the MIC value was dependent on the subgroup as well as the choice of statistical analysis.

Chronic neuropathic pain (CNP) occurs as a consequence of injury to the nervous system. Despite recent advances, CNP lacks objective diagnostic criteria, is often unrelenting and refractory to treatment. The primary aims of this thesis are twofold; the identification of CNP biomarkers using both human cohorts and an animal model (spinal nerve ligation; SNL) of neuropathic pain, and to provide clarity on the role of GTP cylcohydrolase I (GCH1) in CNP. Analysis of GCH1 and related genes and metabolites was conducted. As biomarkers, nitrite/nitrate and neopterin did not differentiate controls from CNP patients. However, significant differences were observed with biopterins, whilst correlations were observed between GCH1, nitrite/nitrate and neopterin, which were notably stronger in patients than controls. Analysis in human cohorts and in the SNL model also inferred that downregulation of GCHFR may contribute to BH4 synthesis. In order to provide clarity on the role of the GCH1 pain protective haplotype, reporter gene assays were used. This demonstrated a potential regulatory role for the GCH1 5’ SNP (rs8007267). In silico prediction of transcription factor binding sites suggested that this may be mediated by the aryl hydrocarbon nuclear translocator. The use of electrophoretic mobility shift assays showed strong specific binding with probe pertaining to the major allele. Further analysis is required to elucidate transcription factor binding, potentially facilitated by 2D-PAGE and mass spectrometry. In order to further elucidate potential CNP biomarkers, microarray analysis and qRT-PCR were performed using blood obtained from CNP patients. Data refinement led to the isolation of 27 potential CNP biomarkers, of which several cross-validated between cohorts. Microarray data, literature evidence, and correlations with previous microarrays provided evidence suggestive of a role for TIMP1. Multiple other genes, including CASP5, TLR4, TLR5, MC1R and CX3CR1, were differentially regulated in CNP. Genes surviving microarray data refinement were subsequently analysed in the dorsal horn of Sprague Dawley and Wistar Kyoto rats after SNL. Several genes, including Dpp3, Mc1r and Timp1, were similarly differentially expressed in the rodent SNL model, which suggests that these genes may be involved in the pathophysiological mechanisms of CNP, and may also function as potential translational biomarkers of CNP. This work provides multiple avenues for expansion and further investigation. Clearly, the challenges associated with biomarker discovery in CNP states are considerable, though it is hoped that this thesis provides valuable insight and the necessary foundation for future work.

The World Health Organization describes over 80% of the world's population as living without adequate access to treatment for pain. Improvement initiatives focus largely on the field of palliative care and on increasing access to opioid medications. Predominantly, they are led from the global North while targeting healthcare provision in the global South. I propose that the limited improvement seen from these programmes is in part, attributable to their narrow clinical focus and to a lack of understanding of practice at the local level. Using India as a single case of study, the aim of this research project is to assess critically how medical practitioners, working within and outwith palliative care, treat patients in pain. My research questions address the practice of pain management and clinicians' evaluations of this care, from the perspective that pain as a medical problem, is a professionally constructed phenomenon. In this cross-disciplinary research, I use mixed methods, combining qualitative and quantitative data, from interviews and surveys administered to clinicians, field observations in India and secondary analysis of a pre-existing oral history archive. I draw on theories of the policy process, postcolonialism and social constructionism. Through critically evaluating practice, I move beyond more familiar descriptions of care delivery and barriers to improvement, to understand how these issues are framed, formed and contested. The study demonstrates salient features of the Indian healthcare system: scarce resources, multiple providers, weak regulation, and the dominant role of the private sector. The availability of treatments, including opioids and non-pharmacological therapies, is low and variable. The framing of pain as a problem requiring medical treatment is ubiquitous and there is consensus regarding the need to improve the delivery of clinical care. There is variation, however, in opinions about how this should be achieved, particularly with respect to the choice of treatment modality. Power is wielded by clinicians in the form of knowledge, and is negotiated with other medical professionals, politicians and patients. In conclusion, although Indian clinicians' descriptions of individual practice recognise the unique local factors that impact on the delivery of pain management, their proposed strategies for improvement emphasise increasing the provision of medical treatments developed in the global North. There is, however, little acknowledgment of the assumptions and limitations of this western medical model when used to treat pain in India.

Orofacial pain is associated with various pathologies such as headache, dental pain and ophthalmic pain. The trigeminal system innervates a large section of the head, including the nasal and oral cavities, the cornea and facial skin, and is responsible for the transmission of pain signals from the orofacial regions to the brain. These investigations were undertaken to study the effect of intranasal delivery of analgesics on orofacial pain using an operant testing method in mice. Doses of either lidocaine HCl or butorphanol tartrate were administered to mice, and the analgesic effectiveness was measured using a thermal operant behavior test involving a facial heat stimulus. Two parameters were measured in the operant assay: the number of licks and the duration of facial contact. Pain response was measured at two different temperatures: 37 ºC and 49 ºC. The magnitude of analgesic response was also compared between intranasal and intraperitoneal drug administration at 49 ºC. Mice showed a significant decrease in the number of licks and duration of facial contact for both treatment and control groups as the temperature was increased from 37 ºC to 49 ºC. A significant difference in the duration of facial contact was observed following either lidocaine or butorphanol by nasal administration. One group of animals receiving intranasal lidocaine did exhibit an increase in the duration of facial contact compared to the control. Two doses of butorphanol were tested and increases in the duration of facial contact were observed at both levels, but no significant difference was observed in the number of licks recorded. No convincing differences were observed in the mice behaviors for intranasal or intraperitoneal dosing of lidocaine or butorphanol. This suggests that nasal administration of these two analgesics at the doses tested did not provide superior pain relief compared to systemic delivery of the agents.

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.

Objectives: To explore the pain mechanism and the origin of the pain and to evaluate a short-term pain relief treatment in women suffering from CPP persisting after childbirth in order to enable physiotherapeutic intervention. Material and methods: Thirty-six parous women with chronic pelvic pain persisting after childbirth were recruited at the Department of Physiotherapy, SundsvallHospital and by advertisements in newspapers and 29 parous women without chronic pelvic pain were recruited from an organized gynaecological screening at a midwifery surgery. All women were provoked by intra-pelvic palpation of 13 predetermined intra-pelvic landmarks. The provoked pain distribution was expressed in pain drawings and the pain intensity verbally on a Likert scale.Also, in a randomised controlled trial the 36 women with chronic pelvic pain were allocated to bilateral injection treatment with either triamcinolone or saline solutions, given once on the ischial spine with follow-up after four weeks. Results: Referred pain provoked on intra-pelvic landmarks follows a specific pattern. In general, pain provoked by palpation of the posterior intra-pelvic landmarks was mostly referred to the sacral region and pain provoked by palpation of the ischial and pubic bones was mostly referred to the groin and pubic regions. In women with chronic pelvic pain the provoked pain distribution area and pain intensity were magnified as compared to women without chronic pelvic pain. In the clinical trial decreased pain intensity, decreased distribution of pain and improved physical function was achieved among the triamcinolone treatment group as compared to the saline treatment group. Also, a positive correlation was shown between reduced pain intensity and improved function. Conclusions: Referred pain patterns provoked on intra-pelvic landmarks in women with chronic pelvic pain persisting after childbirth are consistent with sclerotomal sensory innervations and indicates allodynia and central sensitisation. This suggests that pain mapping can be used to evaluate and confirm the pain experience and contribute to diagnosis. Also, the pain intensity provoked by stimulation of the intra-pelvic landmarks is suggested to be useful to differentiate women with chronic pelvic pain from those without. Corticosteroid treatment to the ischial spine resulted in decreased pain and increased function.

Smerter er et fryktet symptom hos pasienter med kreft og deres pårørende. 80 % av pasienter med langtkommet kreft opplever kreftsmerter, og hele 10-30 % opplever smerte og/eller uakseptable bivirkninger til tross for behandling med et sterkt opioid som for eksempel morfin. Hos disse pasientene er et bytte til et annet opioid som metadon et behandlingsalternativ. Mange strategier for opioid-bytte til metadon er foreslått, men ingen randomiserte studier eksisterer. Et alternativ er stopp-og-start-metoden hvor en starter rett på ny metadondose samtidig som det første opioidet avsluttes. Det er hevdet at pasientene da får raskere smertelindring (raskere stabil metadon konsentrasjon) og at bivirkningene forsvinner raskere (raskere eliminasjon av det første opioidet og metabolitter) enn ved 3-dagers-metoden hvor det nåværende opioidet trappes ned over tre dager, og overlappes med tilsvarende dose metadon hver dag. En stor andel av pasienter med langtkommet kreft opplever plutselige episoder med intense smerter av relativt kort varighet til tross for at opioider lindrer bakgrunnsmerten effektivt; såkalte gjennombruddsmerter. Standard behandling for gjennombruddsmerter har vært ”hurtigvirkende” opioid-tabletter som morfin ved behov. På grunn av lang tid til effekt og langsom utskillelse fra kroppen har effektprofilen til opioid-tabletter passet dårlig med gjennombruddsmertenes tidsprofil. Det ideelle medikamentet mot gjennombruddsmerte tas raskt opp, har rask tid til effekt, skilles raskt ut og må kunne håndteres av pasienten selv. Fentanyl er et svært potent opioid (kan gis i små volum), er fettløselig (tas raskt opp gjennom nesen) og har rask tid til effekt. Målet for denne avhandlingen var 1) å teste hypotesen om at stopp-og-start-metoden ved bytte fra morfin/oksykodon til metadon hos kreftpasienter med smerter/bivirkninger er mer effektiv og like sikker som 3-dagers-metoden ved å måle smerteintensitet, bivirkninger, opioidkonsentrasjoner og alvorlige hendelser og 2) å studere farmakokinetikken til fentanyl gitt som nesespray og toleransen for medikamentet i målgruppen. Farmakokinetiske parametre fra arterielle og venøse blodprøver ble også sammenliknet. 42 kreftpasienter på morfin/oksykodon-behandling fra fire sykehus i Norge ble randomisert til å bytte til metadon på en av to måter; stopp-og-start-metoden eller 3- dagers-metoden. Beregnet metadondose var avhengig av morfin/oksykodon dosen de sto på. Smerteintensitet ble registrert av pasientene før intervensjon, samt dag 3 og 14. Bivirkninger, alvorlige hendelser og opioiddoser ble registrert daglig i 14 dager. Det ble også tatt blodprøver før opioid-byttet (dag 1), dag 2, 3, 4, 7 og 14 til analyser av morfin (med aktiv metabolitt M6G), oksykodon og metadonkonsentrasjoner. To studier med fentanyl nesespray ble gjennomført. I den første ble 19 kreftpasienter med gjennombruddsmerter fra tre land ble randomisert til 2 av 3 doser (50, 100 eller 200 µg) med fentanyl nesespray. Blodprøver til fentanyl konsentrasjonsanalyser ble tatt 15 ganger ila 5 timer etter administrasjon på to forskjellige dager. Vitale funksjoner som respirasjon, oksygen- metning i blodet og blodtrykk ble registrert. I den andre studien fikk 12 mannlige pasienter som skulle til prostata eller blære operasjon, og som ikke brukte opioider fra før, en dose med 50 µg fentanyl nesespray. Den første timen etter at sprayen var gitt, ble 13 blodprøver tatt fra både arterier og vener. I tillegg ble tolerabilitet og vitale funksjoner registrert. Resultatene i denne avhandlingen viser at de pasientene som byttet til metadon med stopp-og-start-metoden ikke rapporterte lavere smerteintensitet enn pasientene i 3-dagersgruppen, til tross for at de var mer eksponert for metadon de tre første dagene etter byttet. Det var ingen signifikant forskjell mellom gruppene i antall pasienter som hadde stabile metadonkonsentrasjoner dag 4. Pasientene i stopp-og-start- gruppen rapporterte heller ikke mindre bivirkninger, tross mindre eksponering for morfin, M6G og oksykodon de første tre dagene, enn i 3-dagers-gruppen. Det var signifikant flere som falt ut av studien (11 mot 3) og tre alvorlige hendelser (to døde og en hadde alvorlig respirasjons depresjon) i stopp-og-start-gruppen sammenliknet med 3-dagers-gruppen. Dette indikerer at stopp-og-start-metoden ikke er sikker for denne pasientgruppen med langtkommet kreft og høye opioiddoser. Resultatene indikerer at et bytte over tre dager hos kreftpasienter med høye opioiddoser er ønskelig, og at pasientene må observeres i mer enn fem dager ved bytte til metadon uavhengig av metode. Nasalt fentanyl ble godt tolerert både av pasienter som brukte opioider og de som ikke brukte opioider fra før. Fentanyl ble raskt tatt opp i blodet fra neseslimhinnen (venøse prøver 9-15 min og arterielle prøver 7 min), slik at disse studiene støtter forventningen om at fentanyl nesespray kan være velegnet for å behandle kreftrelaterte gjennombruddsmerter. Arteriell maksimum konsentrasjon var to ganger høyere og tid til maksimum konsentrasjon var 5 min kortere enn i venøse prøver, og de korrelerte ikke. Det er det arterielle blodet som forsyner hjernen med fentanyl, og arterielle prøver vil være mer presise når man skal forsøke å anslå tid til smertelindrende effekt.
Pain is a symptom feared by cancer patients and their relatives. 80 % of patients with advanced cancer experience cancer pain, and as much as 10-30 % experience pain and/or acceptable adverse effects despite treatment with a strong opioid such as morphine. A switch to methadone is an alternative in these patients. Several switching strategies to methadone have been proposed, but no randomized trials are performed. The stop and go procedure in which the initial opioid is stopped and methadone is started is believed to give a shorter time to pain relief (a shorter time to stable methadone concentrations) and ease of adverse effects more rapidly (a fast elimination of the initial opioid and metabolites) than the 3-days switch in which the current opioid is gradually reduced over three days, and the methadone dose increased in corresponding doses. A majority of patients with advanced cancer experience a sudden onset of intense pain with short duration despite effective treatment of the background pain; breakthrough pain (BTP). The standard treatment of BTP has been “short-acting” opioid tablets such as morphine taken by mouth as needed. Because of a long time to effect and a slow elimination from the body, the effect profile of opioid tablets has not been corresponding with the characteristics of BTP. The ideal drug for BTP is rapidly absorbed (short time to effect) and eliminated, and it should be easy to administer for the patients. Fentanyl is an extremely potent (it can be administered in small volumes), it is fat-soluble (rapidly absorbed through the nasal mucosa) and has a fast onset of action. The aims of this thesis were to test the hypothesis that the stop and go method when switching from morphine/oxycodone to methadone in cancer patients with pain/adverse effects is more effective than, and as safe as the 3-days switch by measuring pain intensity, adverse effects and opioid serum concentrations of the respective opioids. Secondly, the aim was to study the pharmacokinetics of intranasal fentanyl, its tolerability, and safety in the target population. Pharmacokinetic parameters of fentanyl were compared between blood samples drawn from arterial or venous samples. 42 cancer patients on morphine/oxycodone in four hospitals in Norway were randomized to a switch to methadone by one of the two switching strategies; stop and go or the 3-days switch. A dose-dependent conversion ratio was used. Pain intensity was recorded by the patients at baseline, on day 3 and day 14. Adverse events and opioid doses were recorded daily for 14 days. Blood samples were drawn before the switch (day 1) and day 2, 3, 4, 7, and 14 for analyzes of morphine (with the active metabolite M6G), oxycodone and methadone concentrations. Two studies on nasal fentanyl were performed: 1) 19 cancer patients from three countries, treated with strong opioids and experiencing BTPs were randomized to 2 of 3 doses (50, 100 or 200 µg) of nasal fentanyl. Venous blood samples for fentanyl concentration analysis were drawn 15 times during the five hours after administration, and vital signs such as respiration, oxygen saturation in blood, and blood pressure, were registered on two different days. 2) 12 elderly, male patients scheduled for prostate or bladder surgery, not using opioids, received a dose of 50 µg of nasal fentanyl. Both arterial and venous blood samples were drawn 13 times, and tolerability and vital signs were recorded the first hour after administration. The results in this thesis show that the patients that switched to methadone by the stop and go method did not report lower pain intensity than those switched by the 3-days strategy, despite being exposed to more methadone the first three days after the switch. The number of patients with stable methadone concentrations day 4 was not significantly different in the two groups. Neither did the patients in the stop and go group report less adverse events, even though they had a lower exposure of morphine, M6G or oxycodone than the 3-days switch group, the first three days after the switch. Significantly more patients dropped out of the stop and go group (11 to 3), and there were three serious adverse events in this group (two died and one severe respiratory depression day 5) compared to the 3-days switch group. These findings indicate that the stop and go strategy is not safe in these patients with advanced cancer and high opioid doses. The 3- days switch is recommended in cancer patients on high opioid doses, and patients need to be observed for more than five days after the switch regardless of switching strategy. Nasal fentanyl was well tolerated by both opioid naïve and opioid tolerant patients. Fentanyl was rapidly absorbed from the nasal mucosa (venous 9-15 min and arterial 7 min). These studies support the expectation that nasally administered fentanyl is a possible treatment for breakthrough pain. Time to maximum concentrations of fentanyl was 5 min shorter and maximum concentrations twofold higher in the arterial samples compared to the venous samples, and these were not correlated. The arterial blood supplies the brain with fentanyl. Arterial samples are more precise when trying to predict time to pain relief.

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Bachelors
Health and Public Affairs
Nursing

Aims: The primary aim of this thesis was to explore the role of palliative radiotherapy in the treatment of pain in malignant pleural mesothelioma (MPM). The effect of radiotherapy on other symptoms was also examined. Biomarkers which might predict response to radiotherapy (Quantitative Sensory Testing – QST) were explored and objective evidence of response was sought via interpretation of Computed Tomography (CT) scans. The thesis also examined the role of Positron Emission Tomography (PET)-CT in radiotherapy planning and characterising pain in MPM. Methods: A narrative review of the challenges of pain management in MPM and a systematic review of the evidence supporting the use of palliative radiotherapy for pain control in MPM, were undertaken. In addition, a multi-centre, single arm phase II trial was conducted which examined the role of radiotherapy in pain control in MPM. This trial also assessed the role of PET-CT in radiotherapy planning and allowed for a characterisation of MPM-related pain. These components form the basis of this thesis. Results: Palliative radiotherapy at a dose of 20 Gy in five daily fractions using 6 Megavoltage (MV) photons improves pain in a significant proportion of patients with MPM. It does not have a beneficial effect on other symptoms or on quality of life. QST does not appear to be a useful clinical biomarker indicating likelihood of response to radiotherapy. Objective evidence of response via CT is low. Incorporation of PET-CT in the radiotherapy planning process alters the anatomical location of the target volume in patients with MPM. There is also an association between the Standard Uptake Value (SUV) uptake and pain, with the areas with highest SUV uptake being associated with the areas of pain. PET-CT results in upstaging of a significant proportion of patients. Pain is often severe and debilitating for patients with MPM and it has often a combination of neuropathic and nociceptive mechanisms. The presence of a neuropathic component to the pain is not associated with an increased likelihood of response to radiotherapy. Conclusions: Radiotherapy is effective at relieving pain in a proportion of patients with MPM and should be considered for all patients with MPM-related pain. PET-CT improves multiple parameters in the radiotherapy planning process compared with CT alone. QST parameters have not been shown to predict those patients who are likely to respond to radiotherapy.

Despite improvements in cancer management over the past 25 years, unrelieved symptoms continue to be reported. Little is known about how patients' problems and concerns are communicated to professionals during oncology treatment. This research investigates communication between cancer patients and clinicians in hospital outpatient clinics. Data were collected by non-participant observation and audio recording of consultations. Analyses were by qualitative content analysis and conversation analysis. An Objectives, Strategies and Tactics model was applied to organise the findings. 74 consultations between cancer patients and 15 doctors were observed and audio recorded. Pain talk is defined and identified as a substantial topic, occurring in 39/74 consultations. Doctor-initiated questions are the predominant discourse feature occupying over two-fifths of pain talk sequences. Their questions are prominent not only in initiating discussions but also in directing further talk. In other words, clinicians' questions control both the content and order of talk within pain talk sequences ( eg, over three-quarters of doctor-initiated questions are in a closed form which focus narrowly on limited physical aspects of patients' pain). It is argued that this limited information exchange alongside other communication tactics, is used to identify the 'right kind' of pain which may benefit from cancer therapy and to truncate talk of problems perceived to be outside of this specialist remit.