<p>Compared to people who are White and have high socioeconomic status (SES), those who are Black and have low SES are more likely to receive suboptimal pain care. One potential contributor to these disparities is biased provider decision-making—there is compelling evidence that providers are influenced by patient race and SES when making pain treatment decisions. According to the dual process model, people are more likely to be influenced by demographic stereotypes, including implicit beliefs, when they are under high cognitive load (i.e., mental workload). One stereotype belief relevant to pain care is that Black and low SES people are more pain tolerant. Aligned with the dual process model, providers who are under high cognitive load and have strong implicit beliefs that Black and low SES people are more pain tolerant may be particularly likely to recommend fewer pain treatments to them. To test this hypothesis, I recruited physician residents and fellows (n=120) to make pain treatment decisions for 12 computer-simulated patients with back pain that varied by race (Black/White) and SES (low/high). Half of the providers were randomized to the high cognitive load group in which they were interrupted during the decision task to make conversions involving hypertension medications for another patient. Remaining providers completed the task without being interrupted. Providers’ implicit beliefs about race and SES differences in pain tolerance were measured with two separate Implicit Association Tests (IATs). Multilevel modeling indicated that providers recommended stronger medications to low than high SES patients (OR=.68, p=.03). There was also a significant interaction between patient SES and cognitive load (OR=-.56, p=.05) and a trending interaction between patient race and cognitive load (OR=1.7, p=.07). Under low cognitive load, providers recommended more pain treatments to high SES (vs. low SES) and Black (vs. White) patients, but under high cognitive load, providers recommended more pain treatments to low SES (vs. high SES) patients and equivalent treatment to Black and White patients. There were no three-way interactions between patient demographics (race or SES), cognitive load, and providers’ implicit beliefs (race-pain or SES-pain IAT scores). However, there was a trending interaction between patient race and race-pain IAT scores (OR=2.56, p=.09). Providers with stronger implicit beliefs that White people are pain sensitive and Black people are pain tolerant recommended more pain treatments to White patients and fewer pain treatments to Black patients. Lastly, there was a trending effect that providers with stronger implicit beliefs that high SES people are pain sensitive and low SES people are pain tolerant recommended stronger medications in general (OR=13.03, p=.07). Results support that provider cognitive load is clinically relevant and impacts clinical decision-making for chronic pain for racially and socioeconomically diverse patients. Future studies are needed to further understand the impact of cognitive load on providers’ pain care decisions, which may inform evidence-based interventions to improve pain care and reduce disparities.</p> <p>  </p>

Acute and chronic pain conditions cause significant patient distress, interference with daily activities, and increased health care costs. It is important to evaluate analgesic interventions to improve pain relief, function, quality of life, and also to prevent persisting pain after surgery. This thesis is a combination of studies evaluating analgesic interventions in the setting of acute surgical pain; prevention of persistent post-surgical pain; and chronic low back pain. In part 1, we report our comparison of morphine and hydromorphone in 402 ambulatory surgery patients, for their ability to achieve satisfactory analgesia with minimal emesis using a design of multicentre randomized controlled trial. We observed no differences in their analgesic potential and common side effects and note that appearance of side effects is likely to be idiosyncratic. In part 2, we report our 2×2 factorial feasibility trial to prevent persistent post-surgical pain in patients having elective video-assisted thoracic surgery lobectomies, comparing N-methyl-D-aspartate antagonists versus placebo, and intravenous steroids versus placebo. As our feasibility outcomes were not met, we suggest appropriate considerations for protocol changes before embarking on a definitive larger trial. In part 3, we report on our systematic review and meta-analysis assessing the effectiveness and safety of gabapentinoids (gabapentin and pregabalin) in adult patients with chronic low back pain. We observed that the existing evidence is small and there is minimal improvement in pain and other outcomes with potential for adverse events. We suggest that the use of gabapentinoids for chronic low back pain merits caution and there is need for large high-quality trials. / Thesis / Doctor of Philosophy (PhD) / It is important to evaluate analgesic interventions to decrease pain, improve function, and lessen health care costs. In a randomized controlled trial of day surgery patients, we demonstrate that there are no differences between morphine and hydromorphone in achieving pain relief and common side effects. To prevent persistent post-surgical pain in patients having elective video-assisted thoracic surgery lobectomies, we performed a 2×2 factorial, feasibility randomized controlled trial, to compare N-methyl-D-aspartate antagonists versus placebo, and intravenous steroids versus placebo. We observe that appropriate protocol changes must be made before embarking on a larger trial. Finally, we report our systematic review and meta-analysis on the use of gabapentinoids in adult patients with chronic low back pain and observe that the existing evidence is small and not supportive, and the use of gabapentinoids for chronic low back pain merits caution.

Bakgrund: Ländryggssmärta är den globalt ledande orsaken till levda år med funktionsnedsättning. Långvarig ländryggssmärta (LLRS) är ett komplext tillstånd där patienterna har ett behov av att bemötas utifrån ett biopsykosocialt perspektiv. Det finns kvalitativa studier som undersökt patienters upplevelser av att leva med LLRS men få som utforskat hur dessa patienter upplever bemötandet inom vården. Syfte: Att på två olika primärvårdsmottagningar i Sverige undersöka hur patienter i arbetsför ålder med LLRS upplevde att de i vårdmötet blivit bemötta av vårdpersonal när de sökt vård för sin LLRS. Metod: Kvalitativ intervjustudie med induktiv ansats. Tio informanter i arbetsför ålder intervjuades med en semistrukturerad intervjuguide. Intervjuerna transkriberades ordagrant och analyserades med tematisk semantisk analys. Resultat: Analysen resulterade i två huvudteman: Det personliga mötet och Vårdens premisser. Dessa kännetecknades av patienternas önskemål om att få berätta sin historia, få en förklaring, bli kliniskt undersökta och möta vårdpersonal som respekterar och bekräftar dem. Tidsbrist, en känsla av att vara i underläge samt önskan om ökad delaktighet, samarbete och planering var ytterligare upplevelser som belystes. Slutsats: Denna studie visar att vårdpersonalens bemötande påverkar patienterna i stor utsträckning vilket belyser vikten av ett gott bemötande i vårdmötet samt nödvändigheten av att arbeta personcentrerat och utifrån ett biopsykosocialt perspektiv. / Background: Low back pain is the globally leading cause of years lived with disability. Long-term low back pain (LLBP) is a complex condition where patients have a need of being treated from a biopsychosocial perspective. There are qualitative studies which examine patients' experiences of living with LLBP, but only a few exploring how these patients experience the treatment in healthcare. Purpose: To investigate at two different primary health care clinics in Sweden how patients of working age with LLBP experienced that they were treated in the healthcare meeting by the healthcare professional when seeking healthcare for their LLBP. Method: A qualitative interview study with inductive approach. Ten men and women of working age were interviewed using a semi-structured interview guide. The interviews were transcribed literally and analysed with thematic semantic analysis. Results: The analysis resulted in two main themes: ”The personal meeting” and “The premises of healthcare”. These were characterised by the patients' desire to be able to tell their story, get an explanation, be clinically examined, and meet healthcare professionals who respect and acknowledge them. Lack of time, a feeling of being at a disadvantage and the desire for increased participation, cooperation, and planning were additional experiences highlighted. Conclusion: This study shows that the treatment by healthcare professionals affects patients widely which highlights the importance of a good treatment in healthcare and the necessity of working person-centred and from a biopsychosocial perspective.

Bakgrund: Långvarig nacksmärta är vanligt och drabbar ca 50% av världens befolkning. I Sverige drabbas kvinnor oftare än män. Ospecifik långvarig nacksmärta saknar känt ursprung. Behandlingen går oftast ut på att dämpa symtom och utbilda patienten i smärtan. Att istället utgå från att öka måluppfyllelse är ovanligare. Syftet med examensarbetet var att undersöka hur tilltro till behandling, katastroftankar samt smärtstillande medicinering påverkade graden av måluppfyllelse hos kvinnor i arbetsför ålder med ospecifik långvarig nacksmärta efter en rehabiliteringsperiod. Även sambandet mellan tilltro till behandling och katastroftankar undersöktes.  Metod: Detta är en retrospektiv longitudinell studie och sekundäranalys av data från en RCT studie med data tillhörande 65 kvinnor. Tilltro till behandling, katastroftankar och medicinering mättes innan rehabiliteringsperioden och måluppfyllelse mättes efter.  Resultat: Mann-whitney U-test visade ingen skillnad i måluppfyllelse efter rehabilitering mellan de med hög respektive neutral grad av tilltro till behandling (p=0, 395), låg respektive neutral grad av katastroftankar (p=0,59).  Sperman´s Rho test fann inget samband mellan tilltro och katastroftankar (p=0,751). De som tog medicin regelbundet hade en signifikant högre grad av måluppfyllelse mot de som ej tog medicin regelbundet (p=0,025).   Slutsats: Studien ger inte stöd för att tilltro till behandling och katastroftankar påverkar graden av måluppfyllelse. Inget samband mellan katastroftankar och graden av tilltro till behandling tycks finnas. Resultatet bör tolkas i ljuset av att data saknades för de med låg tilltro respektive höga katastroftankar. Smärtmedicinering tycks ha en positiv påverkan på måluppfyllelse. Mer kunskap om hur/vilken medicinering som påverkar måluppfyllelse behövs.

Since the first so-called “medical marijuana” legislation was passed in California in 1996, a total of twenty states and the District of Columbia have passed laws permitting limited use of cannabis. Despite the changes in state laws, cannabis remains illegal for any purpose under federal law. Changes in state laws have coincided with a renewed interest in the substance for the treatment of a variety of conditions. There has been a significant increase in published data over the past twenty years examining the efficacy of cannabis as an appetite stimulant, antiemetic agent, and analgesic adjuvant. The purpose of this meta-analysis was to synthesize published data on cannabis use as an analgesic agent. Five studies meeting inclusion criteria were located through searches of online databases, review of reference lists, author correspondence, and review of clinical trials databases. Meta-analysis was conducted using fixed-effects modeling. The overall effect of mean reduction of pain intensity was -4.895 (Z-score) with an associated p value of 0.003. The combined standardized mean difference (SMD) was -0.362 (CI -0.507 to -0.217), indicating on average a moderate significant reduction in pain intensity for patients with chronic pain. As the legal status of the substance evolves, additional research is needed to establish evidence-based clinical recommendations regarding the use of medicinal cannabis in pain management.

Thesis (MOccTher)-- University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Malingering, the intentional simulation or exaggeration of symptoms for secondary gain, has a significant financial impact on disability insurance given its prevalence. Multidisciplinary professionals involved in disability determination therefore require a tool which would assist in the screening of suspected malingerers. AIM: The Credibility Assessment Tool (CAT), a tool which was developed as part of the Performance APGAR, was reviewed in terms of its validity and application to the screening of malingering. Research objectives included the review of face and content validity through a literature review and concept analysis, as well as the review of construct and concurrent validity by comparing the results with the operationalised malingering construct and available malingering protocols. The adapted Slick criteria as proposed by Aronoff, applicable to chronic pain, neurocognitive, neurological and psychiatric symptoms, was identified as the most suitable criterion standard for use of comparison. DESIGN: The research design was a descriptive analytical design, which was performed retrospectively with a report review from insurance referrals to the researcher. Informed consent was obtained from insurers who legally own the reports. A saturated sample of convenience of 184 cases with depression and pain as predominant symptoms were analysed. Recall bias were minimised through omission of personal identifiers and the use of a peer check of 20 random cases. Results in the peer check were suggestive of poor inter-rater reliability, rather than recall bias. METHOD: Cases were analysed according to the guidelines from the respective authors of the CAT and adapted Slick criteria, however this was further defined to ensure that the study could be replicated. RESULTS: Face validity was adequate in terms of purpose, item selection and association between consistency criteria, however require improvement in terms of standardised instruction and weighting of the scale. Content validity was rated as adequate to excellent, given that it supports criteria linked to the malingering construct. Construct validity was adequate as demonstrated by association between concepts obtained through concept analysis. Correlation between the CAT and adapted Slick was strong (r>0.5) however caution is expressed that this requires further research. CONCLUSION: Recommendations for further research included the review of content validity with subject experts, criterion and predictive valid through a case-control study of known-groups, as well as the reliability of the CAT, and the use of specialised ADL indices for malingering detection. Adaptation to the CAT was depicted in the proposed Consistency Assessment Tool. / AFRIKAANSE OPSOMMING: Malingering, die opsetlike nabootsing of oordrywing van simptome vir sekondêre gewin, het ‘n beduidende finansiële impak op ongeskiktheidsversekering as gevolg van die prevalensie daarvan. Multidissiplinêre professionele persone betrokke by ongeskiktheidsevaluasies het daarom ‘n meetinstrument nodig om moontlike malingeerders te identifiseer. DOEL: Die Credibility Assessment Tool (CAT), wat ontwikkel was as deel van die Performance APGAR, was ondersoek in terme van geldigheid en toepassing op malingering. Navorsingsdoelwitte het die ondersoek van voorkoms- en inhoudsgeldigheid deur ‘n literatuurstudie en konsep analise behels, sowel as konstruk- en korrelasie geldigheid deur die vergelyking van die resultate met beskikbare malingering protokolle en operasionele konstrukte. Die aangepaste Slick kriteria soos voorgestel deur Aronoff, wat toepaslik is op kroniese pyn, neurokognitiewe, neurologiese en psigiatriese simptome, was ge-identifiseer as die meeste gepaste kriterium standaard vir vergelyking. ONTWERP: Die studieontwerp was ‘n beskrywende analitiese studie wat retrospektief uitgevoer was deur ‘n ondersoek van verslae van versekeraars. Ingeligte toestemming was verkry van versekeraars wat die wetlike eienaars van die verslae is. ‘n Gerieflikheidsteekproef van 184 gevalle met depressie en pyn as hoof simptome was geanaliseer. Sydighede was verminder deur persoonlike inligting te verwyder en die gebruik van ‘n eweknie evaluasie van 20 ewekansige getrekte gevalle. Voorlopige resultate dui onbevredigende betroubaarheid aan, eerder as sydighede. METODE: Gevalle was ge-evalueer volgends die riglyne van die verskeie outeure van die CAT en aangepaste Slick kriteria, en was sodanig verder gedefinieer om te verseker dat die studie herhaal kan word. RESULTATE: Voorkomsgeldigheid was voldoende, maar verbetering is aanbeveel in terme van gestandardiseerde instruksie en skaal verdeling. Inhoudsgeldigheid was beduidend in vergelyking met die wetenskaplike literatuur en die geoperasionaliseerde konstrukte. Konstrukgeldigheid was bevestig deur die positiewe verhoudings tussen die aangepaste Slick en CAT kriteria. ‘n Sterk korrelasie was gevind tussen die aangepaste Slick en CAT, maar hierdie moet versigtig geinterpreteer word aangesien verdere navorsing verlang word. GEVOLGTREKKING: Aanbevelings vir verdere navorsing sluit in die ondersoek van die inhoudsgeldigheid met eksperte, kriterium- en voorspellingsgeldigheid, sowel as die betroubaarheid van die CAT en die gebruik van gespesialiseerde ADL indekse vir uitkenning van malingering. Aanpassing vir die CAT word ook voorgestel.

Temporomandibular disorders (TMD) are a family of prevalent chronic pain disorders affecting masticatory muscles and/or the temporomandibular joint. There is no unequivocally recognized peripheral aetiology for idiopathic TMD. The central nervous system (CNS) may initiate and/or maintain the pain in idiopathic TMD due to sustained or long-term nociceptive input that induces maladaptive brain plasticity, and/or to inherent personality-related factors that may reduce the brain's capacity to modulate nociceptive activity. The main aim of this thesis is to determine whether there are structural neural abnormalities in patients with TMD, and whether these abnormalities are related to TMD pain characteristics, or to neuroticism. The specific aims are to delineate in TMD: (1) gray matter (GM) brain abnormalities and the contribution of pain and neuroticism to abnormalities; (2) the contribution of abnormal brain GM aging in focal cortical regions associated with nociceptive processes; and (3) abnormalities in brain white matter and trigeminal nerve and the contribution of pain. In groups of 17 female patients with TMD and 17 age- and sex- matched controls, magnetic resonance imaging revealed that patients with TMD had: (1) thicker cortex in the somatosensory, ventrolateral prefrontal and frontal polar cortices than controls, (2) cortical thickness in motor and cognitive areas that was negatively related to pain intensity, orbitofrontal cortical thickness that was negatively correlated to pain unpleasantness, and thalamic GM volume correlated to TMD duration, (3) an abnormal relationship between neuroticism and orbitofrontal cortical thickness, (4) abnormal GM aging in nociceptive, modulatory and motor areas, (5) widespread abnormalities in white matter tracts in the brain related to sensory, motor and cognitive functions, (6) reduced trigeminal nerve integrity related to pain duration, and (7) abnormal connectivity in cognitive and modulatory brain regions. In sum, this thesis demonstrates for the first time abnormalities in both peripheral nerve and CNS in patients with TMD.

Temporomandibular disorders (TMD) are a family of prevalent chronic pain disorders affecting masticatory muscles and/or the temporomandibular joint. There is no unequivocally recognized peripheral aetiology for idiopathic TMD. The central nervous system (CNS) may initiate and/or maintain the pain in idiopathic TMD due to sustained or long-term nociceptive input that induces maladaptive brain plasticity, and/or to inherent personality-related factors that may reduce the brain's capacity to modulate nociceptive activity. The main aim of this thesis is to determine whether there are structural neural abnormalities in patients with TMD, and whether these abnormalities are related to TMD pain characteristics, or to neuroticism. The specific aims are to delineate in TMD: (1) gray matter (GM) brain abnormalities and the contribution of pain and neuroticism to abnormalities; (2) the contribution of abnormal brain GM aging in focal cortical regions associated with nociceptive processes; and (3) abnormalities in brain white matter and trigeminal nerve and the contribution of pain. In groups of 17 female patients with TMD and 17 age- and sex- matched controls, magnetic resonance imaging revealed that patients with TMD had: (1) thicker cortex in the somatosensory, ventrolateral prefrontal and frontal polar cortices than controls, (2) cortical thickness in motor and cognitive areas that was negatively related to pain intensity, orbitofrontal cortical thickness that was negatively correlated to pain unpleasantness, and thalamic GM volume correlated to TMD duration, (3) an abnormal relationship between neuroticism and orbitofrontal cortical thickness, (4) abnormal GM aging in nociceptive, modulatory and motor areas, (5) widespread abnormalities in white matter tracts in the brain related to sensory, motor and cognitive functions, (6) reduced trigeminal nerve integrity related to pain duration, and (7) abnormal connectivity in cognitive and modulatory brain regions. In sum, this thesis demonstrates for the first time abnormalities in both peripheral nerve and CNS in patients with TMD.

The overall aim of this thesis was to gain new knowledge of factors and interventions that improve work ability and return to work (RTW) among women on long-term sick leave from human service organizations (HSOs). The specific aims of the studies were: to evaluate the associations between the self-rated Work Ability Index (WAI) and Work Ability Score (WAS), and the relationship with prospective sick leave, symptoms, and health (Paper I); to investigate whether intervention with myofeedback training or intensive muscular strength training could decrease pain and increase work ability among women with neck pain (Paper II); to examine the associations between workplace rehabilitation and the combination of supportive conditions at work with work ability and RTW over time (Paper III); and to explore experiences, views, and strategies in the rehabilitation process for RTW (Paper IV). This thesis is based on a prospective cohort study (n=324) and a randomized controlled study (RCT) (n=60, participants with neck pain). Both quantitative and qualitative methods were used. The data collection consisted of questionnaires, laboratory-observed data, register-based data, and interviews. The results showed a very strong association between WAI and WAS, and results predicted future sick leave degree, health-related quality of life, vitality, neck pain, self-rated general health, self-rated mental health, behavioral stress, and current stress (Paper I). In the RCT (Paper II), individuals in the myofeedback intervention group increased their vitality and work ability over time and individuals in the intensive musculoskeletal strength training group increased their WAI, WAS, and mental health over time. WAI, WAS, and RTW increased over time among individuals provided with workplace rehabilitation and supportive conditions at work (Paper III) such as a sense of feeling welcome back at work, influence at work, possibilities for development, degree of freedom at work, meaning of work, quality of leadership, social support, sense of community, and work satisfaction. Women described (Paper IV) how they were striving to work and how they had different views, strategies, and approaches in the rehabilitation process for RTW. They expressed a desire to work, their goals for work, and their wishes for work. In the rehabilitation process for RTW they described their interaction with stakeholders as either controlling the interaction or struggling in the interaction. They described strategies to cope with RTW in terms of yo-yo (fluctuating) working: yo-yo working as a strategy or yo-yo working as a consequence. This thesis identifies factors of importance in improving work ability and RTW among women on long-term sick leave from HSOs. For women with neck pain, the intervention study showed feasibility of the intervention and demonstrated improved work ability and decreased pain (Paper II). The intensive muscular strength training program, which is easy for the individual to learn and perform at home, was associated with increased work ability. The results regarding rehabilitation highlight the importance of integrating workplace rehabilitation with supportive conditions at work to increase work ability and improve RTW (Paper III). Women expressed that they were striving to work and that they wanted to work (Paper IV). These women were “going in and out” of work participation (yo-yo working) as a way to handle the rehabilitation process. For assessing the status and progress of work ability among women on long-term sick leave, the single-question WAS may be used as a compliment to the full WAI as a simple indicator (Paper I). / <p>Akademisk avhandling som för avläggande av medicine doktorsexamen vid Sahlgrenska akademin, Göteborgs universitet, kommer att offentligen försvaras i hörsal Hamberger, Medicinaregatan 16 A, Göteborg, måndagen den 6 oktober 2014, klockan 09.00</p>

At present, there are few clinically effective pain therapies available to treat chronic pain. One reason is due to a lack of understanding about how pain emerges in the brain. Excitingly, an emerging body of work suggests that the perfusion imaging technique, arterial spin labelling (ASL), is particularly well-suited to investigate this issue. The primary aim of this thesis is to develop and optimise a quantitative perfusion imaging approach to investigate the neural correlates of both experimental and pathological tonic pain. In Chapter 2, we explore different methods of inducing ongoing pain in healthy subjects. Results from this study show that mechanically induced pain is well suited for use in ASL FMRI experiments. In Chapter 3, we compare currently available ASL FMRI approaches for investigating tonic states, using a range of sensory paradigms. Results from these experiments support the use of an optimised version of Continuous ASL (CASL) FMRI to obtain whole-brain perfusion. Additionally, we discuss our decision to proceed with the newly acquired pseudo-continuous ASL (pCASL); a novel ASL technique that benefits from maximal signal-to-noise (SNR) across a whole-brain volume. In Chapter 4 we implement the pCASL FMRI approach to image the neural correlates of ongoing experimental pain. Results from the investigation of parametrically modulated ongoing mechanical pain show robust pain-related activation of key pain related regions that are monotonically active with an increase in stimulus intensity. Additionally, data from this experiment shows the presence of complex perfusion dynamics relative to pain worthy of further study. In Chapter 5, we optimised the pCASL sequence to obtain absolute perfusion changes across the whole-brain volume, using multi-inversion times, so that we could investigate the perfusion dynamics observed in Chapter 4. Results show that absolute perfusion changes during tonic pain are considerably less than for regions recruited during a non- pain task. Additionally, dynamic perfusion changes show complex stimulus responses across all active regions regardless of stimulus type. We conclude that while the technique is well suited to quantify absolute perfusion, the mechanisms underlying the dynamic changes in CBF (neuronal signal, neurovascular coupling) need further study. Finally, in Chapter 6, we implement the absolute perfusion approach developed in Chaper 5 to interrogate the neural correlates of the genetic pain disease, Erythromelalgia, and pleasurable relief. The results of this study show pain-related activation (and relief-induced reduction) of key pain-related regions. We conclude from these results that the ASL technique developed over the course of this thesis can be used to study a range of pain pathologies. Taken together, the results of this thesis document the development of a powerful perfusion imaging technique capable of quantifying absolute perfusion changes across a whole-brain volume. The data presented here from investigations of both experimental and pathological pain states supports the use of this technique in future tonic pain studies, as well as other neuroscience applications. We are confident that implementation of this imaging approach will provide integral insight into the mechanisms of ongoing pain states; and further the development of novel efficacious pain treatment options.