This cross-sectional study investigates the plasma inflammatory profile of chronic widespread pain CWP) patients compared to healthy controls CON). Rather than analyzing a relatively few substances at a time, we used a new multiplex proximity extension assay PEA) panel that enabled the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines. Seventeen women with CWP and 21 female CON participated and a venous blood sample was drawn from all subjects. Pain intensity and pain thresholds for pressure, heat, and cold were registered. A PEA panel 92 proteins) was used to analyze the blood samples. Multivariate data analysis by projection was used in the statistical analyses. Eleven proteins significantly differentiated the CON and CWP subjects R-2=0.58, Q(2)=0.37, analysis of variance of cross-validated predictive residuals P=0.006). It was not possible to significantly regress pain thresholds within each group CON or CWP). Positive significant correlations existed between several proteins and pain intensities in CWP, but the model reliability of the regression was poor. CWP was associated with systemic low-grade inflammation. Larger studies are needed to confirm the results and to investigate which alterations are condition-specific and which are common across chronic pain conditions. The presence of inflammation could promote the spreading of pain, a hallmark sign of CWP. As it has been suggested that prevalent comorbidities to pain (e.g., depression and anxiety, poor sleep, and tiredness) also are associated with inflammation, it will be important to determine whether inflammation may be a common mediator. ; Funding Agencies|Uppsala Berzelii Technology Center for Neurodiagnostics; Swedish Governmental Agency for Innovation Systems (VINNOVA); Swedish Research Council [P29797-1, K2015-99x-21874-05-4]; County Council of Ostergotland [LIO-35923, SC-2013-00395-36]; AFA Insurance [140341]
Chronic pain among elderly people has long been a well-known problem, in terms of both societal costs and the quality of life of affected individuals. To estimate the magnitude of the problems associated with chronic pain in an elderly population, data on both costs and quality of life were gathered. A postal questionnaire was sent out to a stratified sample of 10 000 inhabitants 65 years and older in Linköping and Norrköping. The survey included questions on demographics, habits, and life situation, and different kinds of questions and instruments related to well-being (e.g., quality-of-life and pain-specific questions). In the questionnaire respondents were asked whether they were receiving any help—informal care—from a relative. If they answered yes, they were asked for permission to contact the informal caregiver and to provide contact details. The amount of informal care provided by relatives to persons with chronic pain was investigated by use of a questionnaire directed to the caregiving relatives, containing questions about time spent providing informal care. Data on costs were collected from registers of consumption of health care, drugs, and municipal services. The results of the study showed a very clear association between existence and severity of chronic pain and societal costs. The study population was subdivided into three groups with respect to having chronic pain or not, and a pain intensity during the last week of 0–4 (mild), 5–7 (moderate), or 8–10 (severe) on a scale of 0–10. Taking all costs (health care, drugs, municipal services, and informal care) into account, persons in the severe chronic pain group consumed on average 72% more resources than persons in the moderate chronic pain group and 143% more than those in the no or mild chronic pain group. Differences were most pronounced concerning municipal services and informal care costs. Even more alarming are the results on the quality of life of persons in the different groups. On the EQ-5D index, the average value for persons in the no or mild chronic pain group was 0.82. For those in the moderate chronic pain group the average value was 0.64, and for those in the severe chronic pain group the average value was only 0.38. EQ-VAS resulted in less pronounced but still clearly significant differences. It is concluded that this study, reaching a rather large part of the target population, shows that existence and severity of chronic pain among people 65 years and older affects costs to society and the quality of life of affected individuals in a massive way. ; Kronisk smärta bland äldre är sedan länge ett välkänt problem, både i termer av samhälleliga kostnader och i termer av nedsatt livskvalitet hos drabbade individer. I syfte att uppskatta omfattningen av problemen med kronisk smärta i den äldre befolkningen insamlades data avseende såväl kostnader som livskvalitet. Ett frågeformulär sändes med post ut till ett stratifierat urval om 10 000 invånare 65 år och äldre i Linköpings och Norrköpings kommuner. Frågeformuläret innehöll frågor om demografi, levnadsvanor, livssituation samt olika frågor och instrument relaterade till personernas mående (t.ex. livskvalitet och smärtspecifika frågor). I frågeformuläret tillfrågades respondenterna om huruvida de mottog någon hjälp, informell vård, från någon närstående. Om så var fallet tillfrågades respondenten om tillstånd att kontakta dennes informella vårdgivare, samt kontaktuppgifter. Mängden informell vård tillhandahållen av närstående undersöktes med hjälp av ett frågeformulär innehållande frågor om tid som använts till informella vårdinsatser. Uppgifter om kostnader inhämtades från register avseende konsumtion av sjukvård, läkemedel och kommunala insatser. Studiens resultat visade på ett mycket tydligt samband mellan å ena sidan förekomst och grad av kronisk smärta och å andra sidan samhälleliga kostnader. Studiepopulationen delades in i tre grupper med avseende på kronisk smärta eller inte, och smärtintensitet på en 10-gradig skala under den senaste veckan (0–4 = lindrig, 5–7 = måttlig, 8–10 = svår). Med hänsyn tagen till alla kostnader (sjukvård, läkemedel, kommunal service och informell vård) konsumerade personerna med svår kronisk smärta i snitt 72% mer resurser än personerna med måttlig kronisk smärta, och 143% mer än personer med ingen eller lindrig kronisk smärta. Skillnaderna var tydligast avseende kommunala insatser och informell vård. Ännu mer uppseendeväckande är resultaten gällande livskvalitet för personer i de olika grupperna. Genomsnittligt indexvärde utifrån EQ-5D var för personer med ingen eller lindrig kronisk smärta 0.82. För personer med måttlig kronisk smärta var motsvarande värde 0.64, och för personer med svår kronisk smärta var värdet 0.38. EQ-VAS resulterade i mindre uttalade men tydligt signifikanta skillnader. Denna studie, som når en relativt stor andel av målpopulationen, visar att förekomst och intensitet av kronisk smärta bland personer 65 år och äldre påverkar samhälleliga kostnader och drabbade personers livskvalitet mycket tydligt.
Objectives: Multimodal rehabilitation programs (MMRPs) have been shown to be both cost-effective and an effective method for managing chronic pain in specialist care. However, while the vast majority of patients are treated in primary healthcare, MMRPs are rarely practiced in these settings. Limited time and resources for everyday activities alongside the complexity of chronic pain makes the management of chronic pain challenging in primary healthcare and the focus is on unimodal treatment. In order to increase the use of MMRPs incentives such as cost savings and improved health status in the patient group are needed. The aim of this study was to evaluate the cost-effectiveness of MMRPs for patients with chronic pain in primary healthcare in two Swedish regions. The aim of this study was to evaluate the cost-effectiveness of MMRPs at one-year follow-up in comparison with care as usual for patients with chronic pain in primary healthcare in two Swedish regions. Methods: A cost-utility analysis was performed alongside a prospective cohort study comparing the MMRP with the alternative of continuing with care as usual. The health-related quality of life (HRQoL), using EQ5D, and working situation of 234 participants were assessed at baseline and one-year follow-up. The primary outcome was cost per quality-adjusted life year (QALY) gained while the secondary outcome was sickness absence. An extrapolation of costs was performed based on previous long-term studies in order to evaluate the effects of the MMRP over a five-year time period. Results: The mean (SD) EQ5D index, which measures HRQoL, increased significantly (p<0.001) from 0.34 (0.32) to 0.44 (0.32) at one-year follow-up. Sickness absence decreased by 15%. The cost-utility analysis showed a cost per QALY gained of 18 704 € at one-year follow-up. Conclusions: The results indicate that the MMRP significantly improves the HRQoL of the participants and is a cost-effective treatment for patients with chronic pain in primary healthcare when a newly suggested cost-effectiveness threshold of 19 734 € is implemented. The extrapolation indicates that considerable cost savings in terms of reduced loss of production and gained QALYs may be generated if the effects of the MMRP are maintained beyond one-year follow-up. The study demonstrates potential benefits of MMRPs in primary healthcare for both the patient with chronic pain and the society as a whole. The cost-effectiveness of MMRPs in primary healthcare has scarcely been studied and further long-term studies are needed in these settings.
Objective: Neuropathic pain and fibromyalgia are two common and poorly understood chronic pain conditions that lack satisfactory treatments, cause substantial suffering and societal costs. Today, there are no biological markers on which to base chronic pain diagnoses, treatment choices or to understand the pathophysiology of pain for the individual patient. This study aimed to investigate cerebrospinal fluid (CSF) protein profiles potentially associated with fibromyalgia and neuropathic pain. Methods: CSF samples were collected from 25 patients with neuropathic pain (two independent sets, n=14 patients for discovery, and n=11 for verification), 40 patients with fibromyalgia and 134 controls without neurological disease from two different populations. CSF protein profiling of 55 proteins was performed using antibody suspension bead array technology. Results: We found increased levels of apolipoprotein C1 (APOC1) in CSF of neuropathic pain patients compared to controls and there was a trend for increased levels also in fibromyalgia patients. In addition, levels of ectonucleotide pyrophosphatase family member 2 (ENPP2, also referred to as autotaxin) were increased in the CSF of fibromyalgia patients compared to all other groups including patients with neuropathic pain. Conclusion: The increased levels of APOC1 and ENPP2 found in neuropathic pain and fibromyalgia patients may shed light on the underlying mechanisms of these conditions. Further investigation is required to elucidate their role in maintaining pain and other main symptoms of these disorders. ; Funding Agencies|Swedish Governmental Agency for Innovation SystemsVinnova; Swedish Research Council (Vetenskapsradet)Swedish Research Council; Uppsala University; KTH Center for Applied Precision Medicine (KCAP); Marie-Curie fellowship from the INSENS/FP7-PEOPLE-2013European Union (EU) [607616]; NEURO Sweden; AFA Insurance; ALF Grants, Region Ostergotland
The translocator protein (TSPO) is upregulated during glia activation in chronic pain patients. TSPO constitutes the rate-limiting step in neurosteroid synthesis, thus modulating synaptic transmission. Related serotonergic mechanisms influence if pro- or anti-nociceptive neurosteroids are produced. This study investigated the effects of a functional genetic polymorphism regulating the binding affinity to the TSPO, thus affecting symptom severity and cerebral pain processing in fibromyalgia patients. Gene-to-gene interactions with a functional polymorphism of the serotonin transporter gene were assessed. Fibromyalgia patients (n = 126) were genotyped regarding the polymorphisms of the TSPO (rs6971) and the serotonin transporter (5-HTTLPR/rs25531). Functional magnetic resonance imaging (n = 24) was used to study brain activation during individually calibrated pressure pain. Compared to mixed/low TSPO affinity binders, the high TSPO affinity binders rated more severe pain (p = 0.016) and fibromyalgia symptoms (p = 0.02). A significant interaction was found between the TSPO and the serotonin transporter polymorphisms regarding pain severity (p amp;lt; 0.0001). Functional connectivity analyses revealed that the TSPO high affinity binding group had more pronounced pain-evoked functional connectivity in the right frontoparietal network, between the dorsolateral prefrontal area and the parietal cortex. In conclusion, fibromyalgia patients with the TSPO high affinity binding genotype reported a higher pain intensity and more severe fibromyalgia symptoms compared to mixed/low affinity binders, and this was modulated by interaction with the serotonin transporter gene. To our knowledge this is the first evidence of functional genetic polymorphisms affecting pain severity in FM and our findings are in line with proposed glia-related mechanisms. Furthermore, the functional magnetic resonance findings indicated an effect of translocator protein on the affective-motivational components of pain perception. (C) 2016 The Authors. Published by Elsevier Inc. ; Funding Agencies|Swedish Rheumatism Association; Stockholm County Council; Swedish Foundation for Strategic Research [2012-0179]; Swedish Research Council [K2013-52X-22199-01-3, K2015-99x-21874-05-4, 2011-4807, K2009-52P-20943-03-2]; AFA insurance; Karolinska Institutet Foundation; Karolinska Institutet; European Union [602919]
