| 1. |
- Gerdle, Björn, et al.
(författare)
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Chronic Widespread Pain : Increased Glutamate and Lactate Concentrations in the Trapezius Muscle and Plasma
- 2014
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Ingår i: The Clinical Journal of Pain. - : Lippincott Williams & Wilkins. - 0749-8047 .- 1536-5409. ; 30:5, s. 409-420
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND:: Chronic widespread pain (CWP), including fibromyalgia syndrome (FM), is associated with prominent negative consequences. CWP has been associated with alterations in the central processing of nociception. Whereas some researchers consider CWP/FM as a central hyperexcitability pain condition, others suggest that the central alterations are maintained by peripheral nociceptive input. Microdialysis can be used in vivo to study muscle alterations in chronic myalgia. AIM:: The aim of the study was to investigate the plasma and interstitial concentrations of metabolites and algesics in the trapezius muscle of women with CWP and in pain-free women (CON).MATERIALS AND METHODS:: Seventeen women with CWP and 24 CON went through a clinical examination and completed a questionnaire; the pressure pain thresholds in the upper and lower extremities were registered. Microdialysis was conducted in the trapezius muscle, and a blood sample was drawn. Muscle blood flow, interstitial muscle concentrations, and plasma concentrations of lactate, pyruvate, glutamate, glucose, and glycerol (not in the plasma) were determined.RESULTS:: CWP patients had significantly increased interstitial muscle (P=0.02 to 0.001) and plasma (P=0.026 to 0.017) concentrations of lactate and glutamate. No significant differences existed in blood flow between CWP and CON. The interstitial concentrations-but not the plasma levels-of glutamate and lactate correlated significantly with aspects of pain such as pressure pain thresholds of the trapezius (R=0.22) and tibialis anterior (R=0.18) and the mean pain intensity (R=0.10) in CWP but not in CON.CONCLUSIONS:: The present study supports the suggestion that aspects of pain and central alterations in CWP/FM are influenced by peripheral tissue alterations.
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| 2. |
- Gerdle, Björn, et al.
(författare)
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Signs of ongoing inflammation in female patients with chronic widespread pain A multivariate, explorative, cross-sectional study of blood samples
- 2017
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Ingår i: Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0025-7974 .- 1536-5964. ; 96:9
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Ghafouri, Nazdar, et al.
(författare)
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Effects of two different specific neck exercise interventions on palmitoylethanolamide and stearoylethanolamide concentrations in the interstitium of the trapezius muscle in women with chronic neck shoulder pain
- 2014
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Ingår i: Pain medicine (Malden, Mass.). - : Oxford University Press (OUP). - 1526-2375 .- 1526-4637. ; 15:8, s. 1379-1389
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. Chronic neck/shoulder pain (CNSP) is one of the most common pain conditions. The understanding of mechanisms, including the peripheral balance between nociceptive and antinociceptive processes, is incomplete. N-acylethanolamines (NAEs) are a class of endogenous compounds that regulate inflammation and pain. The aim of this study was to investigate the levels of two NAEs: the peroxisome proliferator-activated receptor type-a ligand palmitoylethanolamide (PEA) and stearoylethanolamide (SEA) in the muscle interstitium of the trapezius muscle in women with CNSP randomized to two different neck specific training programs and in a healthy pain-free control group (CON). Materials and Methods. Fifty-seven women with CNSP were randomized to strength + stretch or stretch alone exercise programs. Twenty-nine subjects underwent microdialysis procedure before and after 4-6 months of exercise. Twenty-four CON subjects underwent microdialysis procedure before and after 4-6 months without any intervention in between. Microdialysate samples were collected from the trapezius muscle and analyzed by mass spectrometry for PEA and SEA levels. Results. PEA and SEA levels were significantly higher in CNSP patients compared with CON. PEA was significantly higher in CNSP than in CON after both training programs. SEA was significantly higher in CNSP than in CON after stretch alone but not after strength + stretch training. A significant positive correlation was found between changes in pain intensity and in SEA levels in the strength + stretch group, but not in the stretch alone group. Conclusion. Our results indicate that exercise interventions differentially affect the levels of the bioactive lipids PEA and SEA in the interstitium of the trapezius muscle in women with CNSP.
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| 4. |
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| 5. |
- Ghafouri, Nazdar, et al.
(författare)
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High Levels of N-Palmitoylethanolamide and N-Stearoylethanolamide in Microdialysate Samples from Myalgic Trapezius Muscle in Women
- 2011
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Ingår i: PLOS ONE. - San Fransisco : Public Library of Science. - 1932-6203. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: N-acylethanolamines (NAEs) are endogenous compounds that regulate inflammation and pain. These include the cannabinoid ligand anandamide (AEA) and the peroxisome proliferator-activated receptor-a ligand palmitoylethanolamide (PEA). Little is known as to the levels of NAEs in pain states in human, particularly in the skeletal muscle. The aim of this study was to investigate the levels of these lipid mediators in muscle dialysate from women with chronic neck-/shoulder pain compared to healthy controls. Methods: Eleven women with chronic neck-/shoulder pain and eleven healthy women participated in this study. All participants went through microdialysis procedures in the trapezius muscle. Muscle dialysate samples were collected during four hours and analysed by nano liquid chromatography tandem mass spectrometry (nLC-MS/MS). Results: We were able to detect AEA, PEA, N-stearoylethanolamine (SEA) and 2-arachidonoylglycerol (2-AG) in a single chromatographic run. Of the NAEs studied, PEA and SEA were clearly detectable in the muscle microdialysate samples. The muscle dialysate levels of PEA and SEA were significantly higher in myalgic subjects compared to healthy controls. Conclusion: This study demonstrates that microdialysis in combination with mass spectrometry can be used for analysing NAEs in human muscle tissue regularly over time. Furthermore the significant group differences in the concentration of PEA and SEA in this study might fill an important gap in our knowledge of mechanisms in chronic myalgia in humans. In the long run this expanded understanding of nociceptive and anitinociceptive processes in the muscle may provide a base for ameliorating treatment and rehabilitation of pain.
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| 6. |
- Ghafouri, Nazdar, 1980-, et al.
(författare)
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Mental health in genocide: Balancing between posttraumatic distress and growth among displaced Yazidi mothers
- 2024
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Ingår i: Journal of Mental Health. - : TAYLOR & FRANCIS INC. - 0963-8237 .- 1360-0567.
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Tidskriftsartikel (refereegranskat)abstract
- Background. The Islamic State of Iraq and Syria (ISIS) committed genocide of the Yazidis in Sinjar 2014, resulting in dispersion and enslavement. Research shows severe mental health problems, such as posttraumatic stress disorder (PTSD) among survivors, but less is known about their resources and strengths, conceptualized as posttraumatic growth (PTG). Aims. are to examine the balance between symptoms and strengths among Yazidi women caring for their infants by identifying groups differing in PTSD and PTG, and analyze how demographic, obstetric, and infant-related factors associate with the groups. Method. Participants were 283 Yazidi mothers with their 1-18-month-old infants displaced in Kurdish Region of North Iraq. PTSD symptoms were measured by Harvard Trauma Questionnaire and PTG by the Posttraumatic Growth Inventory. Results. identified four groups: "Severe symptoms and low growth" (39%), "Low symptoms and moderate growth" (38%), "Moderate symptoms and very high growth" (13%), and "Moderate symptoms and low growth" (10%). Low education, economic difficulties and obstetric problems related to the "Severe symptoms and low growth" group, whereas newborn and infant health problems did not have an impact. Conclusion. Effective help for genocide survivors should both alleviate suffering and encourage resources through tools of recreating a sense of cultural security and pride.
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| 7. |
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| 8. |
- Ghafouri, Nazdar, et al.
(författare)
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Palmitoylethanolamide and stearoylethanolamide levels in the interstitium of the trapezius muscle of women with chronic widespread pain and chronic neck-shoulder pain correlate with pain intensity and sensitivity
- 2013
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Ingår i: Pain. - : Elsevier. - 0304-3959 .- 1872-6623. ; 154:9, s. 1649-1658
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Tidskriftsartikel (refereegranskat)abstract
- Chronic widespread pain (CWP) is a complex condition characterized by central hyperexcitability and altered descending control of nociception. However, nociceptive input from deep tissues is suggested to be an important drive. N-Acylethanolamines (NAEs) are endogenous lipid mediators involved in regulation of inflammation and pain. Previously we have reported elevated levels of the 2 NAEs, the peroxisome proliferator-activated receptor type-alpha ligand N-palmitoylethanolamine (PEA) and N-stearoylethanolamine (SEA) in chronic neck/shoulder pain (CNSP). In the present study, the levels of PEA and SEA in women with CWP (n = 18), CNSP (n = 34) and healthy controls (CON, n = 24) were investigated. All subjects went through clinical examination, pressure pain threshold measurements and induction of experimental pain in the tibialis anterior muscle. Microdialysis dialysate of the trapezius was collected before and after subjects performed a repetitive low-force exercise and analyzed by mass spectrometry. The levels of PEA and SEA in CNSP were significantly higher post exercise compared with CWP, and both pre and post exercise compared with CON. Levels of both NAEs decreased significantly pre to post exercise in CWP. Intercorrelations existed between aspects of pain intensity and sensitivity and the level of the 2 NAEs in CWP and CNSP. This is the first study demonstrating that CNSP and CWP differ in levels of NAEs in response to a low-force exercise which induces pain. Increases in pain intensity as a consequence of low-force exercise were associated with low levels of PEA and SEA in CNSP and CWP. These results indicate that PEA and SEA have antinociceptive roles in humans.
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| 9. |
- Håkansson, Irene, et al.
(författare)
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Oxylipins in cerebrospinal fluid in clinically isolated syndrome and relapsing remitting multiple sclerosis
- 2018
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Ingår i: Prostaglandins & other lipid mediators. - : Elsevier. - 1098-8823 .- 2212-196X. ; 138, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- Although oxylipins are involved in inflammation, data on these lipid mediators in multiple sclerosis are sparse. In this study, a panel of oxylipins were analysed swith liquid chromatography tandem mass spectrometry in cerebrospinal fluid (CSF) from 41 treatment naive patients with clinically isolated syndrome (CIS) or relapsing remitting MS (RRMS) and 22 healthy controls. CSF levels of 9-hydroxyoctadecadienoic acid (9-HODE) and 13-hydroxyoctadecadienoic acid (13-HODE) were significantly higher in patients than in healthy controls (9-HODE median 380 nM (interquartile range 330-450 nM) in patients and 290 nM (interquartile range 250-340 nM) in controls, 13-HODE median 930 nM (interquartile range 810-1080 nM) in patients and 690 nM (interquartile range 570-760 nM) in controls, p < 0.001 in Mann-Whitney U tests). 9-HODE and 13-HODE performed well for separation of patients and healthy controls (AUC 0.85 and 0.88, respectively, in ROC curve analysis). However, baseline CSF levels of the oxylipins did not differ between patients with signs of disease activity during one, two and four years of follow-up and patients without. In conclusion, this study indicates that 9-HODE and 13-HODE levels are increased in CSF from CIS and RRMS patients compared with healthy controls, but does not support 9-HODE or 13-HODE as prognostic biomarkers of disease activity in patients during follow-up.
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| 10. |
- Karlsson, Linn, et al.
(författare)
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Intramuscular pain modulatory substances before and after exercise in women with chronic neck pain
- 2015
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Ingår i: European Journal of Pain. - : WILEY-BLACKWELL. - 1090-3801 .- 1532-2149. ; 19:8, s. 1075-1085
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn peripheral tissue, several substances influence pain and pain modulation. Exercise has been found to decrease pain and improve function for chronic pain conditions, but how and why exercise produces beneficial effects remains unclear. This study investigates whether aspects of pain and concentrations of substances with algesic, analgesic and metabolic functions differ between women with chronic neck shoulder pain (CNSP) and healthy women (CON) and whether changes are found after an exercise intervention for CNSP. MethodsForty-one women with CNSP and 24 CON subjects were included. The participants attended two microdialysis sessions with 4-6 months between the experiments. During this period, the CNSP subjects underwent an exercise intervention. Expression levels of substance P, beta-endorphin, cortisol, glutamate, lactate and pyruvate as well as pain intensity and pressure pain thresholds were analysed. ResultsAt baseline, higher concentrations of glutamate and beta-endorphin and lower concentrations of cortisol in CNSP than CON were found. After exercise, decreased levels of substance P and possibly of glutamate, increased levels of beta-endorphin and cortisol as well as decreased pain intensity and increased pain pressure thresholds were found for CNSP. ConclusionsThe findings at baseline indicated algesic and analgesic alterations in the painful trapezius muscles. The findings for CNSP after the exercise intervention, with changes in peripheral substances and decreased pain intensity and sensitivity, could reflect a long-term physiological effect of the exercise.
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| 11. |
- Olausson, Patrik, et al.
(författare)
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Identification of Proteins from Interstitium of Trapezius Muscle in Women with Chronic Myalgia Using Microdialysis in Combination with Proteomics
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Microdialysis (MD) of the trapezius muscle has been an attractive technique to investigating small molecules and metabolites in chronic musculoskeletal pain in human. Large biomolecules such as proteins also cross the dialysis membrane of the catheters. In this study we have applied in vivo MD in combination with two dimensional gel electrophoresis (2-DE) and mass spectrometry to identify proteins in the extracellular fluid of the trapezius muscle. Materials and Methods: Dialysate from women with chronic trapezius myalgia (TM; n = 37), women with chronic wide spread pain (CWP; n = 18) and healthy controls (CON; n = 22) was collected from the trapezius muscle using a catheter with a cut-off point of 100 kDa. Proteins were separated by two-dimensional gel electrophoresis and visualized by silver staining. Detected proteins were identified by nano liquid chromatography in combination with tandem mass spectrometry. Results: Ninety-seven protein spots were identified from the interstitial fluid of the trapezius muscle; 48 proteins in TM and 30 proteins in CWP had concentrations at least two-fold higher or lower than in CON. The identified proteins pertain to several functional classes, e.g., proteins involved in inflammatory responses. Several of the identified proteins are known to be involved in processes of pain such as: creatine kinase, nerve growth factor, carbonic anhydrase, myoglobin, fatty acid binding protein and actin aortic smooth muscle. Conclusions: In this study, by using in vivo microdialysis in combination with proteomics a large number of proteins in muscle interstitium have been identified. Several of the identified proteins were at least two-fold higher or lower in chronic pain patients. The applied techniques open up for the possibility of investigating protein changes associated with nociceptive processes of chronic myalgia. © 2012 Olausson et al.
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| 12. |
- Olausson, Patrik, et al.
(författare)
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Protein alterations in women with chronic widespread pain : An explorative proteomic study of the trapezius muscle
- 2015
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Ingår i: Scientific Reports. - : Nature Publishing Group: Open Access Journals - Option C / Nature Publishing Group. - 2045-2322. ; 5:11894
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Tidskriftsartikel (refereegranskat)abstract
- Chronic widespread pain (CWP) has a high prevalence in the population and is associated with prominent negative individual and societal consequences. There is no clear consensus concerning the etiology behind CWP although alterations in the central processing of nociception maintained by peripheral nociceptive input has been suggested. Here, we use proteomics to study protein changes in trapezius muscle from 18 female patients diagnosed with CWP compared to 19 healthy female subjects. The 2-dimensional gel electrophoresis (2-DE) in combination with multivariate statistical analyses revealed 17 proteins to be differently expressed between the two groups. Proteins were identified by mass spectrometry. Many of the proteins are important enzymes in metabolic pathways like the glycolysis and gluconeogenesis. Other proteins are associated with muscle damage, muscle recovery, stress and inflammation. The altered expressed levels of these proteins suggest abnormalities and metabolic changes in the myalgic trapezius muscle in CWP. Taken together, this study gives further support that peripheral factors may be of importance in maintaining CWP.
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| 13. |
- Olausson, Patrik, et al.
(författare)
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Relative recovery over time – an in vivo microdialysisstudy of human skeletal muscle
- 2013
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa Healthcare. - 0036-5513 .- 1502-7686. ; 73:1, s. 10-16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The microdialysis technique is a method for sampling endogenous molecules from the interstitial compartments of varying tissues and relies on diffusion of molecules between the tissue and a perfusate via a membrane. Such samples do not allow determination of the true interstitial concentration but only a certain percentage. This gives rise to one of the most crucial parameter that needs to be considered for a dependable microdialysis; the relative recovery. Relative recovery states the efficiency of which an analyte is extracted from its external medium. Aim. To investigate the relative recovery of small molecules (< 20 kDa) such as lactate, fluid recovery and the reproducibility of the relative recovery at group and individual level of the microdialysis technique applied in muscle.MATERIALS AND METHODS:Using in vivo microdialysis of the trapezius muscle of 65 women from two separate occasions 4-6 months apart. Relative recovery of small molecules was measured from samples collected every 20 min during a period of 220 min.RESULTS:Good reproducibility at group level of catheters with cut-offs 100 and 20kDa were found. Furthermore, there was a high and steady relative recovery with an overall good fluid recovery. Poor reproducibility was found at the individual level for both catheters.CONCLUSIONS:This study demonstrates that when using microdialysis in skeletal muscle relative recovery is stable over time and is not affected by low-force exercise. Although there is a good reproducibility at group level this is not the case at the individual level. Thus in vivo, the relative recovery should be determined for each test subject and at each test occasion.
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| 14. |
- Olausson, Patrik, et al.
(författare)
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Specific proteins of the trapezius muscle correlate with pain intensity and sensitivity - an explorative multivariate proteomic study of the trapezius muscle in women with chronic widespread pain
- 2016
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Ingår i: Journal of Pain Research. - : DOVE MEDICAL PRESS LTD. - 1178-7090. ; 9, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- Chronic widespread pain (CWP) including fibromyalgia syndrome (FMS) has a high prevalence and is associated with prominent negative consequences. CWP/FMS exhibits morphological and functional alterations in the central nervous system. The importance of peripheral factors for maintaining the central alterations are under debate. In this study, the proteins from biopsies of the trapezius muscle from 18 female CWP/FMS patients and 19 healthy female controls were analyzed. Pain intensity and pressure pain thresholds (PPT) over the trapezius muscles were registered. Twelve proteins representing five different groups of proteins were important regressors of pain intensity in CWP/FMS (R-2=0.99; P amp;lt; 0.001). In the regression of PPT in CWP/FMS, it was found that 16 proteins representing six groups of proteins were significant regressors (R-2=0.95, P amp;lt; 0.05). Many of the important proteins were stress and inflammation proteins, enzymes involved in metabolic pathways, and proteins associated with muscle damage, myopathies, and muscle recovery. The altered expression of these proteins may reflect both direct and indirect nociceptive/inflammatory processes as well as secondary changes. The relative importance of the identified proteins and central alterations in CWP need to be investigated in future research. Data from this and the previous study concerning the same cohorts give support to the suggestion that peripheral factors are of importance for maintaining pain aspects in CWP/FMS.
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| 15. |
- Sorensen, Line Bay, et al.
(författare)
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Investigation of biomarkers alterations after an acute tissue trauma in human trapezius muscle, using microdialysis
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Alterations in muscle milieu are suggested as important activity of peripheral drive in patients with chronic musculoskeletal pain (CMP). Microdialysis (MD) has been used in monitoring altered metabolic response pattern in muscles. However, the insertion of MD probe causes a local tissue trauma. Whether and how metabolites in trapezius muscle are affected by acute tissue trauma is unknown. Hence, this study investigated the metabolic response and nociceptive reaction of the tissue following MD probe insertion in patients with CMP and healthy individuals. Fifty-nine patients and forty pain-free volunteers were recruited. Pressure pain thresholds (PPTs) were obtained at the trapezius and tibialis muscles. Pain questionnaires determined the levels of pain related aspects. MD (20 kDa cut-off) was performed in the trapezius and samples were collected within 40 min. Interstitial concentration of the metabolites was analyzed by a two-way-mixed-ANOVA. The metabolic response pattern changed over time and alterations in the level of metabolites could be seen in both CMP and healthy controls. Pain questionnaires and pain intensities manifested clinical aspects of pain closely to what CMP patients describe. Analyzing metabolites due to acute tissue trauma by aid of MD may be a useful model to investigate altered metabolic response effect in CMP.
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| 16. |
- Stensson, Niclas, 1974-, et al.
(författare)
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Alterations of anti-inflammatory lipids in plasma from women with chronic widespread pain - a case control study
- 2017
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Ingår i: Lipids in Health and Disease. - : BIOMED CENTRAL LTD. - 1476-511X. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic widespread pain conditions (CWP) such as the pain associated with fibromyalgia syndrome (FMS) are significant health problems with unclear aetiology. Although CWP and FMS can alter both central and peripheral pain mechanisms, there are no validated markers for such alterations. Pro-and anti-inflammatory components of the immune system such as cytokines and endogenous lipid mediators could serve as systemic markers of alterations in chronic pain. Lipid mediators associated with anti-inflammatory qualities - e.g., oleoylethanolamide (OEA), palmitoylethanolamide ( PEA), and stearoylethanolamide ( SEA) - belong to N-acylethanolamines (NAEs). Previous studies have concluded that these lipid mediators may modulate pain and inflammation via the activation of peroxisome proliferator activating receptors (PPARs) and the activation of PPARs may regulate gene transcriptional factors that control the expression of distinct cytokines. Methods: This study investigates NAEs and cytokines in 17 women with CWP and 21 healthy controls. Plasma levels of the anti-inflammatory lipids OEA, PEA, and SEA, the pro-inflammatory cytokines TNF-alpha, IL-1 beta, IL-6, and IL-8, and the anti-inflammatory cytokine IL-10 were investigated. T-test of independent samples was used for group comparisons. Bivariate correlation analyses, and multivariate regression analysis were performed between lipids, cytokines, and pain intensity of the participants. Results: Significantly higher levels of OEA and PEA in plasma were found in CWP. No alterations in the levels of cytokines existed and no correlations between levels of lipids and cytokines were found. Conclusions: We conclude that altered levels of OEA and PEA might indicate the presence of systemic inflammation in CWP. In addition, we believe our findings contribute to the understanding of the biochemical mechanisms involved in chronic musculoskeletal pain.
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| 17. |
- Stensson, Niclas, 1974-
(författare)
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Endocannabinoids and Related Lipids in Chronic Pain : Analytical and Clinical Aspects
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In Europe, approximately one in five adults experience chronic pain, pain that lasts more than three months. Chronic pain is a significant problem not only for those people suffering from chronic pain but also for society. The prevalence of chronic pain is higher in women and lower socioeconomic groups. Although chronic pain often originates in a specific site, it may eventually spread to several sites, transforming into chronic widespread pain (CWP), a condition evident in about 10% of the adult population. Approximately 1.2-5.4% are classified with fibromyalgia (FM). In addition to CWP, common symptoms of FM include, stiffness, fatigue, sleep disturbances, and cognitive dysfunction and common co-morbidities include depression and anxiety. Although FM/CWP has been reported to alter both central and peripheral nociceptive mechanisms, no objective biomarkers have been found that correlate with CWP/FM and no standard examinations such as blood test, X-ray or computed tomography can provide support for a diagnosis. Because there are no objective biomarkers that correlate with the pathophysiological processes associated with CWP/FM, this debilitating disease is difficult to diagnose and ultimately treat. However, there are some promising therapeutic targets for chronic pain with inter alia analgesic, anti-inflammatory, and stress modulating properties: the endocannabinoids (ECs) arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) and their related lipids oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA).This thesis investigates whether ECs and the related N-acylethanolamines (NAEs) can be used as potential biomarkers for CWP/FM. Specifically, the studies compared the peripheral and systemic levels of ECs and NAEs in 121 women with CWP/FM and in 137 healthy controls in two different cohorts. In addition, the correlation between lipid levels and common pain characteristics such as intensity, sensitivity, and duration were investigated. The EC and related lipid levels were measured using liquid chromatography in combination with tandem mass spectrometry. Multivariate data analysis was used for biomarker evaluation.Compared to the healthy controls, the CWP/FM patients had significantly higher concentrations of OEA, PEA, and SEA in muscle and plasma (p ≤ 0.05) and significantly higher 2-AG in plasma (p ≤ 0.01). These results may indicate that NAEs, are mobilized differently in painful muscles compared with pain free muscles. Moreover, increased systemic levels of NAEs and 2-AG in patients might be signs of ongoing low-grade inflammation inCWP/FM. These findings contribute to a better understanding of how peripheral and systemic factors maintain and activate chronic pain. Although the investigated lipids have statistically significant effects but biologically uncertain role in the clinical manifestations of CWP/FM. Thus plasma lipids are not a good biomarker for CWP/FM. Nevertheless, increased lipid levels indicate a metabolic asymmetry in CWP/FM, a finding that could serve as a basis for more research on pain management.
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| 18. |
- Stensson, Niclas, et al.
(författare)
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High levels of endogenous lipid mediators (N-acylethanolamines) in women with chronic widespread pain during acute tissue trauma
- 2016
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Ingår i: Molecular Pain. - : SAGE PUBLICATIONS INC. - 1744-8069. ; 12:1744806916662886
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Tidskriftsartikel (refereegranskat)abstract
- Although chronic widespread musculoskeletal pain is a significant health problem, the molecular mechanisms involved in developing and maintaining chronic widespread musculoskeletal pain are poorly understood. Central sensitization mechanisms maintained by stimuli from peripheral tissues such as muscle have been suggested. Lipid mediators with anti-inflammatory characteristics such as endogenous ligands of peroxisome proliferator activating receptor-alpha, oleoylethanolamide, and palmitoylethanolamide are suggested to regulate nociceptive transmission from peripheral locations on route towards the central nervous system. This case-control study investigates the levels of anti-inflammatory lipids in microdialysis samples collected during the first 2 h after microdialysis probe insertion and explores the association of these lipids with different pain characteristics in women with chronic widespread musculoskeletal pain (n = 17) and female healthy controls (n = 19). The levels of oleoylethanolamide, palmitoylethanolamide, and stearoylethanolamide were determined. During sampling of dialysate, pain ratings were conducted using a numeric rating scale. Pain thresholds were registered from upper and lower parts of the body. Oleoylethanolamide and stearoylethanolamide levels were significantly higher (p amp;lt;= 0.05) in chronic widespread musculoskeletal pain at all time points. Numeric rating scale correlated with levels of stearoylethanolamide in chronic widespread musculoskeletal pain. Higher levels of lipid mediators could reflect an altered tissue reactivity in response to microdialysis probe insertion in chronic widespread musculoskeletal pain.
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| 19. |
- Stensson, Niclas, et al.
(författare)
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Identification of Lipid Mediators in Peripheral Human Tissues Using an Integrative In Vivo Microdialysis Approach
- 2016
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Ingår i: Journal of analytical and bioanalytical techniques. - : Omics. - 2155-9872. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Endocannabinoids and related N-acylethanolamines (NAEs) are lipid mediators involved in a number of physiological and pathological mechanisms in peripheral tissues. Microdialysis (MD) technique allows continues sampling of endogenous substances in the interstitial fluids of the tissues. The main limitation of MD sampling of lipophilic compounds is low recovery due to adsorption to the MD system and particularly to the catheter membranes. In this in vivo study microdialysate samples were collected from human trapezius muscle and forearm skin. The levels of arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) were analyzed in both microdialysate and in catheter membrane samples using liquid chromatography tandem mass spectrometry.OEA, PEA and SEA were identified in all microdialysate and catheter membrane samples from trapezius and skin. 2-AG was found in all catheter membrane samples from both tissues but not in the actual microdialysate.In conclusion sampling of OEA, PEA and SEA was achievable from trapezius and skin with the presented MD set-up. 2-AG is present in both trapezius muscle and skin tissue but adsorbs to the membranes in a higher extent than the NAEs. Furthermore, consideration of data conserved in the membrane during an MD experiment could be a relevant and more broadly applicable extension of MD sampling methodology which could fill an "information gap" and enhance an adequate interpretation of microdialysate data outcomes.
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| 20. |
- Stensson, Niclas, 1974-, et al.
(författare)
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The Relationship of Endocannabinoidome Lipid Mediators With Pain and Psychological Stress in Women With Fibromyalgia: A Case-Control Study
- 2018
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Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 19:11, s. 1318-1328
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Tidskriftsartikel (refereegranskat)abstract
- Characterized by chronic widespread pain, generalized hyperalgesia, and psychological stress, fibromyalgia (FM) is difficult to diagnose and lacks effective treatments. Endocannabinoids arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG), and the related oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) are endogenous lipid mediators with analgesic and anti-inflammatory characteristics, in company with psychological modulating properties (eg, stress and anxiety), and are included in a new emerging "ome," the endocannabinoidome. This case-control study compared the concentration differences of AEA, OEA, PEA, SEA, and 2 AG in 104 women with FM and 116 healthy control subjects. All participants rated their pain, anxiety, depression, and current health status. The relationships between the lipid concentrations and the clinical assessments were investigated using powerful multivariate data analysis and traditional bivariate statistics. The concentrations of OEA, PEA, SEA, and 2-AG were significantly higher in women with FM than in healthy control subjects; significance remained for OEA and SEA after controlling for body mass index and age. 2-AG correlated positively with FM duration and body mass index, and to some extent negatively with pain, anxiety, depression, and health status. In FM, AEA correlated positively with depression ratings. The elevated circulating levels of endocannabinoidome lipids suggest that these lipids play a role in the complex pathophysiology of FM and might be signs of ongoing low-grade inflammation in FM. Although the investigated lipids are significantly altered in FM, their biological roles are uncertain with respect to the clinical manifestations of FM. Thus plasma lipids alone are not good biomarkers for FM. Perspective: This study reports about elevated plasma levels of endocannabinoidome lipid mediators in FM. The lipids' suitability to work as biomarkers for FM in the clinic were low; however, their altered levels indicate that a metabolic asymmetry is ongoing in FM, which could serve as a baseline during explorative FM pain management. (C) 2018 by the American Pain Society
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| 21. |
- Turkina, Maria V, 1973-, et al.
(författare)
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Evaluation of dynamic changes in interstitial fluid proteome following microdialysis probe insertion trauma in trapezius muscle of healthy women
- 2017
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Microdialysis ( MD) has been shown to be a promising technique for sampling of biomarkers. Implantation of MD probe causes an acute tissue trauma and provokes innate response cascades. In order to normalize tissue a two hours equilibration period for analysis of small molecules has been reported previously. However, how the proteome profile changes due to this acute trauma has yet to be fully understood. To characterize the early proteome events induced by this trauma we compared proteome in muscle dialysate collected during the equilibration period with two hours later in "post-trauma". Samples were collected from healthy females using a 100 kDa MW cut off membrane and analyzed by high sensitive liquid chromatography tandem mass spectrometry. Proteins involved in stress response, immune system processes, inflammatory responses and nociception from extracellular and intracellular fluid spaces were identified. Sixteen proteins were found to be differentially abundant in samples collected during first two hours in comparison to "post-trauma". Our data suggests that microdialysis in combination with mass spectrometry may provide potentially new insights into the interstitial proteome of trapezius muscle, yet should be further adjusted for biomarker discovery and diagnostics. Moreover, MD proteome alterations in response to catheter injury may reflect individual innate reactivity.
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| 22. |
- Wåhlén, Karin, et al.
(författare)
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Plasma Protein Pattern Correlates With Pain Intensity and Psychological Distress in Women With Chronic Widespread Pain
- 2018
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Ingår i: Frontiers in Psychology. - : FRONTIERS MEDIA SA. - 1664-1078. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Although generalized muscle pain, tiredness, anxiety, and depression are commonly present among chronic widespread pain (CWP) patients, the molecular mechanisms behind CWP are not fully elucidated. Moreover, the lack of biomarkers often makes diagnosis and treatment problematic. In this study, we investigated the correlation between pain intensity, psychological distress, and plasma proteins among CWP patients and controls (CON). Methods: The plasma proteome of CWP (n = 15) and CON (n = 23) was analyzed using two-dimensional gel electrophoresis. Orthogonal Partial Least Square analysis (OPLS) was used to determine proteins associated with pain intensity (numeric rating scale) in CWP and psychological distress (Hospital and Depression Scale, HADS) in CWP and CON. Significant proteins were identified by MALDI-TOF and tandem MS. Results: In CWP, pain intensity was associated with plasma proteins mostly involved in metabolic and immunity processes (e.g., kininogen-1, fibrinogen gamma chain, and ceruloplasmin), and psychological distress was associated with plasma proteins related to immunity response, iron ion, and lipid metabolism (e.g., complement factor B, complement C1r subcomponent, hemopexin, and clusterin). Discussion: This study suggests that different plasma protein patterns are associated with different pain intensity and psychological distress in CWP. Proteins belonging to the coagulation cascade and immunity processes showed strong associations to each clinical outcome. Using the plasma proteome profile of CWP to study potential biomarker candidates provides a snapshot of ongoing systemic mechanisms in CWP.
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| 23. |
- Wåhlén, Karin, et al.
(författare)
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Systemic alterations in plasma proteins from women with chronic widespread pain compared to healthy controls: a proteomic study
- 2017
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Ingår i: Journal of Pain Research. - : DOVE MEDICAL PRESS LTD. - 1178-7090. ; 10, s. 797-809
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Tidskriftsartikel (refereegranskat)abstract
- Chronic widespread pain (CWP) is a complex pain condition that is difficult to treat. The prevalence of CWP approximates similar to 10% of the general population, with higher prevalence in women. Lack of understanding of molecular mechanisms has been a challenge for diagnosis and treatment of chronic pain. The aim of this study was to explore the systemic protein changes in CWP compared to those in healthy controls (CON). By applying 2-dimensional gel electrophoresis, we analyzed the protein pattern of plasma samples from women with CWP (n=16) and healthy women (n=23). The proteomic data were analyzed using multivariate statistical models, and altered proteins were identified using mass spectrometry. The proteome analysis was further validated by gel-free Western blot. Multivariate statistical data analysis of quantified proteins revealed 22 altered proteins in women with CWP, compared to CON group. Many of the identified proteins are previously known to be involved in different parts of the complement system and metabolic and inflammatory processes, e.g., complement factor B, vitamin D-binding protein, ceruloplasmin, transthyretin and alpha-2-HS-glycoprotein. These results indicate that important systemic protein differences exist between women with CWP and healthy women. Further, this study illustrates the potential use of proteomics to detect biomarkers that may provide new insights into the molecular mechanism(s) of chronic pain. However, further larger investigations are required in order to confirm these findings before it will be possible to identify proteins as potential pain biomarkers for clinical use.
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| 24. |
- Fowler, Christopher J, et al.
(författare)
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Does the hydrolysis of 2-arachidonoylglycerol regulate its cellular uptake?
- 2008
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Ingår i: Pharmacol Res. - 1043-6618. ; 58:1, s. 72-6
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Very little is known about the processes regulating the cellular uptake of the endogenous cannabinoid 2-arachidonoylglycerol (2-AG). In the present study, we investigated whether inhibition of 2-AG hydrolysis reduced its uptake, i.e. whether this compound behaves in a manner analogous to the related endocannabinoid anandamide. The selective fatty acid amide hydrolase inhibitor URB597 (3'-(aminocarbamoyl)[1,1'-biphenyl]-3-yl)-cyclohexylcarbamate) completely blocked the hydrolysis of anandamide and reduced its uptake by about half in RBL2H3 basophilic leukaemia cells. In contrast, in these cells, in PC3 and R3327AT-1 prostate cancer cells and in Neuro-2a neuroblastoma cells, the compound had more modest effects upon the hydrolysis of 2-AG and did not affect its cellular uptake at all, indicating that in these cells fatty acid amide hydrolase does not regulate the uptake of 2-AG. The serine hydrolase inhibitor methylarachidonoyl fluoronophosphonate behaved like URB597 with respect to anandamide uptake by RBL2H3 and Neuro-2a cells, and inhibited the hydrolysis of 2-AG with IC(50) values of 0.014, 0.052, 0.41 and approximately 1muM for RBL2H3, PC3, AT-1 and Neuro-2a cells, respectively. MAFP (1muM) did not significantly reduce the uptake of 2-AG by RBL2H3, PC3 and AT-1 cells but did reduce the uptake of this endocannabinoid by Neuro-2a cells. Arachidonoyl trifluoromethyl ketone and URB602 ([1,1'-biphenyl]-3-yl-carbamic acid, cyclohexyl ester) reduced the uptake of 2-AG by both RBL2H3 and Neuro-2a cells, but at the high concentrations needed, the compound also blocked the retention of these ligands by wells. It is concluded that unlike the situation for anandamide, hydrolysis of 2-AG does not regulate its cellular uptake in RBL2H3, AT-1 and PC3 cells, but may gate the uptake in Neuro-2a cells
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| 25. |
- Ghafouri, Nazdar, et al.
(författare)
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Effects of interdisciplinary pain rehabilitation programs on neuropathic and non-neuropathic chronic pain conditions – a registry-based cohort study from Swedish Quality Registry for Pain Rehabilitation (SQRP)
- 2023
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Ingår i: BMC Musculoskeletal Disorders. - : BMC. - 1471-2474. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background and aim: Neuropathic pain arises as a direct consequence of a lesion or disease affecting the somatosensory system. Pharmacological treatments for neuropathic pain often fail despite following guidelines. Interdisciplinary Pain Rehabilitation Programs (IPRP) are an effective intervention for chronic pain conditions. Little research has investigated whether IPRP can benefit patients with chronic neuropathic pain compared to other chronic pain conditions. This study assesses the real-world effects of IPRP on patients with chronic neuropathic pain compared to non-neuropathic patients using Patient-Reported Outcome Measures (PROMs) available in the Swedish Quality Registry for Pain Rehabilitation (SQRP). Methods: A neuropathic group of patients (n = 1,654) were identified in two steps. This group was compared to a non-neuropathic group (n = 14,355) composed of common diagnoses (low back pain, fibromyalgia, whiplash associated disorders, and Ehlers-Danlos Syndrome) in relation to background variables, three overall outcome variables, and mandatory outcome variables (pain intensity, psychological distress symptoms, activity/participation aspects and health-related quality of life variables). Of these patients 43–44% participated in IPRP. Results: At assessment, the neuropathic group reported significantly (with small effect sizes (ES)) more physician visits the previous year, older age, shorter pain durations, and less spatial extent of the pain (moderate ES). Moreover, for the 22 mandatory outcome variables, we found only clinically insignificant differences according to ESs between the groups. For patients participating in IPRP, the neuropathic group displayed equal or in some cases slightly superior results compared to the non-neuropathic group. Discussion and conclusion: After assessing the real-world effects of IPRP, this large study found that neuropathic pain patients can benefit from the IPRP intervention. Both registry studies and RCTs are needed to better understand which patients with neuropathic pain are most suitable for IPRP and to what extent special considerations need to be made for these patients within the framework of IPRP.
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| 26. |
- Ghafouri, Nazdar, 1980-
(författare)
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Endocannabinoids and N-acylethanolamines in translational pain research : from monoacylglycerol lipase to muscle pain
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the early nineties cannabinoid receptors, the main target for Δ9-tetrahydrocannabinol (THC), the psychoactive component of marijuana were identified. Shortly after their endogenous ligands, N-arachidonoylethanolamine (anandamide, AEA) and 2-diacylglycerol (2-AG) were characterized. The enzymes primarily responsible for catalysing the degradation of AEA and 2-AG are fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL) respectively. AEA is a member of the N-acylethanolamine (NAE) class of lipids, which depending on the acyl chain length and number of double bonds can act as ligands for a variety of biological targets. Exogenous cannabinoids have long been reported to have analgesic effects, however the clinical usefulness of such substances is limited by their psychoactive effects. Inhibition of endocannabinoid degradation would mean enhancing the therapeutic effects without producing these unwanted side effects. In order to succeed in developing such compounds the pharmacology of the enzymes responsible for the degradation of endocannabinoids has to be thoroughly understood. When the preclinical part of this thesis was planned, FAAH had been well characterized whereas little was known as to the pharmacology of MGL. A series of compounds were tested in this first study aiming to find MGL-selective compounds. Although no compounds showed selectivity for MGL over FAAH, several interesting agents affecting both enzymes were identified.In order to increase the knowledge concerning which patient group would benefit from such treatment strategies it is important to investigate in which pain states the endocannabinoids/NAEs are altered. Thus the general aim of the clinical part of this thesis was to investigate the levels of endocannabinoids/NAEs in the interstitium of the trapezius muscle in women suffering from chronic neck/shoulder pain (CNSP) and chronic wide spread pain (CWP) and in healthy pain-free controls. Furthermore for the CNSP the effect of training, which is a commonly recommended treatment for these patients, on the levels of endocannabinoids/NAEs was also investigated. Microdialysis technique in the trapezius muscle was used for sampling and masspectrometry was used for analysing. Two NAEs,N-palmitoylethanolamine (PEA) and N-stearoylethanolamine (SEA), could be repeatedly measured. The levels of these two lipids were significantly higher in CNSP compared to CON. The result showed also that PEA and SEA mobilize differently in CWP compared to both CNSP and CON. Taken together the results presented in thesis represent an early characterization of the pharmacology of MGL and provides novel information on NAEs in chronic muscle pain.
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| 27. |
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| 28. |
- Lind, Jonas, et al.
(författare)
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Levels of bioactive endogenous lipids and health-related quality of life in Chronic Idiopathic Axonal Polyneuropathy
- 2022
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 127
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although neuropathic pain is a significant problem in polyneuropathy, the underlying molecular mechanisms are poorly understood. The endogenous bioactive lipids 2-arachidonoyl-glycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) are known to influence pain and inflammation in the peripheral nervous system. The aim of this study was to explore the plasma levels of endocannabinoids and related lipids and health-related quality of life in patients with polyneuropathy with and without pain.Methods: Patients (n = 48) with Chronic Idiopathic Axonal Neuropathy were included. Clinical data were retrieved from medical files. All patients filled out the SF-36 and EQ-5D questionnaires. In addition, blood samples were analyzed for 2-AG, OEA, PEA, and SEA.Results: Neuropathic pain was reported in 21 of the patients. There were significantly lower levels of 2-AG in patients with neuropathic pain (P = 0.03), but there were no significant differences in OEA (P = 0.61), PEA (P = 0.95), or SEA (P = 0.97) levels. The patients reporting pain in the hands had significantly lower SEA levels, 10.0 versus 15.0 (P = 0.03). The levels of 2-AG were significantly higher among patients reporting paresthesia in their feet (80.1 vs. 56.3; P = 0.02). Levels of PEA, SEA, and 2-AG were decreased in patients with loss of vibration. PEA and SEA were decreased in patients with loss of pain and temperature, and SEA decreased in patients with loss of sense of touch. However, the differences in the levels of bioactive endogenous lipids were not statistically significant when corrected for multiple comparisons.Conclusion: Alterations of 2-AG levels between polyneuropathy patients with and without neurogenic pain indicate that it could play an essential role. Further studies are warranted.
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| 29. |
- Mattsson, Anna, et al.
(författare)
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The treatment lottery of chronic back pain? A case series at a multidisciplinary pain centre
- 2023
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Ingår i: Scandinavian Journal of Pain. - : WALTER DE GRUYTER GMBH. - 1877-8860 .- 1877-8879. ; 23:2, s. 273-283
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesDespite the number of people affected by chronic back pain, and the many available treatment options, even the best modalities provide limited pain reduction on a group level, often without simultaneous improvements in functioning or health-related quality of life. The objective was to provide an overview of the treatment of chronic back pain in clinical practice at a multidisciplinary pain centre, and to study patient and pain characteristics in different treatment groups.Methods104 chronic back pain patients (primary ICD-10-SE-diagnosis M53.0-M54.9 excluding M54.1 and M54.3), referred to the Pain and Rehabilitation Centre, University Hospital, Linkoping in 2015, were studied using data from the Swedish Quality Registry for Pain Rehabilitation, self-reported medication data, and a retrospective medical record review.ResultsThe following treatment groups were identified: rehabilitation (n=21), analgesics (n=33), invasive intervention (n=14), and no treatment (n=35). Significant differences between groups were found with regards to age, sick leave, education level, persisting pain duration, punishing responses by significant other, previous invasive intervention, receiving sub-clinic, physician speciality and referring care level.ConclusionsOverall, patient demographics were associated with treatment strategy to a higher degree than patient-reported outcome measures. Moreover, physician speciality and organisational factors seemed to play a role in treatment choice.
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| 30. |
- Nilsson, Ellinor, et al.
(författare)
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Managing Fatigue: Experiences From a 6-week Course for Adults With Cerebral Palsy
- 2023
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Ingår i: Archives of Rehabilitation Research and Clinical Translation. - : ELSEVIER. - 2590-1095. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore experiences of a 6-week Fatigue Management course (FMC) in adults with cerebral palsy (CP).Design: A qualitative study using semi-structured interviews. The study process followed the Consolidated Criteria for Reporting Qualitative Research (COREQ).Setting: The study was conducted in southeastern Sweden in an out-patient setting.Participants: Adults (N=8) with CP who had participated in FMC. Interventions: Not applicable.Main Outcome Measure: Qualitative content analysis of the transcribed interviews led to identification of a main category, categories, and subcategories, describing the participants' experiences of FMC.Results: The analysis identified 2 categories: Awareness regarding fatigue, with the 2 subcategories: A better understanding, and The feeling of not being alone; and Perceive opportunities for changes, with the 3 subcategories: Understanding the need for changes, Demanding process, and Taking steps toward change. These categories were summed up in the main category describing the participants' experiences of FMC: A challenging and eye-opening course that gave deeper self-understanding and thoughts about making changes.
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