| 1. |
- Ernberg, Malin, et al.
(författare)
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Altered Plasma Proteins in Myogenous Temporomandibular Disorders
- 2022
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Ingår i: Journal of Clinical Medicine. - Basel, Switzerland : MDPI. - 2077-0383. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were (1) to compare the levels and interactions of several plasma proteins in patients with myogenous temporomandibular disorders (TMDM) compared to healthy and pain-free controls, (2) to compare the levels and interactions in two TMDM subgroups, myalgia (MYA) and myofascial pain (MFP), and (3) to explore associations between the proteins and clinical data. Thirty-nine patients with TMDM (MFP, n = 25, MYA, n = 14), diagnosed according to the diagnostic criteria for TMD (DC/TMD), aged 38 years, and sex-matched pain-free controls completed an extended DC/TMD Axis II questionnaire and the plasma concentration of 87 biomarkers were analyzed. Nine proteins separated TMDM from controls (p = 0.0174) and 12 proteins separated MYA from MFP (p = 0.019). Pain duration, characteristic pain intensity, pain catastrophizing, perceived stress, and insomnia severity were significantly associated with protein markers (p < 0.001 to p < 0.022). In conclusion, several plasma proteins were upregulated in TMDM and either upregulated or downregulated in MYA compared to MFP. Some proteins in TMDM were associated with pain variables, sleep disturbance, and emotional function. These results show that systemic differences in protein expression exist in patients with TMDM and that altered levels of specific plasma proteins are associated with different clinical variables.
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| 2. |
- Gerdle, Björn, 1953-, et al.
(författare)
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Plasma protein patterns are strongly correlated with pressure pain thresholds in women with chronic widespread pain and in healthy controls-an exploratory case-control study
- 2020
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Ingår i: Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0025-7974 .- 1536-5964. ; 99:22
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Tidskriftsartikel (refereegranskat)abstract
- Chronic widespread pain (CWP) is a complex pain condition characterized by generalized musculoskeletal pain and often associated with other symptoms. An important clinical feature is widespread increased pain sensitivity such as lowered pain thresholds for mechanical stimuli (pressure pain thresholds [PPT]). There is a growing interest in investigating the activated neurobiological mechanisms in CWP, which includes fibromyalgia. In CWP, strong significant correlations have been found between muscle protein patterns and PPT. This explorative proteomic study investigates the multivariate correlation pattern between plasma proteins and PPT in CWP and in healthy controls (CON). In addition, this study analyses whether the important proteins for PPT differ between the 2 groups. Using 2-dimensional gel electrophoresis, we analyzed the plasma proteome of the CWP (n = 15) and the CON (n = 23) and proteins were identified using mass spectrometry. For both the CWP and the CON, the associations between the identified proteins and PPT were analyzed using orthogonal partial least square in 2 steps. Significant associations between certain plasma proteins and PPT existed both in CWP (R-2 = 0.95;P = .006) and in CON (R-2 = 0.89;P < .001). For both groups of subjects, we found several proteins involved in PPT that reflect different biological processes. The plasma proteins as well as the biological processes involved in PPT differed markedly between the 2 groups of subjects. This study suggests that plasma protein patterns are associated with pain thresholds in CWP. Using the plasma proteome profile of CWP to study potential biomarker candidates could provide a snapshot of ongoing systemic mechanisms in CWP.
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| 3. |
- Ghafouri, Bijar, et al.
(författare)
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The Vastus Lateralis Muscle Interstitium Proteome Changes after an Acute Nociception in Patients with Fibromyalgia Compared to Healthy Subjects-A Microdialysis Study
- 2023
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Fibromyalgia (FM) is a complex disorder and a clinical challenge to diagnose and treat. Microdialysis is a valuable tool that has been used to investigate the interstitial proteins and metabolites of muscle in patients with fibromyalgia. The implantation of the catheter in the muscle causes acute tissue trauma and nociception. The aim of this study was to investigate acute proteome changes in the vastus lateralis muscle in women fibromyalgia patients (FM) and healthy subjects (CON). A further aim was to study if a 15-week resistance exercise program in FM had any influence on how chronic painful muscle responds to acute nociception. Twenty-six women patients with FM and twenty-eight CON were included in this study. A microdialysis catheter (100 kilo Dalton cut off, membrane 30 mm) was inserted in the vastus lateralis muscle, and samples were collected every 20 min. Subjects rated pain before catheter insertion, directly after, and every 20 min of sample collection. Dialysate samples from time points 0-120 were pooled and considered trauma samples due to the catheter insertion. The samples were analyzed with nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). Advanced multivariate data analysis was used to investigate protein profile changes between the groups. Multivariate data analysis showed significant (CV-ANOVA p = 0.036) discrimination between FM and CON based on changes in 26 proteins. After the 15-week exercise intervention, the expression levels of the 15 proteins involved in muscle contraction, response to stimulus, stress, and immune system were increased to the same expression levels as in CON. In conclusion, this study shows that microdialysis, in combination with proteomics, can provide new insights into the interstitial proteome in the muscle of FM. In response to acute nociception, exercise may alter the innate reactivity in FM. Exercise may also modulate peripheral muscle proteins related to muscle contraction, stress, and immune response in patients with FM.
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| 4. |
- Hansson, Lina S., 1992-, et al.
(författare)
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Perception of unfamiliar caregivers during sickness – Using the new Caregiver Perception Task (CgPT) during experimental endotoxemia
- 2024
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Ingår i: Brain, behavior, and immunity. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0889-1591 .- 1090-2139. ; 119, s. 741-749
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Tidskriftsartikel (refereegranskat)abstract
- Social withdrawal is a well-established part of sickness behavior, but in some contexts sick animals might gain from keeping close instead of keeping away. For instance, sick individuals are more willing to be near known individuals who can provide care and safety (close others) compared to when healthy. Yet, interactions with some strangers might also be beneficial (i.e., healthcare professionals), but it is not known how sickness interplay with social behavior towards such individuals. Here, we assessed if sickness affects perception of caregivers, and developed a new task, the Caregiver Perception Task (CgPT). Twenty-six participants performed the CgPT, once after an injection of lipopolysaccharide (LPS, 0.8 ng/kg body weight, n = 24), and once after an injection of saline (n = 25), one hour and forty-five minutes post-injection. During the task, participants watched short video clips of three types of caregivers: a healthcare professional taking care of a sick individual, a healthcare professional not taking care of a sick individual, and a non-healthcare professional taking care of their sick adult child or partner. After each video clip, the likability, trustworthiness, professionalism, and willingness to interact with and receive care from the caregiver were rated on visual analogue scales. Results showed that participants injected with saline rated healthcare professionals who did not take care of a sick individual less positively on all aspects compared to healthcare professionals who took care of a sick individual. Moreover, compared to saline, LPS increased the participants’ willingness to receive care from healthcare professionals and non-healthcare professionals providing care, but not from healthcare professionals not providing care. Thus, our results indicate that sick individuals may approach unknown individuals with potential to provide care and support.
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| 5. |
- Karshikoff, Bianka, et al.
(författare)
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Inflammatory Blood Signature Related to Common Psychological Comorbidity in Chronic Pain
- 2023
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Ingår i: Biomedicines. - : MDPI. - 2227-9059. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Chronic pain is characterized by high psychological comorbidity, and diagnoses are symptom-based due to a lack of clear pathophysiological factors and valid biomarkers. We investigate if inflammatory blood biomarker signatures are associated with pain intensity and psychological comorbidity in a mixed chronic pain population. Eighty-one patients (72% women) with chronic pain (>6 months) were included. Patient reported outcomes were collected, and blood was analyzed with the Proseek Multiplex Olink Inflammation Panel (Bioscience Uppsala, Uppsala, Sweden), resulting in 77 inflammatory markers included for multivariate data analysis. Three subgroups of chronic pain patients were identified using an unsupervised principal component analysis. No difference between the subgroups was seen in pain intensity, but differences were seen in mental health and inflammatory profiles. Ten inflammatory proteins were significantly associated with anxiety and depression (using the Generalized Anxiety Disorder 7-item scale (GAD-7) and the Patient Health Questionnaire (PHQ-9): STAMBP, SIRT2, AXIN1, CASP-8, ADA, IL-7, CD40, CXCL1, CXCL5, and CD244. No markers were related to pain intensity. Fifteen proteins could differentiate between patients with moderate/high (GAD-7/PHQ-9 > 10) or mild/no (GAD-7/PHQ-9 < 10) psychological comorbidity. This study further contributes to the increasing knowledge of the importance of inflammation in chronic pain conditions and indicates that specific inflammatory proteins may be related to psychological comorbidity.
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| 6. |
- Korhonen, Laura, Professor, 1974-, et al.
(författare)
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Multivariate analyses of immune markers reveal increases in plasma EN-RAGE in first-episode psychosis patients
- 2023
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Ingår i: Translational Psychiatry. - : Springer. - 2158-3188. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Immune cells and cytokines are largely recognized as significant factors in the pathophysiology of neuropsychiatric disorders. The possible role of other blood cells such as leukocytes in events of acute psychosis is in contrast only emerging. To study blood-born markers in acute psychosis we here evaluated plasma proteins in drug-naive first-episode psychosis (FEP) patients and healthy controls using a multiplex proximity extension assay technique. We analyzed a panel of 92 immune markers and plasma samples from 60 FEP patients and 50 controls and evaluated the changes obtained using multivariate statistical methods followed by protein pathway analyses. Data showed that 11 proteins are significantly different between FEP patients and healthy controls We observed increases in pro-inflammatory proteins such as interleukin-6, oncostatin-M, and transforming growth factor-alpha in FEP patients compared with controls. Likewise, the extracellular newly identified RAGE-binding protein (EN-RAGE) that regulates the expression of various cytokines was also elevated in the plasma of FEP patients. The results indicate that neutrophil-derived EN-RAGE could play an important role during the early phase of acute psychosis by stimulating cytokines and the immune response targeting thereby likely also the brain vasculature.
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| 7. |
- Tobieson, Lovisa, et al.
(författare)
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Proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients - A pilot study
- 2020
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Ingår i: Proteome Science. - : Springer Science and Business Media LLC. - 1477-5956. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cerebral microdialysis (CMD) is a minimally invasive technique for sampling the interstitial fluid in human brain tissue. CMD allows monitoring the metabolic state of tissue, as well as sampling macromolecules such as proteins and peptides. Recovery of proteins or peptides can be hampered by their adsorption to the CMD membrane as has been previously shown in-vitro, however, protein adsorption to CMD membranes has not been characterized following implantation in human brain tissue. Methods: In this paper, we describe the pattern of proteins adsorbed to CMD membranes compared to that of the microdialysate and of cerebrospinal fluid (CSF). We retrieved CMD membranes from three surgically treated intracerebral hemorrhage (ICH) patients, and analyzed protein adsorption to the membranes using two-dimensional gel electrophoresis (2-DE) in combination with nano-liquid mass spectrometry. We compared the proteome profile of three compartments; the CMD membrane, the microdialysate and ventricular CSF collected at time of CMD removal. Results: We found unique protein patterns in the molecular weight range of 10-35 kDa for each of the three compartments. Conclusion: This study highlights the importance of analyzing the membranes in addition to the microdialysate when using CMD to sample proteins for biomarker investigation.
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| 8. |
- Wåhlén, Karin, 1986-, et al.
(författare)
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Proteomic Investigation in Plasma from Women with Fibromyalgia in Response to a 15-wk Resistance Exercise Intervention
- 2022
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Ingår i: Medicine & Science in Sports & Exercise. - Philadelphia, PA, United States : Ovid Technologies (Wolters Kluwer Health). - 0195-9131 .- 1530-0315. ; 54:2, s. 232-246
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Tidskriftsartikel (refereegranskat)abstract
- PurposeFibromyalgia (FM) is a complex pain condition, and exercise is considered the first option of treatment. Few studies have examined the effect of exercise on molecular mechanisms in FM. The aim of this study was to analyze the plasma proteome in women with FM and healthy controls (CON) before and after 15 wk of resistance exercise. This study further investigated whether clinical and exercises-related outcomes correlated with identified plasma proteins in FM.MethodsPlasma samples from 40 FM/25 CON (baseline) and 21 FM/24 CON (postexercise) were analyzed using shotgun proteomics. Clinical/background data were retrieved through questionnaires. Exercise-related variables and pressure pain thresholds were assessed using standardized instruments. Multivariate statistics were applied to analyze the proteomic profile at baseline and postexercise, and correlation with clinical/exercise-related data.ResultsFifteen weeks of resistance exercises improved clinical symptoms and muscle strength, and affected circulating proteins related to immunity, stress, mRNA stability, metabolic processes, and muscle structure development in FM. Pressure pain threshold was related to a specific protein profile, with proteins involved in metabolic and immune response. Subgroups of FM based on plasma proteins, FM duration, and improved muscle strength were identified.ConclusionsExercise seems to affect circulating proteins, clinical characteristics, and muscle strength in FM. This study contributes to better understanding of systemic protein changes in FM compared with CON and how resistance exercise affects such changes.
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| 9. |
- Wåhlén, Karin, 1986-, et al.
(författare)
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Significant correlation between plasma proteome profile and pain intensity, sensitivity, and psychological distress in women with fibromyalgia
- 2020
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Fibromyalgia (FM) is a complex pain condition where the pathophysiological and molecular mechanisms are not fully elucidated. The primary aim of this study was to investigate the plasma proteome profile in women with FM compared to controls. The secondary aim was to investigate if plasma protein patterns correlate with the clinical variables pain intensity, sensitivity, and psychological distress. Clinical variables/background data were retrieved through questionnaires. Pressure pain thresholds (PPT) were assessed using an algometer. The plasma proteome profile of FM (n=30) and controls (n=32) was analyzed using two-dimensional gel electrophoresis and mass spectrometry. Quantified proteins were analyzed regarding group differences, and correlations to clinical parameters in FM, using multivariate statistics. Clear significant differences between FM and controls were found in proteins involved in inflammatory, metabolic, and immunity processes. Pain intensity, PPT, and psychological distress in FM had associations with specific plasma proteins involved in blood coagulation, metabolic, inflammation and immunity processes. This study further confirms that systemic differences in protein expression exist in women with FM compared to controls and that altered levels of specific plasma proteins are associated with different clinical parameters.
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| 10. |
- Wåhlén, Karin, 1986-
(författare)
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The pain profile in fibromyalgia : Painomic studies of pain characteristics and proteins in blood
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic widespread pain (CWP), including fibromyalgia (FM), is a complex pain condition, where little is known about the molecular mechanisms contributing to its pathophysiology. To date, there are no established biomarkers for CWP/FM. This thesis has investigated potential molecular mechanisms and biomarkers in blood for chronic pain in women with CWP/FM. Furthermore, investigations are made to evaluate whether common pain characteristics such as pain intensity, sensitivity, and psychological distress in CWP/FM are correlated with specific proteins in blood.The pain profile of CWP/FM, which includes the plasma proteome and clinical characteristics, is analyzed using proteomics, advanced multivariate statistics, and bioinformatics. The results from paper I, III, and IV indicate that there are prominent systemic changes related to immunity, inflammation, and metabolic processes in women with CWP/FM compared to healthy controls. Furthermore, paper II and III show that in CWP/FM, pain intensity is related to protein profiles involved in immunity processes, psychological distress with metabolic and immunity processes, and pain sensitivity with inflammatory processes.In paper IV, the plasma proteome is investigated before and after a 15 weeks resistance exercise intervention in FM and healthy controls. Both at baseline and post exercise in FM and controls, prominent protein alterations are found that are involved in immunity, stress, mRNA stability, and muscle structure development. Exercise seems to influence clinical characteristics and circulating proteins in FM. Furthermore, specific plasma proteome profile is found related to grade of chronification, pain sensitivity, and improved muscle force of the quadriceps muscle.To summarize, the results from this thesis suggest that in CWP/FM there might be a dysregulation in the biological processes involved in the immune system and metabolic processes, which are tightly linked to several proteins in the complement system and blood coagulation cascade. These results shed light on potential ongoing mechanisms involved in the pathophysiology of the complex pain condition CWP/FM. This type of biomarker research has a large potential in increasing knowledge about mechanisms involved in CWP/FM and can hereby open for better clinical understanding and management of this and other chronic pain states. The clinical value of collecting a blood sample and measuring stable pain mechanism markers in combination with evaluation of anamnesis and clinical examination would in the future help clinicians and patients receive a faster and more precise diagnosis and ultimately better treatment strategies.
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