| 1. |
- Krarup, Anne L., et al.
(författare)
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The Short Health Scale A Simple, Valid, Reliable, and Responsive Way of Measuring Subjective Health in Patients With Irritable Bowel Syndrome
- 2015
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Ingår i: Journal of Clinical Gastroenterology. - : Lippincott, Williams andamp; Wilkins: No Hybrid Open Access. - 0192-0790 .- 1539-2031. ; 49:7, s. 565-570
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Tidskriftsartikel (refereegranskat)abstract
- Goals:To evaluate validity, reliability, and responsiveness of the Short Health Scale (SHS) in irritable bowel syndrome (IBS) patients.Background:Subjective health assessment is central when treating patients with IBS. The Short Health Scale is a quick 4-item questionnaire covering most aspects of subjective health that has been validated for inflammatory bowel disease.Study:To test validity, 451 patients with IBS (mean age, 38 y; 81% females) completed the SHS and questionnaires assessing IBS symptom severity (IBS-SSS), gastrointestinal (GI)-specific anxiety (VSI), and quality of life (IBSQOL). To evaluate reliability and responsiveness to changes, the questionnaires were repeated after 2 weeks in 18 patients, and after 12 weeks in 212 patients who had completed a patient-education program.Results:Validity was documented with (1) gradually increasing mean scores for all 4 SHS items with increasing IBS-SSS (Pless than0.0001), and (2) correlations between the 4 SHS items and the corresponding items from the other subjective health assessment tools [item 1 (symptom burden): =0.67, item 2 (daily function): =-0.44 to -0.46, item 3 (disease-related worry): =-0.51 to 0.57, item 4 (general well-being): =-0.34 to -0.46, Pless than0.0001]. Reliability was confirmed (Spearman greater than0.7 and intraclass correlations greater than0.7). Responsiveness was good with responders to the patient-education program (IBS-SSS reduction 50 points) having significant reductions in 3 of the SHS items (Pless than0.05), and borderline change for the fourth SHS item (P=0.06).Conclusions:SHS is a health measure that shows promising evidence of validity, reliability, and responsiveness in IBS patients. It is quickly completed and evaluated, which supports its usefulness in the busy clinical practice.
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| 2. |
- Aarnio, Mikko, et al.
(författare)
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Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.
- 2017
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Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter. - 1877-8860 .- 1877-8879. ; 17:1, s. 418-424
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Positron emission tomography (PET) with the radioligand [(11)C]-D-deprenyl has shown increased signal at location of pain in patients with rheumatoid arthritis and chronic whiplash injury. The binding site of [(11)C]-D-deprenyl in peripheral tissues is suggested to be mitochondrial monoamine oxidase in cells engaged in post-traumatic inflammation and tissue repair processes. The association between [(11)C]-D-deprenyl uptake and the transition from acute to chronic pain remain unknown. Further imaging studies of musculoskeletal pain at the molecular level would benefit from establishing a clinical model in a common and well-defined injury in otherwise healthy and drug-naïve subjects. The aim of this study was to investigate if [(11)C]-D-deprenyl uptake would be acutely elevated in unilateral ankle sprain and if tracer uptake would be reduced as a function of healing, and correlated with pain localizations and pain experience.METHODS: Eight otherwise healthy patients with unilateral ankle sprain were recruited at the emergency department. All underwent [(11)C]-D-deprenyl PET/CT in the acute phase, at one month and 6-14 months after injury.RESULTS: Acute [(11)C]-D-deprenyl uptake at the injury site was a factor of 10.7 (range 2.9-37.3) higher than the intact ankle. During healing, [(11)C]-D-deprenyl uptake decreased, but did not normalize until after 11 months. Patients experiencing persistent pain had prolonged [(11)C]-D-deprenyl uptake in painful locations.CONCLUSIONS AND IMPLICATIONS: The data provide further support that [(11)C]-D-deprenyl PET can visualize, quantify and follow processes in peripheral tissue that may relate to soft tissue injuries, inflammation and associated nociceptive signaling. Such an objective correlate would represent a progress in pain research, as well as in clinical pain diagnostics and management.
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| 3. |
- Ackermann, Paul W., et al.
(författare)
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Tendon pain : what are the mechanisms behind it?
- 2023
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Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter. - 1877-8860 .- 1877-8879. ; 23:1, s. 14-24
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Forskningsöversikt (refereegranskat)abstract
- ObjectivesManagement of chronic tendon pain is difficult and controversial. This is due to poor knowledge of the underlying pathophysiology of chronic tendon pain, priorly known as tendinitis but now termed tendinopathy. The objective of this topical review was to synthesize evolving information of mechanisms in tendon pain, using a comprehensive search of the available literature on this topic.ContentThis review found no correlations between tendon degeneration, collagen separation or neovascularization and chronic tendon pain. The synthesis demonstrated that chronic tendon pain, however, is characterized by excessive nerve sprouting with ingrowth in the tendon proper, which corresponds to alterations oberserved also in other connective tissues of chronic pain conditions. Healthy, painfree tendons are devoid of nerve fibers in the tendon proper, while innervation is confined to tendon surrounding structures, such as sheaths. Chronic painful tendons exhibit elevated amounts of pain neuromediators, such as glutamate and substance p as well as up-regulated expression and excitability of pain receptors, such as the glutamate receptor NMDAR1 and the SP receptor NK1, found on ingrown nerves and immune cells. Increasing evidence indicates that mast cells serve as an important link between the peripheral nervous system and the immune systems resulting in so called neurogenic inflammation.SummaryChronic painful tendons exhibit (1) protracted ingrowth of sensory nerves (2) elevated pain mediator levels and (3) up-regulated expression and excitability of pain receptors, participating in (4) neuro-immune pathways involved in pain regulation. Current treatments that entail the highest scientific evidence to mitigate chronic tendon pain include eccentric exercises and extracorporeal shockwave, which both target peripheral neoinnervation aiming at nerve regeneration.OutlookPotential mechanism-based pharmacological treatment approaches could be developed by blocking promotors of nerve ingrowth, such as NGF, and promoting inhibitors of nerve ingrowth, like semaphorins, as well as blocking glutamate-NMDA-receptor pathways, which are prominent in chronic tendon pain.
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| 4. |
- Ahlqvist, Kerstin, et al.
(författare)
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Generalized joint hypermobility and the risk of pregnancy‐related pelvic girdle pain : Is body mass index of importance?—A prospective cohort study
- 2023
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 102:10, s. 1259-1268
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Pelvic girdle pain (PGP) affects approximately 50% of pregnant women. The mechanisms are multifactorial but not fully understood. Women with generalized joint hypermobility (GJH) may be vulnerable to load in the pelvic joints during pregnancy. Our aim was to investigate if women with GJH had an increased risk of PGP and higher pain intensity during and after pregnancy, compared with women with normal joint mobility. We also studied if body mass index (BMI) in early pregnancy influenced that risk.Material and methods: A prospective cohort study of 356 women, whose data were collected by self-reports and clinical examinations in early and in late pregnancy and 9 months after childbirth. GJH was present with ≥5/9 points on the Beighton score. PGP was defined by a pain drawing and ≥1 positive test. Pain intensity was measured with a visual analogue scale (0-100 mm). We adjusted for age and origin in logistic regression and ordinal logistic regression analysis.Results: In early pregnancy, 47.1% of the women with GJH had PGP vs 32.6% of women with normal joint mobility (adjusted odds ratio [aOR] 1.76; 95% confidence interval [CI] 0.86-3.62) and had higher odds of reporting higher pain intensity (aOR 2.04; 95% CI 1.02-4.07). The odds of PGP were highest for women with GJH and BMI ≥25 kg/m2 (aOR 6.88; 95% CI 1.34-35.27) compared with women with normal joint mobility and BMI <25 kg/m2 . The estimated associations were weaker and not statistically significant in late pregnancy or after childbirth.Conclusions: Women with GJH did not have an increased risk of PGP during or after pregnancy but reported higher pain intensity in early pregnancy compared with women with normal joint mobility. Since women with combined GJH and BMI ≥25 kg/m2 had the highest odds of PGP in early pregnancy, our results may suggest that health care needs to pay attention to and develop methods to reduce the risk of PGP and delay the onset of pain during pregnancy in women with this combination.Keywords: Uppsala pelvic pain study; body mass index; generalized joint hypermobility; pelvic girdle pain; pregnancy.
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| 5. |
- Alim, Abdul, 1983-, et al.
(författare)
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Do Mast Cells Have a Role in Tendon Healing and Inflammation?
- 2020
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 9:5
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Forskningsöversikt (refereegranskat)abstract
- Understanding the links between the tendon healing process, inflammatory mechanisms, and tendon homeostasis/pain after tissue damage is crucial in developing novel therapeutics for human tendon disorders. The inflammatory mechanisms that are operative in response to tendon injury are not fully understood, but it has been suggested that inflammation occurring in response to nerve signaling, i.e., neurogenic inflammation, has a pathogenic role. The mechanisms driving such neurogenic inflammation are presently not clear. However, it has recently been demonstrated that mast cells present within the injured tendon can express glutamate receptors, raising the possibility that mast cells may be sensitive to glutamate signaling and thereby modulate neurogenic inflammation following tissue injury. In this review, we discuss the role of mast cells in the communication with peripheral nerves, and their emerging role in tendon healing and inflammation after injury.
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| 6. |
- Alim, Abdul, 1983-, et al.
(författare)
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Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells
- 2021
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Ingår i: Cellular & Molecular Immunology. - : Springer Nature. - 1672-7681 .- 2042-0226. ; 18:10, s. 2383-2392
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Tidskriftsartikel (refereegranskat)abstract
- Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system. However, it is not clear the mechanism by which mast cells communicate with peripheral nerves. We previously found that mast cells located within healing tendons can express glutamate receptors, raising the possibility that mast cells may be sensitive to glutamate signaling. To evaluate this hypothesis, we stimulated primary mast cells with glutamate and showed that glutamate induced the profound upregulation of a panel of glutamate receptors of both the ionotropic type (NMDAR1, NMDAR2A, and NMDAR2B) and the metabotropic type (mGluR2 and mGluR7) at both the mRNA and protein levels. The binding of glutamate to glutamate receptors on the mast cell surface was confirmed. Further, glutamate had extensive effects on gene expression in the mast cells, including the upregulation of pro-inflammatory components such as IL-6 and CCL2. Glutamate also induced the upregulation of transcription factors, including Egr2, Egr3 and, in particular, FosB. The extensive induction of FosB was confirmed by immunofluorescence assessment. Glutamate receptor antagonists abrogated the responses of the mast cells to glutamate, supporting the supposition of a functional glutamate-glutamate receptor axis in mast cells. Finally, we provide in vivo evidence supporting a functional glutamate-glutamate receptor axis in the mast cells of injured tendons. Together, these findings establish glutamate as an effector of mast cell function, thereby introducing a novel principle for how cells in the immune system can communicate with nerve cells.
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| 7. |
- Alim, Abdul, 1983-
(författare)
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Mechanisms in Tendon Healing : Pain, Biomarkers and the Role of Mast Cells
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tendon injuries and tendinopathy are common disorders, but the underlying mechanisms are not well understood. The overall aim of this thesis was to better understand the mechanisms underlying tendon healing, pain, and inflammation.The aim of the first study was to assess biomarkers of tendon healing, including procollagen type I (PINP) and type III (PIIINP) in relation to patient outcome in 65 patients with Achilles tendon rupture (ATR). At two weeks post-ATR, PINP and PIIINP-levels were quantified using microdialysis followed by ELISA. At one-year post-ATR patient outcome was assessed using the validated Achilles tendon Total Rupture Score. We found that higher ratio of PINP and PIIINP to total protein were significantly associated with less pain but more fatigue in the affected limb.In the second study, we applied Intermittent Pneumatic Compression (IPC) therapy for two weeks to stimulate tendon healing. The patients received either adjuvant IPC treatment or treatment-as-usual in a plaster cast without IPC. We observed that IPC therapy significantly increased PINP levels in the injured tendon, suggesting enhanced healing response.In our third study, we investigated healing response and the role of mast cells (MCs) in-vivo using an ATR rat model. Three weeks postoperatively, we demonstrated an increased number of MCs and a higher proportion of degranulated MCs in the injured tendon compared to the control. We further established that MCs in the injured tendon were positive for the glutamate receptor NMDAR1.In our final study, we assessed the effect of glutamate stimulation on in-vitro-derived mouse bone marrow MCs. Mast cell degranulation was quantified through β-hexosaminidase release, immunofluorescence was used to quantify NMDARs at the protein level, and RT-qPCR/microarray was used to study the expression of NMDARs and associated genes. Glutamate induced a robust upregulation of glutamate receptors of both ionotropic and metabotropic type, both at the mRNA and at protein level. NMDAR1 co-localized with glutamate in the membrane of MCs, thereby confirming an interaction between glutamate and its receptor. Glutamate also induced expression of pro-inflammatory compounds such as IL-6 and CCL2 and transcription factors such as Egr2, Egr3 and FosB. Moreover, the NMDA-channel blocker MK-801 completely abrogated the response of MCs to glutamate, supporting a functional glutamate–glutamate receptor axis in MCs.Together, findings presented in this dissertation reveal possible mechanisms of tendon healing in relation to pain and function, and establish a novel principle for how immune cells can communicate with nerve cells after ATR.
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| 8. |
- Alim, Md Abdul, et al.
(författare)
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Increased mast cell degranulation and co-localization of mast cells with the NMDA receptor-1 during healing after Achilles tendon rupture
- 2017
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Ingår i: Cell and Tissue Research. - Berlin Heidelberg : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 370:3, s. 451-460
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Tidskriftsartikel (refereegranskat)abstract
- The role of inflammation and the mechanism of tendon healing after rupture has historically been a matter of controversy. The purpose of the present study is to investigate the role of mast cells and their relation to the NMDA receptor-1 (a glutamate receptor) during healing after Achilles tendon rupture. Eight female Sprague Dawley rats had their right Achilles tendon transected. Three weeks after rupture, histological quantification of mast cell numbers and their state of degranulation was assessed by histochemistry. Co-localization of mast cell tryptase (a mast cell marker) and NMDA receptor-1 was determined by immunofluorescence. The intact left Achilles tendon was used as control. An increased number of mast cells and a higher proportion of degranulated mast cells were found in the healing Achilles tendon compared to the intact. In addition, increased co-localization of mast cell tryptase and NMDA receptor-1 was seen in the areas of myotendinous junction, mid-tendon proper and bone tendon junction of the healing versus the intact tendon. These findings introduce a possible role for mast cells in the healing phase after Achilles tendon rupture.
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| 9. |
- Bendrik, Regina
(författare)
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Aspects of improving and maintaining physical activity in patients with hip or knee osteoarthritis
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: This thesis aims to enhance knowledge of how people with osteoarthritis should be managed and supported in order to increase and maintain physical activity in the long-term. Method: Study I and study II was based on a randomised controlled study (RCT) including 141 osteoarthritis patients. The short and long-term effect of an individualised physical activity on prescription intervention compared with individualised advice about physical activity were evaluated. The primary outcome was physical activity and secondary outcomes were fitness/performance, pain and quality of life, evaluated at 6, 12 and 24 months. In Study III, 7-day diaries were evaluated regarding which forms of physical activity i.e. walking, swimming, cycling, gardening etc. the patients chose themselves and maintained after one and two years. In addition were evaluated, which category these activities belonged to: aerobic, muscle strength, mind-body or everyday activity, and whether there were differences in characteristic of the patients in the different forms. In study IV responsiveness of function, how well instruments captured an improvement, one year after a physical activity intervention was measured. Two unilateral performance-based tests were compared with a bilateral performance-based test and with questionnaires about function. Results: The RCT provided no evidence that individualised physical activity on prescription differ from individualised advice on physical activity in improving short and long-term physical activity, function, pain and quality of life (Study I and II). Walking was the form of physical activity performed most frequently and best maintained after 12 and 24 months. Walking were preferred by women, older individuals and individuals with weak legs while men also preferred everyday activity and cycling. Few patients preferred strength training (Study III). The maximal step-up test (one-leg testing) was more responsive to change in physical function (SMD effect size 0.57) compare to the bilateral 30-second chair-stand test (0.48) (Study IV). Conclusion: There is still absence of evidence for any particular physical activity intervention to effectively increase physical activity in the long-term in osteoarthritis patients. Individual counselling with support to choose preferred physical activities that are easy to perform in daily life may be a beneficial approach for long-term maintenance.
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| 10. |
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