| 1. |
- Ageberg, Eva, et al.
(författare)
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Effects of neuromuscular training (NEMEX-TJR) on patient-reported outcomes and physical function in severe primary hip or knee osteoarthritis: a controlled before-and-after study
- 2013
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: The benefits of exercise in mild and moderate knee or hip osteoarthritis (OA) are apparent, but the evidence in severe OA is less clear. We recently reported that neuromuscular training was well tolerated and feasible in patients with severe primary hip or knee OA. The aims of this controlled before-and-after study were to compare baseline status to an age-matched population-based reference group and to examine the effects of neuromuscular training on patient-reported outcomes and physical function in patients with severe primary OA of the hip or knee. Methods: 87 patients (60-77 years) with severe primary OA of the hip (n = 38, 55% women) or knee (n = 49, 59% women) awaiting total joint replacement (TJR) had supervised, neuromuscular training (NEMEX-TJR) in groups with individualized level and progression of training. A reference group (n = 43, 53% women) was included for comparison with patients' data. Assessments included self-reported outcomes (HOOS/KOOS) and measures of physical function (chair stands, number of knee bends/30 sec, knee extensor strength, 20-meter walk test) at baseline and at follow-up before TJR. Analysis of covariance (ANCOVA) was used for comparing patients and references and elucidating influence of demographic factors on change. The paired t-test was used for comparisons within groups. Results: At baseline, patients reported worse scores than the references in all HOOS/KOOS subscales (hip 27-47%, knee 14-52%, of reference scores, respectively) and had functional limitations (hip 72-85%, knee 42-85%, of references scores, respectively). NEMEX-TJR (mean 12 weeks (SD 5.6) of training) improved self-reported outcomes (hip 9-29%, knee 7-20%) and physical function (hip 3-18%, knee 5-19%) (p < 0.005). Between 42% and 62% of hip OA patients, and 39% and 61% of knee OA patients, displayed a clinically meaningful improvement (>= 15%) in HOOS/KOOS subscales by training. The improvement in HOOS/KOOS subscale ADL was greater for patients with knee OA than hip OA, while the improvement in subscale Sport/Rec was greater for patients with hip OA than knee OA. Conclusions: Both self-reported outcomes and physical function were clearly worse compared with the reference group. Neuromuscular training with an individualized approach and gradual progression showed promise for improving patient-reported outcomes and physical function even in older patients with severe primary OA of the hip or knee.
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| 2. |
- Berglund, Birgitta, et al.
(författare)
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Quantitative and qualitative perceptual analysis of cold dysesthesia and hyperalgesia in fibromyalgia.
- 2002
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 96:1-2, s. 177-87
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Tidskriftsartikel (refereegranskat)abstract
- Somatosensory perception thresholds, perceived intensity, and quality of perceptions were assessed in 20 women with fibromyalgia syndrome (FMS) and in 20 healthy age-matched female controls. All patients and controls scaled perceived intensity and described perceived quality of randomized thermal (Thermotest) and tactile (von Frey filaments) stimulation. Perceived intensity was scaled by free-number magnitude estimation and interindividual comparability was accomplished by Master Scaling. Perceived quality was assessed by choosing verbal descriptors from a list. Thenar was used as a reference for each modality tested. All patients were able to reliably scale perceived intensity at thenar, as well as in pain-affected body areas. Perception thresholds for cold pain, heat pain, cold-pain tolerance and heat-pain tolerance were significantly lower in patients than controls. For cold and tactile stimulation, the master scaled perceived intensities were significantly higher in patients' pain-affected areas, whereas for warmth/heat stimulation, the intensities were significantly lower. In the qualitative perceptual analysis the most striking and significant finding was the aberration of cold-evoked perceptions in all patients: most stimuli in the range of 30-10 degrees C were reported as heat or other paresthetic or dysesthetic perceptions. The perceptual quality of warmth, and of touch, did not differ from the controls. Another aberration was observed in the nociceptive range of thermal and of tactile stimulation as significantly more frequent pain-related descriptors than in controls. This indicates a general nociceptive facilitation in addition to the lower thermal pain thresholds. The combination of cold hyperesthesia, cold dysesthesia, and multimodal hyperalgesia suggests a selective pathophysiology at a particular level of integration, possibly in the insular cortex. It is suggested that the aberrations revealed by the supraliminal sensory evaluation may be generic for FMS. Particularly, the aberrations established in all patients for perceived quality and intensity in the cold sensory channel may be an additional diagnostic criterion.
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| 3. |
- Flodin, Pär, et al.
(författare)
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Intrinsic Brain Connectivity in Chronic Pain : A Resting-State fMRI Study in Patients with Rheumatoid Arthritis.
- 2016
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Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media SA. - 1662-5161. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rheumatoid arthritis (RA) is commonly accompanied by pain that is discordant with the degree of peripheral pathology. Very little is known about the cerebral processes involved in pain processing in RA. Here we investigated resting-state brain connectivity associated with prolonged pain in RA.METHODS: 24 RA subjects and 19 matched controls were compared with regard to both behavioral measures of pain perception and resting-resting state fMRI data acquired subsequently to fMRI sessions involving pain stimuli. The resting-state fMRI brain connectivity was investigated using 159 seed regions located in cardinal pain processing brain regions. Additional principal component based multivariate pattern analysis of the whole brain connectivity pattern was carried out in a data driven analysis to localize group differences in functional connectivity.RESULTS: When RA patients were compared to controls, we observed significantly lower pain resilience for pressure on the affected finger joints (i.e., P50-joint) and an overall heightened level of perceived global pain in RA patients. Relative to controls, RA patients displayed increased brain connectivity predominately for the supplementary motor areas, mid-cingulate cortex, and the primary sensorimotor cortex. Additionally, we observed an increase in brain connectivity between the insula and prefrontal cortex as well as between anterior cingulate cortex and occipital areas for RA patients. None of the group differences in brain connectivity were significantly correlated with behavioral parameters.CONCLUSION: Our study provides experimental evidence of increased connectivity between frontal midline regions that are implicated in affective pain processing and bilateral sensorimotor regions in RA patients.
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| 4. |
- Jacquot, F., et al.
(författare)
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Lysophophatidylcholine 16:0 mediates chronic joint pain associated to rheumatic diseases through acid-sensing ion channel 3
- 2022
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Ingår i: Pain. - : International Association for the Study of Pain. - 0304-3959 .- 1872-6623. ; 163:10, s. 1999-2013
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatic diseases are often associated to debilitating chronic pain, which remains difficult to treat and requires new therapeutic strategies. We had previously identified lysophosphatidylcholine (LPC) in the synovial fluids from few patients and shown its effect as a positive modulator of acid-sensing ion channel 3 (ASIC3) able to induce acute cutaneous pain in rodents. However, the possible involvement of LPC in chronic joint pain remained completely unknown. Here, we show, from 2 independent cohorts of patients with painful rheumatic diseases, that the synovial fluid levels of LPC are significantly elevated, especially the LPC16:0 species, compared with postmortem control subjects. Moreover, LPC16:0 levels correlated with pain outcomes in a cohort of osteoarthritis patients. However, LPC16:0 do not appear to be the hallmark of a particular joint disease because similar levels are found in the synovial fluids of a second cohort of patients with various rheumatic diseases. The mechanism of action was next explored by developing a pathology-derived rodent model. Intra-articular injections of LPC16:0 is a triggering factor of chronic joint pain in both male and female mice, ultimately leading to persistent pain and anxiety-like behaviors. All these effects are dependent on ASIC3 channels, which drive sufficient peripheral inputs to generate spinal sensitization processes. This study brings evidences from mouse and human supporting a role for LPC16:0 via ASIC3 channels in chronic pain arising from joints, with potential implications for pain management in osteoarthritis and possibly across other rheumatic diseases.
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| 5. |
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| 6. |
- Nijs, Jo, et al.
(författare)
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Central sensitisation in chronic pain conditions : latest discoveries and their potential for precision medicine
- 2021
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Ingår i: The Lancet Rheumatology. - : Elsevier. - 2665-9913. ; 3:5, s. E383-E392
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Forskningsöversikt (refereegranskat)abstract
- Chronic pain is a leading cause of disability globally and associated with enormous health-care costs. The discrepancy between the extent of tissue damage and the magnitude of pain, disability, and associated symptoms represents a diagnostic challenge for rheumatology specialists. Central sensitisation, defined as an amplification of neural signalling within the CNS that elicits pain hypersensitivity, has been investigated as a reason for this discrepancy. Features of central sensitisation have been documented in various pain conditions common in rheumatology practice, including fibromyalgia, osteoarthritis, rheumatoid arthritis, Ehlers-Danlos syndrome, upper extremity tendinopathies, headache, and spinal pain. Within individual pain conditions, there is substantial variation among patients in terms of presence and magnitude of central sensitisation, stressing the importance of individual assessment. Central sensitisation predicts poor treatment outcomes in multiple patient populations. The available evidence supports various pharmacological and non-pharmacological strategies to reduce central sensitisation and to improve patient outcomes in several conditions commonly seen in rheumatology practice. These data open up new treatment perspectives, with the possibility for precision pain medicine treatment according to pain phenotyping as a logical next step. With this view, studies suggest the possibility of matching non-pharmacological approaches, or medications, or both to the central sensitisation pain
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| 7. |
- Nijs, Jo, et al.
(författare)
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Nociceptive, neuropathic, or nociplastic low back pain? : The low back pain phenotyping (BACPAP) consortium's international and multidisciplinary consensus recommendations
- 2024
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Ingår i: The Lancet Rheumatology. - : Elsevier. - 2665-9913. ; 6:3, s. e178-e188
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Tidskriftsartikel (refereegranskat)abstract
- The potential to classify low back pain as being characterised by dominant nociceptive, neuropathic, or nociplastic mechanisms is a clinically relevant issue. Preliminary evidence suggests that these low back pain phenotypes might respond differently to treatments; however, more research must be done before making specific recommendations. Accordingly, the low back pain phenotyping (BACPAP) consortium was established as a group of 36 clinicians and researchers from 13 countries (five continents) and 29 institutions, to apply a modified Nominal Group Technique methodology to develop international and multidisciplinary consensus recommendations to provide guidance for identifying the dominant pain phenotype in patients with low back pain, and potentially adapt pain management strategies. The BACPAP consortium's recommendations are also intended to provide direction for future clinical research by building on the established clinical criteria for neuropathic and nociplastic pain. The BACPAP consortium's consensus recommendations are a necessary early step in the process to determine if personalised pain medicine based on pain phenotypes is feasible for low back pain management. Therefore, these recommendations are not ready to be implemented in clinical practice until additional evidence is generated that is specific to these low back pain phenotypes.
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| 8. |
- Palada, Vinko, et al.
(författare)
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Elevated inflammatory proteins in cerebrospinal fluid from patients with painful knee osteoarthritis are associated with reduced symptom severity
- 2020
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Ingår i: Journal of Neuroimmunology. - : ELSEVIER. - 0165-5728 .- 1872-8421. ; 349
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Tidskriftsartikel (refereegranskat)abstract
- Neuroinflammation and periphery-to-CNS neuroimmune cross-talk in patients with painful knee osteoarthritis (OA) are poorly understood. We utilized proximity extension assay to measure the level of 91 inflammatory proteins in CSF and serum from OA patients and controls. The patients had elevated levels of 48 proteins in CSF indicating neuroinflammation. Ten proteins were correlated between CSF and serum and potentially involved in periphery-to-CNS neuroimmune cross-talk. Seven CSF proteins, all with previously reported neuroprotective effects, were associated with lower pain intensity and milder knee-related symptoms. Our findings indicate that neuroinflammation in OA could be protective and associated with less severe symptoms.
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| 9. |
- Ahmed, Aisha S., et al.
(författare)
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Activation of NF-kappa B in Synovium versus Cartilage from Patients with Advanced Knee Osteoarthritis : A Potential Contributor to Inflammatory Aspects of Disease Progression
- 2018
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Ingår i: Journal of Immunology. - : AMER ASSOC IMMUNOLOGISTS. - 0022-1767 .- 1550-6606. ; 201:7, s. 1918-1927
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to assess the activation and association of the NF-kappa B system across synovial membrane (SM) and articular cartilage (AC) in patients with knee osteoarthritis (OA) and ascertain its potential effects on catabolic mediator expression in advanced OA. SM and AC were obtained from 40 OA patients undergoing total knee arthroplasty and from 19 postmortem control subjects. NF-kappa B subunit RelA in nuclear and cytosolic fractions and NF-kappa B1-DNA binding in nuclear extracts was assessed by ELISA, whereas NFKB1, RELA, IL-8, IL-6, and MMP3 gene expression were analyzed by reverse transcriptase-quantitative PCR in tissues. We observed higher SM nuclear RelA protein levels and upregulated NF-kappa B1-DNA binding in OA patients compared with postmortem controls. However, in AC, lower nuclear RelA levels were observed compared with cytosolic extracts in patients. Nuclear RelA levels correlated positively with NF-kappa B1-DNA binding in SM and AC in patients. SM RELA and MMP3 mRNA levels were upregulated, whereas IL-8 and IL-6 as well as AC RELA were downregulated in patients compared with controls. In SM, nuclear RelA levels correlated positively with MMP3 gene expression in patients. A negative correlation was observed between SM nuclear RelA levels and AC NF-kappa B1-DNA binding, and SM nuclear NF-kappa B1-DNA binding correlated negatively with AC MMP3 and NFKB1 mRNA levels in patients. These findings highlight NF-kappa B-triggered cross-talk and feedback mechanisms between SM and AC in OA. Further, our findings strongly support a role for an activated NF-kappa B system in the transcriptional mechanism of inflammatory processes, especially in SM of patients with advanced OA.
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| 10. |
- Ahmed, Aisha S, et al.
(författare)
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NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease.
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- The role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) has been highlighted in mechanisms underlying inflammatory and neuropathic pain processes. The present study was designed to investigate whether NF-κB signaling is associated with pain-related neuropeptide expression in patients with chronic back pain related to degenerative disc disease (DDD). Intervertebral disc (IVD) tissues were collected from forty DDD patients undergoing disc replacement or fusion surgery, and from eighteen postmortem (PM) control subjects. RELA, NFKB1, CGRP, TAC1, TRPV1, and MMP-3 gene expression were analyzed by RT-qPCR, while NF-κB subunit RelA and NF-κB1⁻DNA binding in nuclear extracts and calcitonin gene related peptide (CGRP), substance P (SP), and transient receptor potential, subfamily V, member 1 (TRPV1) protein levels in cytosolic extracts of tissues were assessed by enzyme-linked immunosorbent assay (ELISA). An upregulated NF-κB1⁻DNA binding, and higher CGRP and TRPV1 protein levels were observed in DDD patients compared to PM controls. In DDD patients, NF-κB1⁻DNA binding was positively correlated with nuclear RelA levels. Moreover, NF-κB1⁻DNA binding was positively associated with TRPV1 and MMP-3 gene and SP and TRPV1 protein expression in DDD patients. Our results indicate that the expression of SP and TRPV1 in IVD tissues was associated with NF-κB activation. Moreover, NF-κB may be involved in the generation or maintenance of peripheral pain mechanisms by the regulation of pain-related neuropeptide expression in DDD patients.
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