Neuroimmune interactions may contribute to severe pain and regional inflammatory and autonomic signs in complex regional pain syndrome (CRPS), a posttraumatic pain disorder. Here, we investigated ...peripheral and central immune mechanisms in a translational passive transfer trauma mouse model of CRPS. Small plantar skin–muscle incision was performed in female C57BL/6 mice treated daily with purified serum immunoglobulin G (IgG) from patients with longstanding CRPS or healthy volunteers followed by assessment of paw edema, hyperalgesia, inflammation, and central glial activation. CRPS IgG significantly increased and prolonged swelling and induced stable hyperalgesia of the incised paw compared with IgG from healthy controls. After a short-lasting paw inflammatory response in all groups, CRPS IgG-injected mice displayed sustained, profound microglia and astrocyte activation in the dorsal horn of the spinal cord and pain-related brain regions, indicating central sensitization. Genetic deletion of interleukin-1 (IL-1) using IL-1αβ knockout (KO) mice and perioperative IL-1 receptor type 1 (IL-1R1) blockade with the drug anakinra, but not treatment with the glucocorticoid prednisolone, prevented these changes. Anakinra treatment also reversed the established sensitization phenotypewhen initiated 8 days after incision. Furthermore, with the generation of an IL-1β floxed(fl/fl) mouse line, we demonstrated that CRPS IgG-induced changes are in part mediated by microglia-derived IL-1β, suggesting that both peripheral and central inflammatory mechanisms contribute to the transferred disease phenotype. These results indicate that persistent CRPS is often contributed to by autoantibodies and highlight a potential therapeutic use for clinically licensed antagonists, such as anakinra, to prevent or treat CRPS via blocking IL-1 actions.
Abstract
Chronic fatigue syndrome, postural orthostatic tachycardia syndrome, complex regional pain syndrome and silicone implant incompatibility syndrome are a subject of debate among clinicians and ...researchers. Both the pathogenesis and treatment of these disorders require further study. In this paper we summarize the evidence regarding the role of autoimmunity in these four syndromes with respect to immunogenetics, autoimmune co-morbidities, alteration in immune cell subsets, production of autoantibodies and presentation in animal models. These syndromes could be incorporated in a new concept of autoimmune neurosensory dysautonomia with the common denominators of autoantibodies against G-protein coupled receptors and small fiber neuropathy. Sjogren's syndrome, which is a classical autoimmune disease, could serve as a disease model, illustrating the concept. Development of this concept aims to identify an apparently autoimmune subgroup of the disputable disorders, addressed in the review, which may most benefit from the immunotherapy.
•Autoimmune aspects of CFS, POTS, CRPS and SIIS are discussed.•The common denominators of anti-GPCR AAb and SFN are identified for these syndromes.•A new concept of autoimmune neurosensory dysautonomia is suggested.•Sjogren's syndrome can illustrate the suggested concept.
Matrix metalloproteinases (MMP)-2 and MMP-9 play important roles in inflammation as well as in pain processes. For this reason, we compared the concentrations of these enzymes in skin and serum of ...patients with complex regional pain syndrome (CRPS), other pain diseases and healthy subjects. We analyzed ipsi- and contralateral skin biopsies of 18 CRPS patients, as well as in 10 pain controls and 9 healthy subjects. Serum samples were analyzed from 20 CRPS, 17 pain controls and 17 healthy subjects. All samples were analyzed with ELISA. Concentrations were then compared to clinical data as well as to quantitative sensory testing data.MMP-2 was increased in both ipsi- and contralateral skin biopsies of CRPS patients compared to healthy subjects. While low ipsilateral MMP-2 was associated with trophic changes, contralateral MMP-2 inversely correlated with the CRPS severity. MMP-9 was also locally increased in ipsilateral CRPS skin, and higher ipsi- and contralateral MMP-9 levels correlated with CRPS severity. We conclude that MMP-2 and MMP-9 are differently expressed depending on the clinical phenotype in CRPS. PERSPECTIVE: This article describes an upregulation of MMPs in CRPS and pain controls and shows different expression of MMP-2 and -9 depending on clinical phenotype in CRPS. These results provide evidence that MMP-2 and -9 play a key role in CRPS pathophysiology.
Abstract Background The aims of this study were to determine the prevalence and incidence of patellofemoral pain (PFP) in young female athletes and prospectively evaluate measures of frontal plane ...knee loading during landing to determine their relationship to development of PFP. We hypothesized that increased dynamic knee abduction measured during preseason biomechanical testing would be increased in those who developed PFP relative to teammates who did not develop PFP. Methods Middle and high school female athletes ( n = 240) were evaluated by a physician for PFP and for landing biomechanics prior to their basketball season. The athletes were monitored for athletic exposures and PFP injury during their competitive seasons. Findings At the beginning of the season, the point prevalence of PFP was 16.3 per 100 athletes. The cumulative incidence risk and rate for the development of new unilateral PFP was 9.66 per 100 athletes and 1.09 per 1000 athletic exposures, respectively. All new PFPs developed in middle school athletes who demonstrated mean International Knee Documentation Committee score of 85.6 ± 7.7 at diagnosis. The new PFP group demonstrated increased knee abduction moments at initial contact (95% CI: 0.32 to 4.62 N m) on the most-symptomatic limb and maximum (95% CI: 1.3 to 10.1 N m; P = 0.02) on the least-symptomatic (or no symptoms) limb relative to the matched control limbs. Knee abduction moments remained increased in the new PFP group when normalized to body mass ( P < 0.05). Interpretation The increased knee abduction landing mechanics in the new PFP group indicate that frontal plane loads contribute to increased incidence of PFP.
Background:
The prevalence of adolescent knee pain is 33%, and patellofemoral pain (PFP) is the most common diagnosis with a nontraumatic onset. The 2-year prognosis of adolescent PFP compared with ...other types of knee pain is unknown.
Purpose:
To investigate the 2-year prognosis of knee pain among adolescents with and without a diagnosis of PFP.
Study Design:
Cohort study; Level of evidence, 2.
Methods:
In 2011, a cohort of 2200 adolescents aged 15 to 19 years answered an online questionnaire on musculoskeletal pain. Of these, 504 reported knee pain, and 153 of these were clinically diagnosed with PFP. After 2 years, the 504 adolescents, as well as 252 randomly selected adolescents who did not report knee pain in 2011, were contacted again. Primary outcome at follow-up was the proportion of adolescents with knee pain during the last week prior to follow-up.
Results:
Overall, 55.9% (95% CI, 50.8%-60.9%) of those reporting knee pain at baseline also reported pain 2 years later. Adolescents diagnosed with PFP had a 1.26 (95% CI, 1.05-1.50) higher relative risk (RR) of knee pain at follow-up compared with other types of knee pain. Adolescents with PFP were significantly more likely to reduce or stop sports participation compared with adolescents with other types of knee pain. Of those without knee pain at baseline, 12.8% (95% CI, 8.4%-17.2%) reported knee pain at follow-up in 2013. Adolescents with knee pain at baseline had a 4.51 (95% CI, 3.15-6.45) higher RR of knee pain at follow-up compared with adolescents without knee pain at baseline.
Conclusion:
Knee pain during adolescence, and PFP in particular, is in most cases present after 2 years and thus may not be self-limiting. A greater focus on early detection and prevention of knee pain during adolescence is needed.
Study Design Systematic review with meta-analysis. Background The addition of hip strengthening to knee strengthening for persons with patellofemoral pain has the potential to optimize treatment ...effects. There is a need to systematically review and pool the current evidence in this area. Objective To examine the efficacy of hip strengthening, associated or not with knee strengthening, to increase strength, reduce pain, and improve activity in individuals with patellofemoral pain. Methods A systematic review of randomized and/or controlled trials was performed. Participants in the reviewed studies were individuals with patellofemoral pain, and the experimental intervention was hip and knee strengthening. Outcome data related to muscle strength, pain, and activity were extracted from the eligible trials and combined in a meta-analysis. Results The review included 14 trials involving 673 participants. Random-effects meta-analyses revealed that hip and knee strengthening decreased pain (mean difference, -3.3; 95% confidence interval CI: -5.6, -1.1) and improved activity (standardized mean difference, 1.4; 95% CI: 0.03, 2.8) compared to no training/placebo. In addition, hip and knee strengthening was superior to knee strengthening alone for decreasing pain (mean difference, -1.5; 95% CI: -2.3, -0.8) and improving activity (standardized mean difference, 0.7; 95% CI: 0.2, 1.3). Results were maintained beyond the intervention period. Meta-analyses showed no significant changes in strength for any of the interventions. Conclusion Hip and knee strengthening is effective and superior to knee strengthening alone for decreasing pain and improving activity in persons with patellofemoral pain; however, these outcomes were achieved without a concurrent change in strength. Level of Evidence Therapy, level 1a-. J Orthop Sports Phys Ther 2018;48(1):19-31. Epub 15 Oct 2017. doi:10.2519/jospt.2018.7365.
Management of chronic pelvic pain (CPP) remains a huge challenge for care providers and a major burden for healthcare systems. Treating chronic pain that has no obvious cause warrants an ...understanding of the difficulties in managing these conditions. Chronic pain has recently been accepted as a disease in its own right by the World Health Organization, with chronic pain without obvious cause being classified as chronic primary pain. Despite innumerable treatments that have been proposed and tried to date for CPP, unimodal therapeutic options are mostly unsuccessful, especially in unselected individuals. In contrast, individualised multimodal management of CPP seems the most promising approach and may lead to an acceptable situation for a large proportion of patients. In the present review, the interdisciplinary and interprofessional European Association of Urology Chronic Pelvic Pain Guideline Group gives a contemporary overview of the most important concepts to successfully diagnose and treat this challenging disease.
Evaluation and Treatment of Knee Pain: A Review Duong, Vicky; Oo, Win Min; Ding, Changhai ...
JAMA : the journal of the American Medical Association,
10/2023, Letnik:
330, Številka:
16
Journal Article
Recenzirano
IMPORTANCE: Approximately 5% of all primary care visits in adults are related to knee pain. Osteoarthritis (OA), patellofemoral pain, and meniscal tears are among the most common causes of knee pain. ...OBSERVATIONS: Knee OA, affecting an estimated 654 million people worldwide, is the most likely diagnosis of knee pain in patients aged 45 years or older who present with activity-related knee joint pain with no or less than 30 minutes of morning stiffness (95% sensitivity; 69% specificity). Patellofemoral pain typically affects people younger than 40 years who are physically active and has a lifetime prevalence of approximately 25%. The presence of anterior knee pain during a squat is approximately 91% sensitive and 50% specific for patellofemoral pain. Meniscal tears affect an estimated 12% of the adult population and can occur following acute trauma (eg, twisting injury) in people younger than 40 years. Alternatively, a meniscal tear may be a degenerative condition present in patients with knee OA who are aged 40 years or older. The McMurray test, consisting of concurrent knee rotation (internal or external to test lateral or medial meniscus, respectively) and extension (61% sensitivity; 84% specificity), and joint line tenderness (83% sensitivity; 83% specificity) assist diagnosis of meniscal tears. Radiographic imaging of all patients with possible knee OA is not recommended. First-line management of OA comprises exercise therapy, weight loss (if overweight), education, and self-management programs to empower patients to better manage their condition. Surgical referral for knee joint replacement can be considered for patients with end-stage OA (ie, no or minimal joint space with inability to cope with pain) after using all appropriate conservative options. For patellofemoral pain, hip and knee strengthening exercises in combination with foot orthoses or patellar taping are recommended, with no indication for surgery. Conservative management (exercise therapy for 4-6 weeks) is also appropriate for most meniscal tears. For severe traumatic (eg, bucket-handle) tears, consisting of displaced meniscal tissue, surgery is likely required. For degenerative meniscal tears, exercise therapy is first-line treatment; surgery is not indicated even in the presence of mechanical symptoms (eg, locking, catching). CONCLUSIONS AND RELEVANCE: Knee OA, patellofemoral pain, and meniscal tears are common causes of knee pain, can be diagnosed clinically, and can be associated with significant disability. First-line treatment for each condition consists of conservative management, with a focus on exercise, education, and self-management.
Animal and human studies indicate that electrical stimulation of dorsal root ganglion (DRG) neurons may modulate neuropathic pain signals. ACCURATE, a pivotal, prospective, multicenter, randomized ...comparative effectiveness trial, was conducted in 152 subjects diagnosed with complex regional pain syndrome or causalgia in the lower extremities. Subjects received neurostimulation of the DRG or dorsal column (spinal cord stimulation, SCS). The primary end point was a composite of safety and efficacy at 3 months, and subjects were assessed through 12 months for long-term outcomes and adverse events. The predefined primary composite end point of treatment success was met for subjects with a permanent implant who reported 50% or greater decrease in visual analog scale score from preimplant baseline and who did not report any stimulation-related neurological deficits. No subjects reported stimulation-related neurological deficits. The percentage of subjects receiving ≥50% pain relief and treatment success was greater in the DRG arm (81.2%) than in the SCS arm (55.7%, P < 0.001) at 3 months. Device-related and serious adverse events were not different between the 2 groups. Dorsal root ganglion stimulation also demonstrated greater improvements in quality of life and psychological disposition. Finally, subjects using DRG stimulation reported less postural variation in paresthesia (P < 0.001) and reduced extraneous stimulation in nonpainful areas (P = 0.014), indicating DRG stimulation provided more targeted therapy to painful parts of the lower extremities. As the largest prospective, randomized comparative effectiveness trial to date, the results show that DRG stimulation provided a higher rate of treatment success with less postural variation in paresthesia intensity compared to SCS.
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