Materiały źródłowe

• #1 Adhesive Capsulitis (Frozen Shoulder) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK532955/

  Adhesive capsulitis, commonly known as frozen shoulder, is characterized by painful and progressive shoulder motion loss due to fibrotic joint capsule changes. […] Despite its commonality, the pathophysiology remains only partially understood, and the condition is often under-recognized, leading to delays in treatment and prolonged disability. The persistent nature of adhesive capsulitis and its significant effect on a patient’s daily functioning emphasizes the critical need for expedient diagnosis, treatment, and a comprehensive care strategy involving multiple medical specialties. […] The pathophysiology of adhesive capsulitis remains uncertain and involves a complex interplay between inflammation and fibrosis. Initially, an inflammatory response leads to pain and limited motion. […] Subsequently, fibrotic changes occur within the joint capsule, particularly the rotator interval, leading to thickening of the coracohumeral ligament and contraction of the joint capsule.

• #1 Adhesive Capsulitis (Frozen Shoulder) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK532955/

  The fibrotic process is mediated by various cytokines and growth factors, which contribute to the proliferation of fibroblasts and excessive collagen deposition, further restricting shoulder mobility. […] Histologically, adhesive capsulitis is characterized by synovial hyperplasia, angiogenesis, and eventual joint capsule fibrosis. […] The pathophysiology involves both inflammation and fibrosis, and the condition passes through several stages, including an initial inflammatory phase, a fibrotic phase characterized by increasing stiffness and limited range of motion, and a thawing or regression phase, where gradual improvement in shoulder mobility occurs.

• #1 Adhesive Capsulitis (Frozen Shoulder): Practice Essentials, Problem, Epidemiology

  https://emedicine.medscape.com/article/1261598-overview

  Immune, inflammatory and fibrotic changes appear to be involved in the pathophysiology of FSS. The current hypothesis posits inflammation in the joint capsule followed by development of adhesions and fibrosis of the synovial lining. Thickening and contraction of the glenohumeral joint capsule and formation of collagenous tissue surrounding the joint reduces joint volume. […] Biomarkers in synovial fluid suggest chronic inflammation is present. The following markers have been identified in FSS: Intercellular adhesion molecule1 (ICAM-1; CD54), Transforming growth factorbeta (TGF-), Tumor necrosis factoralpha (TNF-), Interleukin-1 (IL-1) alpha and beta, IL-6, Platelet-derived growth factor (PDGF). […] Following the synovial inflammatory process, a high number of fibroblasts and myofibroblasts suggest a fibrotic process in the capsule. The condition is thought to result from progressive fibrosis and eventual contracture of the capsule of the glenohumeral joint, which causes pain and stiffness.

• #1 Atypical progress of frozen shoulder after COVID-19 vaccination: A case report

  https://www.wjgnet.com/2307-8960/full/v11/i15/3637.htm

  Moreover, cytokines such as the Alarmins high mobility group box 1 (HMGB1) are associated with pain in the frozen shoulder and peripheral nerve ingrowth. […] The exact cause of pain is unclear although the clinical symptoms and diagnostic workup in our case suggest the possibility of an association between cytokines, such as HMGB1, and shoulder pathology.

• #1 Biological Aspect of Pathophysiology for Frozen Shoulder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5994312/

  It is fairly well understood that frozen shoulder involves several stages, which reflect the series of process from capsular inflammation and fibrosis to spontaneous resolution of this fibrosis. […] However, the underlying pathophysiologic process remains poorly determined. […] Determining the pathophysiological processes of frozen shoulder is a pivotal milestone in the development of novel treatment for patients with frozen shoulder. […] Although articles for the pathophysiology of frozen shoulder provide inconsistent and inconclusive results, they have suggested both inflammation and fibrosis mediated by cytokines, growth factors, matrix metalloproteinases, and immune cells. […] Proinflammatory cytokines and growth factors released from immune cells control the action of fibroblast and matrix remodeling is regulated by the matrix metalloproteinases and their inhibitors.

• #1 The puzzling pathophysiology of frozen shoulders – a scoping review | Journal of Experimental Orthopaedics | Full Text

  https://jeo-esska.springeropen.com/articles/10.1186/s40634-020-00307-w

  Cytokines can regulate proliferation, activation and differentiation of fibroblasts, hereby dysregulating collagen synthesis. […] The mechanism of tissue fibrosis involves an imbalance in extracellular matrix turnover. […] The fibrotic effects of increased TIMP activity came to light when twelve patients were treated with Marimastat, a TIMP analogue for the treatment of gastric carcinoma. […] The MMP/TIMP ratio has been shown to be almost ten times lower in FS patients versus healthy controls. […] Transforming growth factor- one (TGF-1), and mechanical stress are two important factors contributing to contractility of fibroblasts. […] TGF-1 has been shown to stimulate contractility of fibroblasts in-vitro collagen gels and can be seen as a potent activator of myofibroblasts. […] Chronic low-grade inflammation might predispose to the development of FS.

• #1 The puzzling pathophysiology of frozen shoulders – a scoping review | Journal of Experimental Orthopaedics | Full Text

  https://jeo-esska.springeropen.com/articles/10.1186/s40634-020-00307-w

  Several authors have hypothesized an association with a chronic state of low grade inflammation which might predispose to the development of FS. […] An increasing amount of evidence supports a chronic state of low-grade inflammation as an important predisposing factor for the development of FS. […] The complexity of the pathophysiology of FS is outlined in this review. A state of low grade inflammation, as is associated with DM, cardiovascular disease and thyroid disorders, predisposes for the development of FS. An early immune response with elevated levels of alarmins such as HMGB1 and binding to the receptor of AGE starts the cascade of inflammation. Activation of the NF-B pathway together with mechanical stress stimulates release of inflammatory cytokines, of which TGF- has a prominent role. Fibroblasts proliferate, become activated and differentiate into myofibroblasts. This results in an imbalance of ECM turnover and a stiff and thickened glenohumeral capsule with abundance of type III collagen.

• #1 Frozen Shoulder – Physio Guide to Pathophysiology & Evidence Based Treatment – Bradley Physio

  https://www.bradleyphysio.co.uk/frozen-shoulder-physio-guide-to-pathophysiology-evidence-based-treatment

  We now know that frozen shoulder, is a painful inflammatory disorder with progressive fibrosis of the shoulder capsule but its pathogenesis is still unknown (Bak and Isaaksson, 2019). […] Due to the variety and conflicting evidence over the years stemming from the varying definitions of frozen shoulder, Lewis (2015), compiled a summary of abnormalities which were regularly seen in patients with frozen shoulder from 1952 through to 2009 yet there was still some uncertainty regarding the inflammatory changes. These were; […] Thickening and fibrosis of the rotator interval […] Scaring of the subscapular recess (between biceps and subscapularis tendons) […] Neovascularity […] Increased cytokine concentrations […] Contraction and fibrosis of the coracohumeral ligament […] Proliferation of fibroblasts and myofibroblasts […] Presence of contractile proteins.

• #1 Are Nerve Cells Involved in the Pathogenesis of Frozen Shoulder? – Sports Medicine Research

  https://www.sportsmedres.org/are-nerve-cells-involved-in/

  Idiopathic frozen shoulder (adhesive capsulitis) is a mysterious and misunderstood injury. It is characterized by decreases in both active and passive shoulder range of motion in addition to severe pain without any known origin. Recent research has found increased protein expression of growth factors and inflammatory mediators as well as increased nerve cells in the joint capsule. […] They found that the capsule tissue of frozen shoulder patients had hypercellularity (increased density of cells) and fibroblastic proliferation (associated with fibrosis) compared to controls. They also found that frozen shoulder patients had increased expression of nerve growth factor receptors as well as markers of blood vessels, nerves, and nerve growth factors compared to controls. This study is a large step in understanding the pathogenesis of idiopathic frozen shoulder. The results indicate that patients with idiopathic frozen shoulder have increased expression of several nerve and vascular proteins, which also correspond to tissue fibrosis. The increased nerve growth explains why frozen shoulder is very painful and the presence of vascular proteins suggests that an inflammatory response can very easily occur if the healthcare provider is too aggressive with joint mobilizations or range of motion exercises. […] These altered tissue properties may be the catalyst to the development of frozen shoulder.

• #1 Frozen Shoulder – Adhesive Capsulitis – OrthoInfo – AAOS

  https://orthoinfo.aaos.org/en/diseases–conditions/frozen-shoulder/

  Frozen shoulder, also called adhesive capsulitis, causes pain and stiffness in the shoulder. Over time, the shoulder becomes very hard to move. […] In frozen shoulder, the shoulder capsule thickens and becomes stiff and tight. Thick bands of tissue called adhesions develop. In many cases, there is less synovial fluid in the joint. […] The causes of frozen shoulder are not fully understood. There is no clear connection to arm dominance (the dominant arm is the arm you prefer to use for most tasks) or occupation. A few factors may put you more at risk for developing frozen shoulder. […] Frozen shoulder occurs much more often in people with diabetes. The reason for this is not known. In addition, diabetic patients with frozen shoulder tend to have a greater degree of stiffness that continues for a longer time before „thawing.”

• #1 Frozen shoulder (adhesive capsulitis) – UpToDate

  https://www.uptodate.com/contents/frozen-shoulder-adhesive-capsulitis

  Frozen shoulder can be primary (or idiopathic) but is often associated with other diseases and conditions. […] Patients with diabetes mellitus are at greater risk of developing frozen shoulder. In a meta-analysis of six case-control studies, diabetics were found to be over three times more likely to develop adhesive capsulitis, while the overall prevalence among diabetics is reported to be 10 to 20 percent. […] Prevalence among long-term diabetics may be even higher. A cross-sectional study reported the point prevalence of frozen shoulder in patients with long-lasting type 1 diabetes to be as high as 59 percent, with a lifetime prevalence 76 percent.

• #1 Adhesive Capsulitis (Frozen Shoulder): Practice Essentials, Problem, Epidemiology

  https://emedicine.medscape.com/article/1261598-overview

  Microvascular diseases such as diabetes mellitus may cause abnormal collagen repair, which predisposes patients to FSS. Increased glycosylation of collagen protein and increased formation of abnormal glycation end products and their subsequent accumulation have a detrimental effect on cellular and extracellular processes that might facilitate adhesion and fibrosis. Neovascularization with vascular endothelial growth factor (VEGF) staining has also been identified in diabetic tissue samples.

• #1 Frozen shoulder – etiology, pathogenesis and natural course | ShoulderDoc

  https://www.shoulderdoc.co.uk/news/view/627

  The term frozen shoulder (FS) is used to describe a clinical condition with restricted active and passive range of motion in all directions, both flexion, abduction and rotation. […] Different theories and speculations in aetiology started to be published. DePalma (1952) discussed the possibility of muscular inactivity to be the main course for the development of FS. […] The problem of identifying the true etiology arises when we look at primary frozen shoulder. Today, no comprehensive etiological model exists! […] The association with metabolic diseases is most well known regarding diabetes mellitus (both insulin-dependent and non-insulin-dependent types), especially retinopathy, but exists also with hypo- and hyperthyroidism. […] Pathoanatomically there is an involvement of the capsule in the glenohumeral joint. The capsule volume is reduced and this is the cause for the restricted range of motion.

• #1 Understanding Causes And Symptoms Of Frozen Shoulder

  https://centenoschultz.com/condition/frozen-shoulder/

  Natural degeneration: Degeneration of the tendons and the capsule can attract inflammatory cells. This can make the capsule stiff and lead to a frozen shoulder. […] In diabetes, studies show that higher levels of glycated hemoglobin (HbA1c), advanced glycation end products (AGEs), vascular endothelial growth factor (VEGF), interleukin-1 beta (IL-1) can cause changes in the rotator cuff tendons and increase capsular stiffness. This can cause adhesive capsulitis. […] Hyperthyroidism is an autoimmune condition in which the thyroid is highly active. Graves disease is an overactive thyroid disorder that results in high amounts of interleukin-2 (IL-2), interferon- (IFN-), and tumor necrosis factor- (TNF-) cytokines being secreted by Th1 cells, causing the production of fibroblast cells. […] These fibroblast cells lay down scar tissue which causes the joint capsule to stiffen, ultimately leading to a frozen shoulder.

• #1 Understanding Causes And Symptoms Of Frozen Shoulder

  https://centenoschultz.com/condition/frozen-shoulder/

  Hypothyroidism can also lead to frozen shoulder. This is because the thyroid hormones are involved in the synthesis and degeneration of collagen. […] When the thyroid hormones are imbalanced due to an underactive thyroid, it can dysregulate the synthesis and cell death of tendon cells. This can cause them to degenerate which can lead to a frozen shoulder. […] These cytokines can stimulate the production of scar tissue which can lead to a frozen shoulder. […] Tuberculosis can mimic the symptoms of and also cause a frozen shoulder. […] In patients with a long-standing immobile shoulder and chronic shoulder pain that is worse at night, tuberculosis should be suspected. […] Parkinson’s disease can also increase the risk of a frozen shoulder. In this condition, posture is severely impaired due to increased thoracic kyphosis and decreased mobility of the trunk. This can cause subacromial impingement syndrome and capsulitis. […] With thoracic and shoulder motion affected, it can lead to a frozen shoulder.

• #1 researchopenworld.com

  https://researchopenworld.com/recurrent-frozen-shoulder-an-autobiographical-case-report/

  Exact cause is not known. Evolution of synovial inflammation to capsular fibrosis and a Combination/progression of inflammation and fibrosis like Dupuytren’s chronic inflammatory response with immunomodulated fibroblastic proliferation. […] Contracture of the rotator interval, coracohumeral ligament, and anterior/inferior capsule is observed.

• #1 Frozen shoulder, adhesive capsulitis | Physica

  https://www.physica.com.au/frozen-shoulder-adhesive-capsulitis/

  Frozen shoulder is also termed adhesive capsulitis; whilst this term is still commonly used, it is scientifically inaccurate as there are no capsular adhesions (Yuan, Zhang, Li, 2017). Rather, frozen shoulder is associated with multi-regional synovitis and contracture of the capsule (Dias et al., 2005). […] There are some studies that question the presence of inflammation of the joint (synovitis) and rather describe a focal vascularity and synovial angiogenesis (increased capillary growth) (Dias et al., 2005; Yuan et al., 2017). […] The joint capsule (outer layer) is comprised of fibrous connective tissue that extends from the anatomical neck of the humerus to the outer rim of the glenoid. This capsule is formed by the superior, middle and inferior glenohumeral ligaments and it functions as the main stabiliser of the glenohumeral joint. The coracohumeral ligament, extending from the coracoid process to the greater tubercle of the humerus, supports the superior aspect of the joint; thickening of this ligament plays a role in the restricted range of movement in cases of frozen shoulder.

• #1 The pathophysiology associated with primary (idiopathic) frozen shoulder: A systematic review | BMC Musculoskeletal Disorders | Full Text

  https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-016-1190-9

  Frozen shoulder is a common yet poorly understood musculoskeletal condition, which for many, is associated with substantial and protracted morbidity. Understanding the pathology associated with this condition may help to improve management. […] Pathological changes in the anterior shoulder joint capsule and related structures were commonly reported. Imaging identified pathological changes occurring in the coracohumeral ligament, axillary fold and rotator interval. Obliteration of the subcoracoid fat triangle also appeared to be pathognomonic. Histological studies were inconclusive but suggested that immune, inflammatory and fibrotic changes where associated with primary frozen shoulder. […] The review identified substantial variations in interpretation of the Codman classification. Future research must clearly detail defined and standardised diagnostic guidelines, to allow for more accurate and definitive comparisons between findings in studies.

• #1 Adhesive capsulitis of the shoulder – Wikipedia

  https://en.wikipedia.org/wiki/Adhesive_capsulitis_of_the_shoulder

  Adhesive capsulitis, also known as frozen shoulder, is a condition associated with shoulder pain and stiffness. […] The underlying mechanism involves inflammation and scarring. […] The hardening of the shoulder joint capsule is central to the disease process. This is the result of scar tissue (adhesions) around the joint capsule. […] In the painful stage (stage I), there is evidence of inflammatory cytokines in the joint fluid. […] The main limiting factor in external rotation is due to the thickening of the coracohumeral ligament, which forms the roof of the rotator cuff and is a primary symptom of adhesive capsulitis. […] As the phases of adhesive capsulitis progress, the glenohumeral (GH) capsule begins to thicken and as a result the contraction of the capsule itself becomes the main reason as to why range of motion will be restricted in all planes of motion.

• #1 Idiopathic frozen shoulder

  https://www1.racgp.org.au/ajgp/2019/november/idiopathic-frozen-shoulder

  The pathognomonic sign of frozen shoulder is almost complete loss of active and passive external rotation. As mentioned previously, it is essential to be able to differentiate between limited range of movement secondary to a mechanical block due to glenohumeral capsular tightness and restriction, and limitation secondary to pain. […] Each phase of frozen shoulder is managed differently and is dependent on the predominant signs and symptoms. There are four key management principles that overlap into all phases, albeit the emphasis of each will vary depending on the phase. […] Intra-articular corticosteroid injections are safe and effective and have been shown to hasten improvement in pain and function. Many studies show benefit either alone or in conjunction with physiotherapy and/or a home-based exercise program.

• #1 Frozen Shoulder: Symptoms, Causes, Diagnosis, and Treatment | IntechOpen

  https://www.intechopen.com/chapters/80359

  This condition could be the expression of an immune response. […] Other studies have shown that frozen shoulder is associated with a dense collagen matrix containing fibroblasts and myofibroblasts, suggestive of a fibrotic process. […] Several studies have suggested the immune response overlaps with inflammatory synovitis, leading to capsular fibrosis in the later stages. […] There are many etiopathological hypotheses, and all studies suggest that both inflammation and fibrosis of the joint capsule are regulated by cytokines, growth factors, MMPs, and immune cells.

• #1 The puzzling pathophysiology of frozen shoulders – a scoping review | Journal of Experimental Orthopaedics | Full Text

  https://jeo-esska.springeropen.com/articles/10.1186/s40634-020-00307-w/tables/1

  Frozen shoulder starts with a hypervascular synovitis followed by diffuse fibroplasia with thickening and contracture of the capsule […] Active fibroblastic proliferation with differentiation into myofibroblasts and the deposition of thick nodular bands of collagen […] Hypervascular synovial hyperplasia with fibroblasts, occasional T-cells, B-cells and newly synthesized collagen type I and III was found. TGF-, PDGF, IL-1 and TNF- are involved in an inflammatory and fibrotic process in frozen shoulders […] The presence of mRNA for a large number of cytokines and growth was demonstrated in frozen shoulder capsular tissue […] Fibroblastic proliferation and an infiltrate of chronic inflammatory cells (mast cells, T cells, B cells and macrophages) was found […] NF-B, IL-6, MMP3, 1-integrin and VEGF were expressed in the synovial tissue of frozen shoulders

• #1

  https://link.springer.com/article/10.1007/s00776-013-0495-x

  The initiator of synovitis, however, remains still unclear. Based on the appearance of immune system cells, it is postulated that immunomodulated chronic inflammation may play some role in the pathogenesis of FS. […] It is still uncertain whether FS is a process similar to Dupuytrens contracture. There may be a failure of collagen remodeling in FS, which in part may result from a genetic failure to activate gelatinase A, or from elevation of the levels of the natural inhibitor of MMPs in the joint capsule. […] Future studies should be directed to give light on the initiator of inflammation, as well as of fibrosis, with the final aim to better treat or prevent FS.

• #1 Frozen Shoulder | Shoulder Pain Treatment Kingston

  https://www.osteopathypartnership.com/frozen-shoulder-and-adhesive-capsulitis-treatment/

  The Gleno-humeral joint (shoulder joint) is a synovial joint. Most joints in the body are. They have a very thin layer of cells (membrane) around the cartilage that produces synovial fluid that lubricates the two joint surfaces. It is believed that this synovial membrane and the layer beneath it (sub-synovial tissue) becomes inflamed. The body reacts to this by contracting the tissues that surround the joint causing fibrosis, pain and significantly reduced movement. […] One proposed reason is that the tendon of the Long head of the biceps that attaches just above the GH joint and within the fibrous capsule becomes damaged. This could be through a fall, a strain or any number of reasons. It becomes inflamed and because the tendon sits within the joint capsule the inflammation spreads to the synovium.

• #1 Frozen Shoulder – Adhesive Capsulitis – OrthoInfo – AAOS

  https://orthoinfo.aaos.org/en/diseases–conditions/frozen-shoulder/

  Frozen shoulder can develop after a shoulder has been immobilized (held in one position without moving) for a period of time due to surgery, a fracture, or other injury. Having patients move their shoulders soon after injury or surgery is one measure prescribed to prevent frozen shoulder. […] Surgery for frozen shoulder is typically offered during „Stage 2: Frozen.” The goal of surgery is to stretch and release the stiffened joint capsule. The most common methods include manipulation under anesthesia and shoulder arthroscopy.

• #1 The link between osteoporosis and frozen shoulder: exploring the therapeutic effect of TAK715 on reversing fibrosis and protecting against osteoporosis via the p38 MAPK signaling pathway | BMC Musculoskeletal Disorders | Full Text

  https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-024-08068-8

  Our bioinformatic analysis confirmed the vital role of the MAPK signaling pathway in the pathogenesis of both FS and OP, as well as its significant involvement in the crosstalk genes. […] The MAPK signal pathway, which mainly consists of ERK, Jun, and p38 MAPK, has been shown to be significantly important in fibrotic diseases such as renal fibrosis and pulmonary fibrosis. […] The overactivation of p38 MAPK is positively linked to the imbalance of cell apoptosis, which could trigger pathologic diseases such as liver fibrosis. […] The apoptosis process was similarly active as observed in liver fibrosis. […] Our results first confirmed that the FS side exhibited more osteoporosis than the control side, aligning with clinical findings. […] The p38 MAPK pathway is crucial for osteoclast maturation, and our results verified that TAK715 effectively inhibits osteoclast maturation in vitro. In animal experiments, rats treated with TAK715 showed less osteoporosis. We believe TAK715 is potent in protecting against osteoporosis by preventing osteoclast maturation.

• #1 Is 'frozen shoulder’ a genetic condition? Study finds links to specific genes | Wolters Kluwer

  https://www.wolterskluwer.com/en/news/is-frozen-shoulder-a-genetic-condition-study-finds-links-to-specific-genes

  Frozen shoulder, or adhesive capsulitis, is a common cause of shoulder pain and immobility. […] The authors believe their findings may lend new insights into the causes, prevention, and treatment of adhesive capsulitis. […] Loss of motion results from fibrosis (scarring or thickening) of the capsule around the shoulder joint. […] Recent studies have suggested that risk is also higher in people with affected relatives suggesting a possible genetic predisposition. […] The study identified three significant loci for frozen shoulder. […] The strongest association was found for gene variants located at a site called WNT7B. […] The findings may lend new insights into the development of adhesive capsulitis. […] The two newly reported loci, POU1F1 and MAU2, are involved with cell division, which might lend clues into the cellular mechanism by which frozen shoulder develops. […] Dr. Langhans and colleagues conclude: „Refining the genetic risk metric and including it in a larger clinical model could allow patients at risk for future adhesive capsulitis to be identified, leading to efforts at prevention, early diagnosis, and ultimately improved outcomes.”

• #1 Overcoming Frozen Shoulder – Fortaleza Rehab & Fitness

  https://www.lafortalezarehab.com/overcoming-frozen-shoulder/

  Adhesive capsulitis, also known as Frozen Shoulder, is a condition which involves shoulder pain and shoulder range of motion limitations. Typically, frozen shoulder is of insidious/gradual onset with no known of mechanism of injury, however history of shoulder trauma and surgery can increase risk of adhesive capsulitis. […] Adhesive capsulitis occurs due to constant inflammation of structures/musculature of the shoulder joint, which results in fibrosis/scarring. […] Frozen shoulder undergoes three stages: freezing, frozen, and thawing. The freezing stage is the first stage which includes insidious onset of pain. Freezing, the second stage involves restrictions in range motion (capsular pattern), with decreased pain. Thawing involves the gradual restoration of shoulder range of motion and strength.

• #1 Frozen Shoulder Treatments: J. Michael Bennett, MD, PA: Orthopaedic Surgeon

  https://www.orthopedicsportsdoctor.com/blog/frozen-shoulder-treatments

  So, what that means is that the capsule that surrounds the shoulder, so if this is the ball and the socket looking at front ways, this is looking at the shoulder from the top down. The capsule is this lining here in the front and the back of the shoulder. So, what happens is the capsule starts to tighten up, it starts to get very, very, very thickened and very inflamed. It happens on the front and the back of the shoulder, it happens below the shoulder itself, down here through the shoulder joint up here and basically, it starts to impede your motion. […] The frozen shoulder usually follows a curve so, what happens is that you start out at the baseline here and you really have mild pain or discomfort. And all of a sudden, the pain gets severe, severe, severe, really bad to the point that you dont want to move it at all. And then, finally gets to the point where it plateaus. And, the pain actually starts to subside, or it starts to just basically maintain a baseline.

• #1 Frozen Shoulder Treatments: J. Michael Bennett, MD, PA: Orthopaedic Surgeon

  https://www.orthopedicsportsdoctor.com/blog/frozen-shoulder-treatments

  What happens at this point here is where its frozen. That means you cant move it. What we need to do, as the orthopedic surgeon treating this shoulder, is somewhere during this steep curve right around here, anywhere along this line, we need to intervene and make sure that motion is maintained. […] Because, once you get to this frozen shoulder phase, the scar tissue, or the adhesions and the thickness of the capsule, may get to the point where you may actually have to undergo surgery.

• #1 4 Stages of Frozen Shoulder | Pathogenesis, Clinical Features, Symptoms, and Treatments

  https://www.alleviatepainclinic.com/blog/the-4-stages-of-frozen-shoulder-pathogenesis-clinical-features-symptoms-and-treatments/

  The pathogenesis of frozen shoulder remains incompletely understood, making it a subject of ongoing research and debate. However, it is generally believed that the condition is multifactorial, with various factors contributing to its development. In the initial stage, known as the pre-freezing or freezing stage, several key pathological processes come into play: […] The transition from the pre-freezing stage to the frozen stage is marked by a continued progression of fibrosis and contracture within the joint capsule. In this stage, pathogenesis is characterized by: […] The thawing stage represents a phase of gradual improvement in shoulder mobility. While the exact mechanisms underlying this stage are not fully understood, it is believed that the gradual breakdown of adhesions and collagen deposition leads to increased flexibility. […] The recovery stage represents the final phase of frozen shoulder, characterized by the gradual resolution of symptoms and the return of near-normal shoulder function. Pathogenesis in this stage involves the continued breakdown of collagen adhesions and the restoration of joint homeostasis.

• #1 Frozen shoulder, adhesive capsulitis | Physica

  https://www.physica.com.au/frozen-shoulder-adhesive-capsulitis/

  Imaging studies such as ultrasound (US) and magnetic resonance imaging (MRI) can identify coracohumeral ligament and joint capsule thickening, which is suggestive of frozen shoulder (Li et al., 2011). However, these signs may not be seen until later into the development of this condition (Yuan et al., 2017). […] A common procedure, which technically involves no surgery, is called manipulation under anaesthetic (Dias et al., 2005; Kelley et al., 2009; Kelley et al., 2013); this involves the forced movement of the shoulder to stretch and tear the capsule while the patient is under anaesthetic, in hopes to kick-start improvements in therapy. Another procedure used is termed a capsular release performed via arthroscopy. This operation involves the cutting and release of tight portions of the capsule (Cho et al., 2019; Dias et al., 2005); there are understandably more risks involved with this type of procedure, which is why it is usually utilised in cases failing other conservative forms of management.

• #1 Idiopathic frozen shoulder

  https://www1.racgp.org.au/ajgp/2019/november/idiopathic-frozen-shoulder

  Glenohumeral joint injection performed in the early stages of frozen shoulder by the primary care physician, with the necessary skills and equipment, can provide significant improvement in passive range of movement. […] Another injection-therapy modality is hydrodilatation, which involves injecting the glenohumeral joint capsule with a mixture of sodium chloride (0.9%) and corticosteroid made up to a volume of 40 mL. This procedure results in stretching of the capsule in addition to providing the benefits of the injected steroid.

• #1 Effectiveness of Glenohumeral Joint Dilatation for Treatment of Frozen Shoulder: A Systematic Review and Meta-analysis of Randomized Controlled Trials | Scientific Reports

  https://www.nature.com/articles/s41598-017-10895-w

  Frozen shoulder, also known as adhesive capsulitis, has a prevalence of 25% in the general population and is considered to be one of the most serious painful conditions involving the musculoskeletal system. The histopathology involves inflamed glenohumeral and subacromial synovium, hypertrophy of the coracohumeral ligament and fibrosis of the joint capsule. Intra-articular fluid infusion has been reported to invoke capsular stiffness and a steeply rising pressure, indicating poor compliance of the joint capsule; this is recognized as the predominant feature of frozen shoulder. […] Several experimental studies have indicated that hydrodilatation of the glenohumeral joint with normal saline and corticosteroid decreased intra-articular pressure and increased the shoulder volume capacity. Due to the potential physiological benefits of distending contracted shoulder joints, capsular distension has long been used as a treatment for frozen shoulder.

• #1 10 Facts About Frozen Shoulder

  https://www.4dhp.com/blog/10-facts-about-frozen-shoulder

  9. In the freezing stage, your General Practitioner or Physiotherapist may recommend to have cortisone steroid injections into the shoulder joint. […] However, they do not improve range or speed up resolution of frozen shoulder. […] 10. In the thawing stage, Physiotherapy-guided rehabilitation will be beneficial to facilitate restoration of shoulder function.

• #1 Frozen Shoulder – What is it? – Ultrasound Guided Injections

  https://www.ultrasound-guided-injections.co.uk/frozen-shoulder/

  Frozen shoulder is characterised by significant pain and progressive stiffness of the shoulder joint. More specifically, the capsule around the joint becomes inflamed and tight. […] It is unclear what causes frozen shoulder, but it is clear that this is a very painful and debilitating condition. […] The mechanism underlying the development of frozen shoulder is still unknown, however, factors known to increase the risk of onset are as follows: […] A recent systematic review by (Wang et al., 2016) revealed steroid injections to be the most effective treatment for frozen shoulder in stage one, the ‘painful stage’. […] Research has recommended that, for best results, a course of physiotherapy should be started within two weeks after receiving a shoulder joint injection. […] The current evidence base has shown that injections completed under ultrasound image guidance are more accurate at delivering the medication to the shoulder joint, and more effective at reducing pain and increasing function than landmark guided injections. […] Research has also revealed ultrasound guided injections can significantly reduce pain associated with frozen shoulder, particularly in short term.

• #1

  https://journals.lww.com/jcpc/fulltext/2017/06040/incidence_and_clinical_profile_of_patients_with.5.aspx

  Among the different types of cardiac surgeries, CABG was associated with significantly greater risk of causing frozen shoulder as compared to other forms of cardiac surgeries. The underlying mechanism for this association is difficult to explain but may be related to the differences in age and the prevalence of other risk factors such as diabetes. […] Thus, it may be suggested that regular postoperative physiotherapy to the upper limbs should be insisted to the patients by the medical and paramedical personnel as it can prevent the development of frozen shoulder in the immediate postoperative period.

• #1 The puzzling pathophysiology of frozen shoulders – a scoping review | Journal of Experimental Orthopaedics | Full Text

  https://jeo-esska.springeropen.com/articles/10.1186/s40634-020-00307-w

  The pathophysiology of frozen shoulders is a complex and multifactorial process. […] A state of low grade inflammation, as is associated with diabetes, cardiovascular disease and thyroid disorders, predisposes for the development of frozen shoulder. An early immune response with elevated levels of alarmins and binding to the receptor of advance glycation end products is present at the start of the cascade. Inflammatory cytokines, of which transforming growth factor-1 has a prominent role, together with mechanical stress stimulates Fibroblast proliferation and differentiation into myofibroblasts. This leads to an imbalance of extracellular matrix turnover resulting in a stiff and thickened glenohumeral capsule with abundance of type III collagen. […] An early inflammatory response at the onset of FS.

• #1 Biological Aspect of Pathophysiology for Frozen Shoulder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5994312/

  The underlying pathophysiologic processes of FS accompany capsular inflammation with subsequent fibrosis and this is modulated by mediators including inflammatory cytokines, growth factors, enzymes, and matrix metalloproteinases (MMPs). […] Therefore, determining the biological pathophysiology of FS is a pivotal milestone in the development of novel treatment for patients with FS. […] Studies characterizing the pathophysiology of FS are inconclusive but suggest both inflammation and fibrosis of the joint capsule mediated by cytokines, growth factors, MMPs, and immune cells. […] Further basic studies that use standardized protocols are imperative to identify the role of cytokines, growth factors, MMPs, and immune cells. […] The results of these studies will provide clarity into the control mechanisms of the pathogenesis of FS and help identify new therapeutic targets for its treatment.

• #2 Frozen Shoulder – Adhesive Capsulitis – OrthoInfo – AAOS

  https://orthoinfo.aaos.org/en/diseases–conditions/frozen-shoulder/

  Frozen shoulder, also called adhesive capsulitis, causes pain and stiffness in the shoulder. Over time, the shoulder becomes very hard to move. […] In frozen shoulder, the shoulder capsule thickens and becomes stiff and tight. Thick bands of tissue called adhesions develop. In many cases, there is less synovial fluid in the joint. […] The causes of frozen shoulder are not fully understood. There is no clear connection to arm dominance (the dominant arm is the arm you prefer to use for most tasks) or occupation. A few factors may put you more at risk for developing frozen shoulder. […] Frozen shoulder occurs much more often in people with diabetes. The reason for this is not known. In addition, diabetic patients with frozen shoulder tend to have a greater degree of stiffness that continues for a longer time before „thawing.”

• #2 Biological Aspect of Pathophysiology for Frozen Shoulder

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5994312/

  It is fairly well understood that frozen shoulder involves several stages, which reflect the series of process from capsular inflammation and fibrosis to spontaneous resolution of this fibrosis. […] However, the underlying pathophysiologic process remains poorly determined. […] Determining the pathophysiological processes of frozen shoulder is a pivotal milestone in the development of novel treatment for patients with frozen shoulder. […] Although articles for the pathophysiology of frozen shoulder provide inconsistent and inconclusive results, they have suggested both inflammation and fibrosis mediated by cytokines, growth factors, matrix metalloproteinases, and immune cells. […] Proinflammatory cytokines and growth factors released from immune cells control the action of fibroblast and matrix remodeling is regulated by the matrix metalloproteinases and their inhibitors.

• #2 The pathophysiology associated with primary (idiopathic) frozen shoulder: A systematic review | BMC Musculoskeletal Disorders | Full Text

  https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-016-1190-9

  The main findings with respect to pathology identified in this review are presented in Tables 5 and 6 and are summarised below. […] This review identified that the anterior shoulder structures in primary frozen shoulder were the location of greatest pathological change and in the subsequent clinical features of the disease, namely a loss of external rotation of the shoulder. The limited number of studies conducting histological analyses did not permit definitive conclusions pertaining to histological changes associated with PFS, however, and in line with previously published research, immune, inflammatory and fibrosis appear to play a role in the pathological process. The extent to which each component contributes and the variance associated with this cannot as yet be determined. […] Such studies have led to the suggestion that FS may begin as an immunological response which escalates to an inflammatory synovitis, eventually leading to fibrosis of the capsule and that future research should focus on disease.

• #2 Overcoming Frozen Shoulder – Fortaleza Rehab & Fitness

  https://www.lafortalezarehab.com/overcoming-frozen-shoulder/

  Adhesive capsulitis, also known as Frozen Shoulder, is a condition which involves shoulder pain and shoulder range of motion limitations. Typically, frozen shoulder is of insidious/gradual onset with no known of mechanism of injury, however history of shoulder trauma and surgery can increase risk of adhesive capsulitis. […] Adhesive capsulitis occurs due to constant inflammation of structures/musculature of the shoulder joint, which results in fibrosis/scarring. […] Frozen shoulder undergoes three stages: freezing, frozen, and thawing. The freezing stage is the first stage which includes insidious onset of pain. Freezing, the second stage involves restrictions in range motion (capsular pattern), with decreased pain. Thawing involves the gradual restoration of shoulder range of motion and strength.

• #2 The puzzling pathophysiology of frozen shoulders – a scoping review | Journal of Experimental Orthopaedics | Full Text

  https://jeo-esska.springeropen.com/articles/10.1186/s40634-020-00307-w

  Cytokines can regulate proliferation, activation and differentiation of fibroblasts, hereby dysregulating collagen synthesis. […] The mechanism of tissue fibrosis involves an imbalance in extracellular matrix turnover. […] The fibrotic effects of increased TIMP activity came to light when twelve patients were treated with Marimastat, a TIMP analogue for the treatment of gastric carcinoma. […] The MMP/TIMP ratio has been shown to be almost ten times lower in FS patients versus healthy controls. […] Transforming growth factor- one (TGF-1), and mechanical stress are two important factors contributing to contractility of fibroblasts. […] TGF-1 has been shown to stimulate contractility of fibroblasts in-vitro collagen gels and can be seen as a potent activator of myofibroblasts. […] Chronic low-grade inflammation might predispose to the development of FS.

• #2 The puzzling pathophysiology of frozen shoulders – a scoping review | Journal of Experimental Orthopaedics | Full Text

  https://jeo-esska.springeropen.com/articles/10.1186/s40634-020-00307-w/tables/1

  Frozen shoulder starts with a hypervascular synovitis followed by diffuse fibroplasia with thickening and contracture of the capsule […] Active fibroblastic proliferation with differentiation into myofibroblasts and the deposition of thick nodular bands of collagen […] Hypervascular synovial hyperplasia with fibroblasts, occasional T-cells, B-cells and newly synthesized collagen type I and III was found. TGF-, PDGF, IL-1 and TNF- are involved in an inflammatory and fibrotic process in frozen shoulders […] The presence of mRNA for a large number of cytokines and growth was demonstrated in frozen shoulder capsular tissue […] Fibroblastic proliferation and an infiltrate of chronic inflammatory cells (mast cells, T cells, B cells and macrophages) was found […] NF-B, IL-6, MMP3, 1-integrin and VEGF were expressed in the synovial tissue of frozen shoulders

• #2 The puzzling pathophysiology of frozen shoulders – a scoping review | Journal of Experimental Orthopaedics | Full Text

  https://jeo-esska.springeropen.com/articles/10.1186/s40634-020-00307-w/tables/1

  IL-1, IL-1, TNF-, COX-1 and COX-2 were expressed at higher levels in joint capsule of frozen shoulder patients compared to controls. In the subacromial bursa, IL-1, TNF- and COX-2 were expressed at higher levels […] -catenin and IGF-2 expression were found to be elevated in frozen shoulders compared to controls […] Upregulation of acid sensing ion channels (ACICs) was found in capsular tissue and synovial fluid of frozen shoulder patients […] Elevated expression of Tenascin C and Fibronectin 1 mRNA was found in capsular tissue of frozen shoulder patients […] Intra articular corticosteroid injection reduces fibrosis, vascular hyperplasia and myofibroblast differentiation […] Immunoreactivity of AGEs was stronger in frozen shoulder capsules compared to controls […] 147 genes were upregulated and 24 downregulated in capsular tissue of frozen shoulder patients compared to controls

• #2 The puzzling pathophysiology of frozen shoulders – a scoping review | Journal of Experimental Orthopaedics | Full Text

  https://jeo-esska.springeropen.com/articles/10.1186/s40634-020-00307-w/tables/1

  Immunoreactivity of alarmins was stronger in frozen shoulder patients. The expression of the alarmin HMGB1 correlated with the severity of pain […] The pathophysiology might differ between the upper and lower parts of the joint capsule. In the RI and MGHL samples, different proteins were higher expressed compared to the IGHL samples […] Fibroblasts in FS have activated phenotype with an increased expression of fibroblast activation markers. Cultured FS fibroblasts produced elevated levels of inflammatory proteins (IL-6, IL-8, CCL-20) […] Overexpression of IL-6, MMP-2 and MMP-9 may be associated with frozen shoulder […] Inflammation and ECM remodelling were the most significant and highly enriched processes in frozen shoulder. MMP13 expression was increased and TNF- expression was reduced in frozen shoulders […] AGEs and HMGB1 might play important roles in the pathogenesis of frozen shoulder. Gene expression levels of RAGE, HMGB1, TLR2, TLR4 and NF-B were significantly greater in frozen shoulders compared to controls.

• #2 The puzzling pathophysiology of frozen shoulders – a scoping review | Journal of Experimental Orthopaedics | Full Text

  https://jeo-esska.springeropen.com/articles/10.1186/s40634-020-00307-w/tables/1

  A higher expression of mRNA for TGF- and several MMPs was found […] Inflammatory (IL-6 and IL-8) and fibrogenic (MMP3) cytokines were expressed at a higher level in frozen shoulders compared to controls […] Treatment of cultured glenohumeral/synovial fibroblast from frozen shoulder patients with hyaluronan inhibited cell proliferation and expression of adhesion related procollagens and cytokines […] A higher number of cells, stiffer capsular tissue and increased gene expression related to fibrosis (COL1A1, PDGF-B) inflammation (IL-1) and chondrogenesis was found […] Increased expression of nerve growth factor receptor and new nerve fibers were found in frozen shoulder capsular tissue compared to controls […] ICAM-1 was increased in capsular tissue, synovial fluid, and serum of frozen shoulder patients compared to controls

• #2

  https://www.orthobullets.com/shoulder-and-elbow/3059/adhesive-capsulitis-frozen-shoulder

  post-surgical (following rotator cuff repair or axillary dissection for malignancy) […] inflammatory process causing fibroblastic proliferation of joint capsule leading to thickening, fibrosis, and adherence of the capsule to itself and humerus […] fibroblasts/myofibroblasts with abundant Type III collagen present […] leads to mechanical block to motion […] essential lesion involves the coracohumeral ligament and rotator interval capsule.

• #2 Frozen Shoulder – Physio Guide to Pathophysiology & Evidence Based Treatment – Bradley Physio

  https://www.bradleyphysio.co.uk/frozen-shoulder-physio-guide-to-pathophysiology-evidence-based-treatment

  We now know that frozen shoulder, is a painful inflammatory disorder with progressive fibrosis of the shoulder capsule but its pathogenesis is still unknown (Bak and Isaaksson, 2019). […] Due to the variety and conflicting evidence over the years stemming from the varying definitions of frozen shoulder, Lewis (2015), compiled a summary of abnormalities which were regularly seen in patients with frozen shoulder from 1952 through to 2009 yet there was still some uncertainty regarding the inflammatory changes. These were; […] Thickening and fibrosis of the rotator interval […] Scaring of the subscapular recess (between biceps and subscapularis tendons) […] Neovascularity […] Increased cytokine concentrations […] Contraction and fibrosis of the coracohumeral ligament […] Proliferation of fibroblasts and myofibroblasts […] Presence of contractile proteins.

• #2 Adhesive Capsulitis of the Shoulder: Current Concepts on the Diagnostic Work-Up and Evidence-Based Protocol for Radiological Evaluation

  https://www.mdpi.com/2075-4418/13/22/3410

  The existence of an inflammatory process underpinning the fibrotic response is suggested by the recent demonstration of inflammatory cytokines, neoangiogenesis, and neoinnervation in capsular and bursal samplings. Of note, the overexpression of intercellular adhesion molecule-1 (ICAM-1), which is a transmembrane protein involved in the inflammatory response, has been observed in both patients with AC and diabetes, possibly explaining the common association between the two conditions.

• #2 researchopenworld.com

  https://researchopenworld.com/recurrent-frozen-shoulder-an-autobiographical-case-report/

  Frozen shoulder (FS) remains one of the most debated and ill-understood conditions causing painful shoulder. […] Adhesive Capsulitis of the Shoulder (ACOS) commonly known as Frozen shoulder (FS) is a condition of uncertain aetiology characterized by significant restriction of both active and passive shoulder movements that occur in the absence of a known intrinsic shoulder disorder. […] The modern evidence of frozen shoulder pathogenesis involves fibrosis and/or contracture of the tendons, joint capsule, and other soft tissues surrounding the glenohumeral joint specifically the rotator cuff interval. In severe cases, the RC interval is “obliterated,” and the coracohumeral ligament is “transformed into a tough contracted band,” like arthritis of soft tissues. […] A major role of inflammatory mediators (interleukins, cytokines, B- and T-lymphocytes, growth factors, matrix metalloproteinases, tumour necrosis factors and fibroblast activation markers) is postulated in FS characterized by intense inflammatory changes in capsule indicating a role of and disturbance in local collagen translation, which result in global fibroplasia. The capsule of the FS appears thick, congested, and inflamed, particularly around the rotator interval and anteroinferior capsule along with thickened coracohumeral ligament (CHL) and superior-middle-inferior glenohumeral ligaments to the naked eyes during surgery. This results in loss of flexion, abduction, and rotations. Microscopic tissue samples reveal dense collagen matrix and high population of fibroblasts and contractile myofibroblasts, a process like Dupuytren’s contracture, with the fibrotic process predominantly limited to anterior capsule.

• #2 Frozen Shoulder – Adhesive Capsulitis | Orthopedic Specialists of Seattle

  https://orthopedicspecialistsofseattle.com/frozen-shoulder/

  Adhesive capsulitis, more commonly referred to as frozen shoulder, is a process in which the range of motion in the shoulder joint becomes gradually reduced over time. […] Arthroscopic examination of patients with the condition has shown evidence of both inflammation and scarring taking place within the shoulder joint, however the underlying mechanism behind the development of these findings is still unclear. […] There are also several diseases associated with the development of frozen shoulder. Patients with diabetes, thyroid disease, autoimmune diseases or a recent stroke have an increased risk of developing frozen shoulder at this point in time the reasoning behind these associations is not entirely clear. […] A steroid injection helps to reduce local inflammation, and therefore pain and stiffness.

• #2 Frozen shoulder (adhesive capsulitis) – UpToDate

  https://www.uptodate.com/contents/frozen-shoulder-adhesive-capsulitis

  Frozen shoulder can be primary (or idiopathic) but is often associated with other diseases and conditions. […] Patients with diabetes mellitus are at greater risk of developing frozen shoulder. In a meta-analysis of six case-control studies, diabetics were found to be over three times more likely to develop adhesive capsulitis, while the overall prevalence among diabetics is reported to be 10 to 20 percent. […] Prevalence among long-term diabetics may be even higher. A cross-sectional study reported the point prevalence of frozen shoulder in patients with long-lasting type 1 diabetes to be as high as 59 percent, with a lifetime prevalence 76 percent.

• #2 Understanding Causes And Symptoms Of Frozen Shoulder

  https://centenoschultz.com/condition/frozen-shoulder/

  Natural degeneration: Degeneration of the tendons and the capsule can attract inflammatory cells. This can make the capsule stiff and lead to a frozen shoulder. […] In diabetes, studies show that higher levels of glycated hemoglobin (HbA1c), advanced glycation end products (AGEs), vascular endothelial growth factor (VEGF), interleukin-1 beta (IL-1) can cause changes in the rotator cuff tendons and increase capsular stiffness. This can cause adhesive capsulitis. […] Hyperthyroidism is an autoimmune condition in which the thyroid is highly active. Graves disease is an overactive thyroid disorder that results in high amounts of interleukin-2 (IL-2), interferon- (IFN-), and tumor necrosis factor- (TNF-) cytokines being secreted by Th1 cells, causing the production of fibroblast cells. […] These fibroblast cells lay down scar tissue which causes the joint capsule to stiffen, ultimately leading to a frozen shoulder.

• #2 The pathophysiology associated with primary (idiopathic) frozen shoulder: A systematic review | BMC Musculoskeletal Disorders | Full Text

  https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-016-1190-9

  Frozen shoulder is a common yet poorly understood musculoskeletal condition, which for many, is associated with substantial and protracted morbidity. Understanding the pathology associated with this condition may help to improve management. […] Pathological changes in the anterior shoulder joint capsule and related structures were commonly reported. Imaging identified pathological changes occurring in the coracohumeral ligament, axillary fold and rotator interval. Obliteration of the subcoracoid fat triangle also appeared to be pathognomonic. Histological studies were inconclusive but suggested that immune, inflammatory and fibrotic changes where associated with primary frozen shoulder. […] The review identified substantial variations in interpretation of the Codman classification. Future research must clearly detail defined and standardised diagnostic guidelines, to allow for more accurate and definitive comparisons between findings in studies.

• #2 researchopenworld.com

  https://researchopenworld.com/recurrent-frozen-shoulder-an-autobiographical-case-report/

  Exact cause is not known. Evolution of synovial inflammation to capsular fibrosis and a Combination/progression of inflammation and fibrosis like Dupuytren’s chronic inflammatory response with immunomodulated fibroblastic proliferation. […] Contracture of the rotator interval, coracohumeral ligament, and anterior/inferior capsule is observed.

• #2 Effectiveness of Glenohumeral Joint Dilatation for Treatment of Frozen Shoulder: A Systematic Review and Meta-analysis of Randomized Controlled Trials | Scientific Reports

  https://www.nature.com/articles/s41598-017-10895-w

  Frozen shoulder, also known as adhesive capsulitis, has a prevalence of 25% in the general population and is considered to be one of the most serious painful conditions involving the musculoskeletal system. The histopathology involves inflamed glenohumeral and subacromial synovium, hypertrophy of the coracohumeral ligament and fibrosis of the joint capsule. Intra-articular fluid infusion has been reported to invoke capsular stiffness and a steeply rising pressure, indicating poor compliance of the joint capsule; this is recognized as the predominant feature of frozen shoulder. […] Several experimental studies have indicated that hydrodilatation of the glenohumeral joint with normal saline and corticosteroid decreased intra-articular pressure and increased the shoulder volume capacity. Due to the potential physiological benefits of distending contracted shoulder joints, capsular distension has long been used as a treatment for frozen shoulder.

• #2

  https://journals.lww.com/jcpc/fulltext/2017/06040/incidence_and_clinical_profile_of_patients_with.5.aspx

  Frozen shoulder is a condition characterized by pain and global restriction of movement with loss of external rotation. Cardiac surgery may predispose frozen shoulder as patients tend to immobilize their upper limbs after surgery. […] The present study shows that cardiac surgery increases the risk of developing frozen shoulder during the early postoperative period. Statistically significant correlation existed between positive LAM test and age of the patients, presence of diabetes mellitus and hypertension, type of cardiac surgery, and the regularity of physiotherapy follow-up. […] Frozen shoulder begins with an early phase of pain which eventually leads to stiffness. This suggests that there is an inflammatory response which later evolves into a fibrotic reaction. Currently accepted theory is that there is an initial active fibroblastic proliferation with subsequent transformation of fibroblasts to myofibroblasts. This causes an inflammatory contracture of the shoulder, decrease in the capsular volume, and restriction of the glenohumeral movements.

• #2 Frozen Shoulder Treatments: J. Michael Bennett, MD, PA: Orthopaedic Surgeon

  https://www.orthopedicsportsdoctor.com/blog/frozen-shoulder-treatments

  So, what that means is that the capsule that surrounds the shoulder, so if this is the ball and the socket looking at front ways, this is looking at the shoulder from the top down. The capsule is this lining here in the front and the back of the shoulder. So, what happens is the capsule starts to tighten up, it starts to get very, very, very thickened and very inflamed. It happens on the front and the back of the shoulder, it happens below the shoulder itself, down here through the shoulder joint up here and basically, it starts to impede your motion. […] The frozen shoulder usually follows a curve so, what happens is that you start out at the baseline here and you really have mild pain or discomfort. And all of a sudden, the pain gets severe, severe, severe, really bad to the point that you dont want to move it at all. And then, finally gets to the point where it plateaus. And, the pain actually starts to subside, or it starts to just basically maintain a baseline.

• #2 4 Stages of Frozen Shoulder | Pathogenesis, Clinical Features, Symptoms, and Treatments

  https://www.alleviatepainclinic.com/blog/the-4-stages-of-frozen-shoulder-pathogenesis-clinical-features-symptoms-and-treatments/

  The pathogenesis of frozen shoulder remains incompletely understood, making it a subject of ongoing research and debate. However, it is generally believed that the condition is multifactorial, with various factors contributing to its development. In the initial stage, known as the pre-freezing or freezing stage, several key pathological processes come into play: […] The transition from the pre-freezing stage to the frozen stage is marked by a continued progression of fibrosis and contracture within the joint capsule. In this stage, pathogenesis is characterized by: […] The thawing stage represents a phase of gradual improvement in shoulder mobility. While the exact mechanisms underlying this stage are not fully understood, it is believed that the gradual breakdown of adhesions and collagen deposition leads to increased flexibility. […] The recovery stage represents the final phase of frozen shoulder, characterized by the gradual resolution of symptoms and the return of near-normal shoulder function. Pathogenesis in this stage involves the continued breakdown of collagen adhesions and the restoration of joint homeostasis.

• #2 Frozen Shoulder – What is it? – Ultrasound Guided Injections

  https://www.ultrasound-guided-injections.co.uk/frozen-shoulder/

  Frozen shoulder is characterised by significant pain and progressive stiffness of the shoulder joint. More specifically, the capsule around the joint becomes inflamed and tight. […] It is unclear what causes frozen shoulder, but it is clear that this is a very painful and debilitating condition. […] The mechanism underlying the development of frozen shoulder is still unknown, however, factors known to increase the risk of onset are as follows: […] A recent systematic review by (Wang et al., 2016) revealed steroid injections to be the most effective treatment for frozen shoulder in stage one, the ‘painful stage’. […] Research has recommended that, for best results, a course of physiotherapy should be started within two weeks after receiving a shoulder joint injection. […] The current evidence base has shown that injections completed under ultrasound image guidance are more accurate at delivering the medication to the shoulder joint, and more effective at reducing pain and increasing function than landmark guided injections. […] Research has also revealed ultrasound guided injections can significantly reduce pain associated with frozen shoulder, particularly in short term.

• #2 The puzzling pathophysiology of frozen shoulders – a scoping review | Journal of Experimental Orthopaedics | Full Text

  https://jeo-esska.springeropen.com/articles/10.1186/s40634-020-00307-w

  Several authors have hypothesized an association with a chronic state of low grade inflammation which might predispose to the development of FS. […] An increasing amount of evidence supports a chronic state of low-grade inflammation as an important predisposing factor for the development of FS. […] The complexity of the pathophysiology of FS is outlined in this review. A state of low grade inflammation, as is associated with DM, cardiovascular disease and thyroid disorders, predisposes for the development of FS. An early immune response with elevated levels of alarmins such as HMGB1 and binding to the receptor of AGE starts the cascade of inflammation. Activation of the NF-B pathway together with mechanical stress stimulates release of inflammatory cytokines, of which TGF- has a prominent role. Fibroblasts proliferate, become activated and differentiate into myofibroblasts. This results in an imbalance of ECM turnover and a stiff and thickened glenohumeral capsule with abundance of type III collagen.

• #3 The puzzling pathophysiology of frozen shoulders – a scoping review | Journal of Experimental Orthopaedics | Full Text

  https://jeo-esska.springeropen.com/articles/10.1186/s40634-020-00307-w

  The pathophysiology of frozen shoulders is a complex and multifactorial process. […] A state of low grade inflammation, as is associated with diabetes, cardiovascular disease and thyroid disorders, predisposes for the development of frozen shoulder. An early immune response with elevated levels of alarmins and binding to the receptor of advance glycation end products is present at the start of the cascade. Inflammatory cytokines, of which transforming growth factor-1 has a prominent role, together with mechanical stress stimulates Fibroblast proliferation and differentiation into myofibroblasts. This leads to an imbalance of extracellular matrix turnover resulting in a stiff and thickened glenohumeral capsule with abundance of type III collagen. […] An early inflammatory response at the onset of FS.

• #3

  https://link.springer.com/article/10.1007/s00776-013-0495-x

  Primary frozen shoulder (FS) is a painful contracture of the glenohumeral joint that arises spontaneously without an obvious preceding event. […] Many studies indicate that the main pathology is an inflammatory contracture of the shoulder joint capsule. This is associated with an increased amount of collagen, fibrotic growth factors such as transforming growth factor-beta, and inflammatory cytokines such as tumor necrosis factor-alpha and interleukins. […] Primary FS shows fibrosis of the joint capsule, associated with preceding synovitis. The initiator of synovitis, however, still remains unclear. Future studies should be directed to give light to the pathogenesis of inflammation to better treat or prevent primary FS. […] Most of the studies indicate that FS involves both synovial inflammation and capsular fibrosis. Since characteristically pain precedes stiffness in FS, it is most likely that inflammation evolves to fibrosis. Cytokines such as TNF-alpha and ILs will produce synovitis in both the glenohumeral joint and the subacromial bursa, whereas matrix-bound TGF-beta may act as a persistent stimulus, resulting in capsular fibrosis.

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