Efficacy of hypertonic dextrose proliferation therapy in the treatment of rotator cuff lesions: a meta-analysis.

BACKGROUND: One of the most prevalent illnesses of the shoulder is rotator cuff tendinosis, which is also a major contributor to shoulder discomfort and shoulder joint dysfunction. According to statistics, rotator cuff tendinosis occurs in 0.3-5.5% of cases and affects 0.5-7.4% of people annually. It will be necessary to conduct a meta-analysis to evaluate the efficacy of hypertonic glucose proliferation therapy in the treatment of rotator cuff problems. METHODS: The databases Cochrane PubMed, Library, Web of Science and EMbase, are retrieved by the computer. Individuals with rotator cuff lesions in the intervention group were treated with hypertonic dextrose proliferation therapy, whereas individuals in the control condition were treated with a placebo. Outcome markers for rotator cuff lesions patients; Pursuant to studies, the visual analogue scale (VAS) score, the shoulder pain & disability index (SPADI), & other metrics are used to evaluate the effects of hypertonic dextrose proliferation treatment on individuals with rotator cuff diseases. After carefully evaluating the calibre of the literature, data analysis was performed utilising the RevMan 5.3 programme. RESULTS: Meta-analysis finally contained 6 papers. In six investigations, the test & control group's VAS scores improved, with the test team's score considerably outperforming the control team [standardized mean difference (SMD): 1.10; 95% Cl: 0.37,1.83; P < 0.01], shoulder pain and disability index (SPADI) score (SMD:8.13; 95% Cl: 5.34,10.91; P < 0.01), Flexion (SMD:5.73; 95% Cl: 0.99,10.47; P < 0.05), Abduction (SMD:6.49; 95% Cl: 0.66,12.31; P < 0.05), Internal rotation (SMD:-1.74; 95% Cl: -4.25,0.78; P = 0.176) and External rotation (SMD:2.78; 95% Cl: -0.13,5.69; P = 0.062). CONCLUSION: The findings of this study suggest that individuals with rotator cuff injuries may benefit from hypertonic dextrose proliferation treatment based on the visual analogue scale (VAS) score, the Shoulder Pain and Disability Index (SPADI) score, Flexion, & Abduction. These results must, nevertheless, be supported by high-caliber follow-up research.

A pilot study exploring the use of hyaluronic acid in treating insertional achilles tendinopathy.

PURPOSE: This study explores the use of ultrasound-guided Hyaluronic Acid (HA) injections for Insertional Achilles Tendinopathy (IAT). METHODS: A cohort of 15 ankles diagnosed with IAT received three weekly ultrasound-guided HA injections. The Victorian Institute of Sport Assessment - Achilles (VISA-A) questionnaire scored the severity of symptoms and functional impairment before treatment, and at one and six months post-treatment. RESULTS: Significant improvement was observed in VISA-A scores post-treatment, rising from an average baseline of 34.8 ± 15.2 (11-63) to 53.6 ± 20.9 (15-77) after one month, and then to 50.7 ± 18.6 (20-75) after six months. No adverse reactions were noted, underscoring the safety of the intervention. CONCLUSION: The pilot study presents HA injections as a potentially effective treatment for IAT, while interpretation of these findings must take into account the variability in results, indicating a range of patient responses. It encourages further research to confirm these findings and to explore HA's full potential in managing IAT, despite the limitations of a small sample size and lack of control group.

Evaluation of Anti-Nociceptive, Anti-Inflammatory, and Anti-Fibrotic effects of noscapine against a rat model of Achilles tendinopathy.

During tendinopathy, prolonged inflammation results in fibrosis and the adherence of tendons to the adjacent tissues, causing discomfort and movement disorders. As a natural compound, noscapine has several anti-inflammatory and anti-fibrotic properties. Therefore, we aimed to investigate the effects of noscapine against a rat model of tendinopathy. We created a surgical rat model of Achilles tendon damage to emulate tendinopathy. Briefly, an incision was made on the Achilles tendon, and it was then sutured using an absorbable surgical thread. Immediately, the injured area was topically treated with the vehicle, noscapine (0.2, 0.6, and 1.8 mg/kg), or dexamethasone (0.1 mg/kg) as a positive control. During the 19-day follow-up period, animals were assessed for weight, behavior, pain, and motor coordination testing. On day 20th, the rats were sacrificed, and the tendon tissue was isolated for macroscopic scoring, microscopic (H&E, Masson's trichrome, Ki67, p53) analyses, and cytokine secretion levels. The levels of macroscopic parameters, including thermal hyperalgesia, mechanical and cold allodynia, deterioration of motor coordination, tendon adhesion score, and microscopic indices, namely histological adhesion, vascular prominence and angiogenesis, and Ki67 and p53 levels, as well as fibrotic and inflammatory biomarkers (IL-6, TNF-α, TGF-ß, VEGF) were significantly increased in the vehicle group compared to the sham group (P < 0.05-0.001 for all cases). In contrast, the administration of noscapine (0.2, 0.6, and 1.8 mg/kg) attenuated the pain, fibrosis, and inflammatory indices in a dose-dependent manner compared to the vehicle group (P < 0.05-0.001). Histological research indicated that noscapine 0.6 and 1.8 mg/kg had the most remarkable healing effects. Interestingly, two higher doses of noscapine had impacts similar to those of the positive control group in both clinical and paraclinical assessments. Taken together, our findings suggested that noscapine could be a promising medicine for treating tendinopathies.

Anti-inflammatory effects of sericin and swimming exercise in treating experimental Achilles tendinopathy in rat.

The aim of this study was to assess the effectiveness of combining sericin with swimming exercise as a treatment for type-I collagenase-induced Achilles tendinopathy (AT) in rats, with a focus on inflammatory cytokines. An experimental AT model was established using type-I collagenase in male Sprague-Dawley rats, categorized into five groups: Group 1 (Control + Saline), Group 2 (AT), Group 3 (AT + exercise), Group 4 (AT + sericin), and Group 5 (AT + sericin + exercise). Intratendinous sericin administration (0.8 g/kg/mL) took place from days 3 to 6, coupled with 30 min daily swimming exercise sessions (5 days/week, 4 weeks). Serum samples were analyzed using ELISA for tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-10 (IL-10), and total antioxidant-oxidant status (TAS-TOS), alongside histopathological and immunohistochemical assessments of Achilles tendon samples. Elevated TNF-α and IL-1ß and decreased IL-10 levels were evident in Group 2; Of these, TNF-α and IL-1ß were effectively reduced and IL-10 increased across all treatment groups, particularly groups 4 and 5. Serum TAS was notably lower in Group 2 and significantly increased in Group 5 compared to Group 2. Histopathologically, Group 2 displayed severe degeneration, irregular fibers, and round cell nuclei, while Group 5 exhibited decreased degeneration and spindle-shaped fibers. The Bonar score increased in Group 2 and decreased in groups 4 and 5. Collagen type-I alpha-1 (Col1A1) expression was notably lower in Group 2 (P = 0.001) and significantly increased in groups 4 and 5 compared to Group 2 (P = 0.011 and 0.028, respectively). This study underscores the potential of sericin and swimming exercises in mitigating inflammation and oxidative stress linked to AT pathogenesis, presenting a promising combined therapeutic strategy.

A prospective study of 100 patients with rotator cuff tendinopathy showed no correlation between subacromial bursitis and the efficacy of ultrasound-guided corticosteroid injection.

OBJECTIVES: The objective of this study was to determine whether the presence of subacromial bursitis in patients with rotator cuff tendinopathy (RCT) was associated with a better outcome after ultrasound (US)-guided subacromial corticosteroid injection. METHODS: A single-center prospective study was performed including patients referred for subacromial injection to manage RCT. At baseline, all patients received an US-guided intra-bursal injection of betamethasone (1 ml). The primary endpoint was reduced pain 3 months (M3) after the procedure: a good responder was defined by a decrease in Visual Analogue Scale pain of more than 30%. Secondary endpoints included functional recovery assessed by the Oxford Shoulder Score (OSS) and clinical success at 6 weeks (W6). We also explored the association between good clinical response and other factors, such as US or X-ray features. RESULTS: One hundred patients were included and 49 presented with subacromial bursitis. At M3, 60% of patients (54/100) were considered good responders. The rate of good responders did not differ between the bursitis and non-bursitis groups (p = 0.6). During follow-up, OSS improved over time whether bursitis was present or not. We did not find any US or X-ray features significantly associated with a favorable clinical outcome. CONCLUSION: The presence of subacromial bursitis did not influence clinical outcomes at 3 months post-subacromial injection in patients suffering from RCT. CLINICAL RELEVANCE STATEMENT: The presence of subacromial bursitis did not influence clinical outcomes at 3 months post-subacromial corticosteroid injection in patients with rotator cuff tendinopathy. For patient management, looking for ultrasonographic signs of bursitis does not appear relevant for the indication of the injection. KEY POINTS: • Ultrasound-guided subacromial corticosteroid injections led to a significant improvement in 60% of patients suffering from rotator cuff tendinopathy. • The presence of subacromial bursitis was not associated with better improvement at 3 months post-injection. • Except for the Minnesota score referring to job satisfaction, we did not find any baseline clinical, X-ray, or ultrasound characteristics associated with a successful outcome.

Combined extract (Curcuma longa-Glycyrrhiza glabra) alleviates the inflammations of Achilles tendinopathy in Wistar rats.

OBJECTIVE: Achilles tendinopathy is a frequent pathological condition in adults with overused ankles, causing microtrauma, inducing tenocyte apoptosis and inflammatory response. Common treatment involves oral prescription or injection of anti-inflammatory agents, surgery, or shock-wave therapy. However, prolonged administration is not advisable due to adverse effects. Therefore, a novel and safe regimen is needed. Curcuma longa and Glycyrrhiza glabra extracts are known for their anti-inflammatory effects owing to their active compounds (curcumin and glycyrrhizin, respectively). This study aimed to determine the effect of combined extracts of Curcuma longa and Glycyrrhiza glabra on tendon healing in an animal model of Achilles tendinopathy (Wistar rats). MATERIALS AND METHODS: This study took place from February to May 2022 and compared the regimens administered to 32 animal models of Wistar rats with 4 healthy rats as a control group to determine the most effective therapeutic regimen: immobilization, immobilization with ibuprofen, or immobilization with the combined extract. The outcomes were measured to find which intervention provided the lowest inflammatory markers [High Mobility Group Box-1 (HMGB-1), Tumor Necrosis Factor-α (TNF-α), Chemokin motif ligand 12 (CXCL-12)], and improved tissue morphology represented by the BONAR score, decreased cross-sectional area (CSA), and increased Macrophage 2 (M2) differentiation. RESULTS: After Achilles tendinopathy was induced, total immobilization (I1) was proven to be the most effective with the lowest CSA, whereas immobilization+175 mg/kg Curcuma longa+110 mg/kg Glycyrrhiza glabra extract (I5) was the most effective with the lowest HMGB-1 levels and the lowest CXCL-12 levels. Immobilization+131 mg/kg Curcuma longa+82.5 mg/kg Glycyrrhiza glabra extract (I6) was the most effective with the lowest Bonar score, while immobilization+87.5 mg/kg Curcuma longa+55 mg/kg Glycyrrhiza glabra extract (I7) was proven to be the most effective with the highest M2 coverage area and the lowest TNF-α levels. CONCLUSIONS: We found that combined extract therapy was the most effective intervention for treating Achilles tendinopathy due to its ability to provide the lowest inflammatory markers.

Is Ultrasound (US)-Guided Platelet-Rich Plasma Injection More Efficacious as a Treatment Modality for Lateral Elbow Tendinopathy Than US-Guided Steroid Injection?: A Prospective Triple-Blinded Study with Midterm Follow-up.

Background: Lateral elbow tendinopathy (LET) has an array of modalities described for its management. The present study analyzed two modalities used for managing the condition. Methods: The present study included 64 non-athletes with LET who failed conservative treatment that included avoiding strenuous activities, ice-fomentation, non-steroidal anti-inflammatory drugs, bracing, and physiotherapy for 6 months. A random allocation of the participants was done, with one group injected with platelet-rich plasma (PRP) and the other group with corticosteroids. The procedure was performed by the same blinded orthopedic surgeon after localizing the pathology using ultrasound. Visual analog scale (VAS) scores, disabilities of the arm, shoulder and hand (DASH) scores, Patient-Rated Tennis Elbow Evaluation (PRTEE) scores, and handgrip strengths were recorded by blinded observers other than the surgeon administering the injection. Results: The average age of the patients was 40 years. The mean VAS score at the latest follow-up of 2 years in the PRP group was 1.25 and it was significantly better than the score of 3.68 in the steroid group (p < 0.001). The mean DASH score at the latest follow-up of 2 years in the PRP group was 4.00 and it was significantly better than the score of 7.43 in the steroid group (p < 0.001). The mean PRTEE score at the latest follow-up of 2 years in the PRP group was 3.96 and it was significantly better than the score of 7.53 in the steroid group (p < 0.001). The scores were better in the steroid group at a short-term follow-up of 3 months (p < 0.05), while they were better in the PRP group at a long-term follow-up of 2 years (p < 0.05). Hand-grip strength was comparable in the PRP group (84.43 kg force) and steroid group (76.71 kg force) at the end of the 2-year follow-up with no statistically significant difference (p = 0.149). Conclusions: Corticosteroid injections alleviated symptoms of LET over short-term follow-up providing quicker symptomatic relief; however, the effect faded off over the long term. PRP injections provided a more gradual but sustained improvement over the long-term follow-up, indicating the biological healing potential of PRP.

The healing effects of thymoquinone on experimentally induced traumatic tendinopathy in rabbits.

OBJECTIVES: Thymoquinone is a major bioactive compound present in the black seeds of the Nigella sativa. Tendon injuries are almost 50% of all musculoskeletal injuries. The recovery of tendon after surgery has become a significant challenge in orthopedics. DESIGN: The purpose of this study was to investigate the healing effect of thymoquinone injections in 40 New Zealand rabbits tendon traumatic models. MATERIALS AND METHODS: Tendinopathy was induced by trauma using surgical forceps on the Achilles tendon. Animals were randomly divided into 4 groups: (1) normal saline injection (control), (2) DMSO injection, (3) thymoquinone 5% w/w injection, and (4) thymoquinone 10% w/w injection. Forty-two days after surgery, biochemical and histopathological evaluations were done, and biomechanical evaluation was conducted 70 days after surgery. RESULTS: Breakpoint and yield points in treatment groups were significantly higher compared to control and DMSO groups. Hydroxyproline content in the 10% thymoquinone receiving group was higher than all groups. Edema and hemorrhage in the histopathological evaluation were significantly lower in the thymoquinone 10% and thymoquinone 5% receiving groups compared to control and DMSO groups. Collagen fibers, collagen fibers with fibrocytes, and collagen fibers with fibroblasts were significantly higher in the thymoquinone 10% and thymoquinone 5% receiving groups compared to control groups. CONCLUSIONS: Thymoquinone injection in the tendon in the concentration of 10% w/w is a simple and low-cost healing agent that could enhance mechanical and collagen synthesis in traumatic tendinopathy models in rabbit.

Plasma rich in growth factors versus corticosteroid injections for management of chronic rotator cuff tendinopathy: a prospective double-blind randomized controlled trial with 1 year of follow-up.

BACKGROUND: Rotator cuff tendinopathy (RCT) is a painful and dysfunctional shoulder condition traditionally considered as a degenerative pathology. However, evidence is pointing to immunocompetent cells and activated stromal fibroblasts as the drivers of a nonresolved inflammatory condition in RCT. As potent anti-inflammatory agents, corticosteroid injections have been among the first-line and the most common therapeutic strategies. Recently, another adjuvant therapy to treat musculoskeletal inflammation-driven painful conditions, namely, platelet-rich plasma (PRP), has emerged as safe and effective. The aim of this study was to compare the clinical efficacy of intratendinous injections of plasma rich in growth factors (PRGF) with conventional intratendinous corticosteroid injections on patients with chronic RCT using patient-reported outcome measures. METHODS: A total of 39 patients received PRGF treatment (3 infiltrations, 1 every other week), whereas 40 patients, as a control group, received corticosteroid (3 infiltrations, 1 every other week). Patients were evaluated before treatment and at 3, 6, and 12 months of follow-up using the University of California Los Angeles (UCLA) scale, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), and Constant test. The primary outcome of the study was a 15% superior improvement of the PRGF group compared with the corticosteroid group in the UCLA scale and QuickDASH test at 6 months of follow-up, considering this difference to be clinically relevant. RESULTS: Both PRGF and corticosteroid groups showed significant clinical improvement in the 3 scores at all time points of the study compared with baseline. However, at 6 and 12 months of follow-up, the PRGF group had 22.1% and 21.2% superior improvement of the UCLA test, 14.3% and 13.5% for QuickDASH, and 16.4% and 20.2% for the Constant-Murley test, respectively, compared to the corticosteroid group. CONCLUSIONS: Three PRGF intratendinous injections every other week in patients with chronic rotator cuff tendinopathy show significantly superior and sustained pain-relieving and functional improvements compared with corticosteroid intratendinous injections assessed by 3 patient-reported outcome scales at 6 and 12 months of follow-up.

Comparison of Extracorporeal Shock Wave Therapy and Ultrasound-Guided Shoulder Injection Therapy in Patients with Supraspinatus Tendinitis.

Background: The present study compared the clinical effect of extracorporeal shock wave therapy (ESWT) with that of ultrasound (US)-guided shoulder steroid injection therapy in patients with supraspinatus tendinitis. We hypothesized that the two treatments would show comparable results. Methods: The inclusion criteria were age over 20 years and diagnosis of supraspinatus tendinitis using US. Ultimately, 26 patients were assigned using blocked randomization: 13 in the US-guided shoulder injection group and 13 in the ESWT group. Treatment outcomes were evaluated using the pain visual analog scale (pVAS), the American Shoulder and Elbow Society (ASES) score, and the Constant score at baseline and at 1 and 3 months after the procedure. Results: At 1 month after the intervention, pVAS, ASES, and constant score were significantly higher in the US-guided shoulder injection group than in the ESWT group, but not at 3 months after the intervention. Both groups showed clinically significant treatment effects at 3 months after the intervention compared to baseline. No significance was shown using equivalence testing. Conclusions: US-guided shoulder injection therapy was not superior to ESWT therapy. Considering the complications and rebound phenomenon of steroid injections, interventions using ESWT may be a good alternative to treat patients with supraspinatus tendinitis.

SS-31 as a Mitochondrial Protectant in the Treatment of Tendinopathy: Evaluation in a Murine Supraspinatus Tendinopathy Model.

BACKGROUND: Prior studies have demonstrated mitochondrial dysfunction in tendinopathy. The objective of this investigation was to explore the potential of SS-31 (elamipretide), a mitochondrial protectant, to improve mitochondrial function and promote tendon healing in a murine supraspinatus tendinopathy model. METHODS: One hundred and twenty-six mice (252 limbs) were divided into 6 groups (42 limbs/group) that received (I) 4 weeks of impingement; (II) 8 weeks of impingement; (III) 8 weeks of impingement including 4 weeks of SS-31 treatment (5 mg/kg/d) starting after 4 weeks of impingement; (IV) 4 weeks of impingement ending with clip removal, followed by harvesting 4 weeks later; and (V) 4 weeks of impingement ending with clip removal, followed by 4 weeks of SS-31 treatment and harvesting; and a control group. Specimens were prepared for biomechanical testing, histological analysis, transmission electron microscopy, measurement of superoxidative dismutase (SOD) activity, and measurement of gene expression. RESULTS: Failure force decreased after impingement, compared with the intact tendon, and the decrease was partially reversed after clip removal, SS-31 treatment, and the 2 treatments combined. A similar pattern was observed for stiffness. Histological analysis demonstrated higher modified Bonar scores in the impingement groups; however, the changes in tendon morphology were partially reversed following all treatments, especially the combined treatment. Decreased mitochondrial number and altered organization and density of cristae were observed in the impingement groups. Mitochondrial structure and number became more normal, with improvement in morphology of the cristae, after clip removal and/or SS-31 treatment. SOD activity decreased after impingement, compared with the control group, then increased significantly again after treatment, especially in the combined treatment group. Mitochondria-related gene expression decreased in the impingement groups and increased again after treatment. CONCLUSIONS: The mitochondrial protectant SS-31 improved mitochondrial function, promoting tendon healing, especially when combined with removal of subacromial impingement. CLINICAL RELEVANCE: Improving mitochondrial function with agents such as SS-31 may represent an effective treatment to promote healing in the setting of supraspinatus tendinopathy.

Calcific tendinitis of the longus colli muscle. / Kalsifiserende tendinitt i m. longus colli.

BACKGROUND: Calcific tendinitis of the longus colli muscle is an aseptic inflammatory reaction to calcium hydroxyapatite crystal deposition in the cervical prevertebral space. CASE PRESENTATION: A 40-year-old woman presented with neck pain and odonyphagia. She had reduced mobility in her neck, tenderness to palpation and elevated CRP with normal leukocyte count and sedimentation rate. CT revealed a fluid collection in the retropharyngeal space and a calcific deposition in the longus colli muscle consistent with calcific tendinitis. She improved with NSAID therapy. Blood cultures taken on arrival showed no growth. INTERPRETATION: Acute calcific tendinitis of the longus colli muscle is an aseptic inflammatory process in the cervical prevertebral space and an important mimicker of retropharyngeal abscess and spondylodiscitis.

Acute Calcific Tendinitis of the Flexor Carpi Ulnaris Tendon Treated with Lavage and Steroid Injection: A Case Report.

Acute calcific tendinitis (ACT) is a relatively uncommon disorder that can involve the hand and wrist. ACT is frequently misdiagnosed due to a lack of familiarity with the condition and the clinical presentation that can be confused with other conditions. We report a case of acute calcific tendinitis of the flexor carpi ulnaris (FCU) tendon in a 68-year-old woman. She presented with acute left volar wrist pain, erythema, swelling, and restricted range of motion. Due to her inability to take nonsteroidal anti-inflammatory drugs (NSAIDs) and oral prednisone, she was treated with lavage and steroid injection of the calcified mass. Following the injection, there was dramatic improvement in her symptoms. Cortisone injection with lavage is an accepted treatment for rotator cuff calcific tendinitis and is another treatment option for ACT involving the hand and wrist.

Efectos de los antiinflamatorios no esteroideos en las tendinopatías / Effects of Non-Steroidal Anti-Inflammatory Drugs in Tendinopathies

Introducción: Los antiinflamatorios no esteroideos son comúnmente usados para el tratamiento de las tendinopatías, pero la evidencia sobre este tratamiento es escasa. Objetivo: Realizar una revisión sistemática acerca de los efectos de los en las tendinopatías. Métodos: Se desarrolló una búsqueda bibliográfica en PubMed, WOS, PEDro, Medline, Cinahl y SPORTDiscus. Se incluyeron un total de 13 ensayos clínicos con una calidad metodológica media de 7,15/10 en la escala PEDro. Conclusiones: En la mayoría de los artículos se observó una mejoría corto plazo en el dolor y la funcionalidad con el uso de AINEs. Los ensayos clínicos incluidos no analizaron la presencia de inflamación en esta patología. Se necesitan más estudios que determinen la función de la inflamación en la tendinopatía que justifique el uso de los antiinflamatorios no esteroideos(AU)

Introduction: Non-steroidal anti-inflammatory drugs are commonly used for the treatment of tendinopathies, but the evidence on this treatment is scarce. Objective: To carry out a systematic review about the effects of non-steroidal anti-inflammatory drugs in tendinopathies. Methods: A bibliographic search was carried out in PubMed, WOS, PEDro, Medline, Cinahl and SPORTDiscus. A total of 13 clinical trials with a mean methodological quality of 7.15/10 on the PEDro scale were included. Conclusions: In most of the articles, a short-term improvement in pain and functionality was observed with the use of non-steroidal anti-inflammatory drugs. The clinical trials included did not analyze the presence of inflammation in this pathology. More studies are needed to determine the role of inflammation in tendinopathy that justifies the use of nonsteroidal anti-inflammatory drugs(AU)

Modulation of Inflammation by Plant-Derived Nutraceuticals in Tendinitis.

Tendinitis (tendinopathy) is a pro-inflammatory and painful tendon disease commonly linked with mechanical overuse and associated injuries, drug abuse, and lifestyle factors (including poor diet and physical inactivity) that causes significant healthcare expenditures due to its high incidence. Nuclear factor kappa B (NF-κB) is one of the major pro-inflammatory transcription factors, along with other inflammation signaling pathways, triggered by a variety of stimuli, including cytokines, endotoxins, physical and chemical stressors, hypoxia, and other pro-inflammatory factors. Their activation is known to regulate the expression of a multitude of genes involved in inflammation, degradation, and cell death. The pathogenesis of tendinitis is still poorly understood, whereas efficient and sustainable treatment is missing. Targeting drug suppression of the key inflammatory regulators represents an effective strategy for tendinitis therapy, but requires a comprehensive understanding of their principles of action. Conventional monotherapies are often ineffective and associated with severe side effects in patients. Therefore, agents that modulate multiple cellular targets represent therapeutic treatment potential. Plant-derived nutraceuticals have been shown to act as multi-targeting agents against tendinitis via various anti-oxidant and anti-inflammatory mechanisms, whereat they were able to specifically modulate numerous signaling pathways, including NF-κB, p38/MAPK, JNK/STAT3, and PI3K/Akt, thus down-regulating inflammatory processes. This review discusses the utility of herbal nutraceuticals that have demonstrated safety and tolerability as anti-inflammatory agents for the prevention and treatment of tendinitis through the suppression of catabolic signaling pathways. Limitations associated with the use of nutraceuticals are also described.

Friedelin Alleviates the Pathogenesis of Collagenase-Induced Tendinopathy in Mice by Promoting the Selective Autophagic Degradation of p65.

With the development of an aging population, tendinopathy has become a common musculoskeletal disease in the elderly with a high recurrence rate and no curative treatment. The inflammation mediated by NF-κB signaling plays an important role in tendon senescence and degeneration. Friedelin (FR) is a triterpenoid derived from green plants, which has a variety of pharmacological functions, such as analgesia, anti-inflammation, antioxidation, and anti-tumor functions. However, the role and mechanism of FR in tendinopathy are unclear. Here, we found that FR improved the mechanical strength of the Achilles tendon, restored the orderly arrangement of collagen fibers, reduced inflammatory cell infiltration, and promoted tenogenesis, thereby blocking the progression of tendinopathy. Mechanistically, FR promoted the autophagic degradation of p65 by enhancing the interaction between p62 and p65 and effectively inhibited the activation of the NF-κB pathway, thus alleviating the inflammatory response of tenocytes. In addition, FR recruited E3 ubiquitin enzyme RNF182 to increase the K48-linked ubiquitination of p65 and promoted p62-mediated autophagic degradation. Furthermore, blocking ubiquitination reversed the degradation of p65 by FR. Therefore, these findings identify the new pharmacological mechanism of the anti-inflammatory effect of FR and provide a new candidate drug for the treatment of tendinopathy.

17ß-Estradiol attenuates inflammation and tendon degeneration in a rat model of Achilles tendinitis.

INTRODUCTION: 17ß-Estradiol (E2) is an immune-regulatory agent with anti-inflammatory effects. However, it is still unknown whether E2 exerts pharmacological properties against Achilles tendinitis (AT). This study aims to investigate the effects of E2 on AT and its underlying mechanisms. MATERIALS AND METHODS: The established model of Achilles tendinitis was intraperitoneally injected with E2 (10, 20, or 30 µg/kg/d). After 8 weeks, biomechanical properties of the Achilles tendon were determined. Hydroxyproline content and tendon degeneration-related biomarkers were determined. The levels of inflammatory cytokines and apoptotic-related biomarkers in tendon tissues were determined. Furthermore, western blotting was determined to detect the expressions of ER-α and the PI3K/Akt pathway in tendon tissues. RESULTS: E2 relieved AT-related symptoms in a dose-dependent manner. E2 ameliorated tendon degeneration by regulating tendon degeneration-related biomarkers (e.g. collagen types I and III, Decorin (DCN), and tenascin-C). Besides, treatment with E2 suppressed inflammatory cytokines and increased anti-inflammatory cytokines. Treatment with E2 also regulated cell apoptosis in tendon tissues. The underlying mechanism study revealed that treatment with E2 activated ER-α and upregulated the PI3K/Akt pathway. CONCLUSION: The regulatory effects of E2 on inflammation and tendon degeneration in a rat model of AT were associated with the ER-α and the PI3K/Akt signaling pathways.

Long-term anti-inflammatory effects of injectable celecoxib nanoparticle hydrogels for Achilles tendon regeneration.

The treatment of chronic Achilles tendonitis (AT) often requires prolonged therapy and invasive therapeutic methods such as surgery or therapeutic endoscopy. To prevent the progression of chronic AT, excessive inflammation must be alleviated at an early stage. Corticosteroids or nonsteroidal anti-inflammatory drugs are generally prescribed to control inflammation; however, the high doses and long therapeutic periods required may lead to serious side effects. Herein, a local injectable poly(organophosphazene) (PPZ) - celecoxib (CXB) nanoparticle (PCNP) hydrogel system with long-term anti-inflammatory effects was developed for the treatment of tendonitis. The amphiphilic structure and thermosensitive mechanical properties of PPZ means that the hydrophobic CXB can be easily incorporated into the hydrophobic core to form PCNP at 4 °C. Following the injection of PCNP into the AT, PCNP hydrogel formed at body temperature and induced long-term local anti-inflammatory effects via sustained release of the PCNP. The therapeutic effects of the injectable PCNP system can alleviate excessive inflammation during the early stages of tissue damage and boost tissue regeneration. This study suggests that PCNP has significant potential as a long-term anti-inflammatory agent through sustained nonsteroidal anti-inflammatory drugs (NSAIDs) delivery and tissue regeneration boosting. STATEMENT OF SIGNIFICANCE: In the treatment of Achilles tendinitis, a long-term anti-inflammatory effect is needed to alleviate excessive inflammation and induce regeneration of the damaged Achilles tendon. Injectable poly(organophosphazene)(PPZ)-celecoxib(CXB) nanoparticles (PCNP) generated a long-term, localized-anti-inflammatory effect in the injected region, which successfully induced the expression of anti-inflammatory cytokines and suppressed pro-inflammatory cytokines, while the PCNPs degraded completely. Accordingly, regeneration of the damaged Achilles tendon was achieved through the long-term anti-inflammatory effect induced by a single PCNP injection. The PCNP system therefore has great potential in long-term NSAIDs delivery for various tissue engineering applications.

Acute Calcific Tendinitis of the Longus Colli: Not All Retropharyngeal Fluid is an Abscess.

OBJECTIVE: This report aimed to present a case of acute calcific tendinitis of the longus colli muscle as an uncommon cause of neck pain and dysphagia and is often misdiagnosed as a retropharyngeal abscess. METHODS: Case report and literature review. RESULTS: Acute calcific tendinitis is often misdiagnosed as a retropharyngeal abscess; however, it is distinguished from the latter based on patient history and unique radiologic findings. History, examination, and laboratory findings do not suggest an infectious etiology, and radiographic findings include a non-rim-enhancing fluid collection with or without calcifications anterior to the upper cervical spine. CONCLUSION: Unlike retropharyngeal abscess, acute calcific tendinitis is managed conservatively. When consulted for a possible retropharyngeal abscess, the otolaryngologist should avoid anchoring bias by independently obtaining a detailed history and examination and personally reviewing radiologic images to avoid unnecessary intervention.