Ethnobotany and phytochemistry of plants used to treat musculoskeletal disorders among Skaw Karen, Thailand.

CONTEXT: Musculoskeletal system disorders (MSD) are prevalent around the world affecting the health of people, especially farmers who work hard in the field. Karen farmers use many medicinal plants to treat MSD. OBJECTIVE: This study collects traditional plant-based remedies used by the Skaw Karen to treat MSD and evaluates their active phytochemical compounds. MATERIALS AND METHODS: The ethnobotanical study was conducted in six Karen villages in Chiang Mai province using semi-structured interviews were of 120 informants. The data were analyzed using ethnobotanical indices including use values (UV), choice value (CV), and informant consensus factor (ICF). Consequently, the 20 most important species, according to the indices, were selected for phytochemical analysis using LC-MS/MS. RESULTS: A total of 3731 use reports were obtained for 139 species used in MSD treatment. The most common ailments treated with those plants were muscular pain. A total of 172 high-potential active compounds for MSD treatment were identified. Most of them were flavonoids, terpenoids, alkaloids, and steroids. The prevalent phytochemical compounds related to treat MSD were 9-hydroxycalabaxanthone, dihydrovaltrate, morroniside, isoacteoside, lithocholic acid, pomiferin, cucurbitacin E, leonuriside A, liriodendrin, and physalin E. Sambucus javanica Reinw. ex Blume (Adoxaceae), Betula alnoides Buch.-Ham. ex D.Don (Betulaceae), Blumea balsamifera (L.) DC. (Asteraceae), Plantago major L. (Plantaginaceae) and Flacourtia jangomas (Lour.) Raeusch. (Salicaceae) all had high ethnobotanical index values and many active compounds. DISCUSSION AND CONCLUSIONS: This study provides valuable information, demonstrating low-cost medicine plants that are locally available. It is a choice of treatment for people living in remote areas.

Curcumin nanoparticles and the therapeutic potential of curcumin for musculoskeletal disorders.

Musculoskeletal disorders (MSD) are a collection of degenerative conditions impacting the body's bones, joints, muscles, tendons, ligaments, and nerves. MSDs affect approximately 1.71 billion individuals worldwide and are a significant cause of disability. Curcumin is a polyphenolic compound with anti-inflammatory, antioxidant, and antitumor properties. In this review, we will discuss the research progress of structural analogs, derivatives, and nanomaterials that can improve the bioavailability of this natural drug. Curcumin may potentially retard the progression of osteoporosis, osteoarthritis, and rheumatoid arthritis. These effects may be related to curcumin's targeting of multiple signalling pathways.

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.

Oxygen-Ozone Therapy in the Rehabilitation Field: State of the Art on Mechanisms of Action, Safety and Effectiveness in Patients with Musculoskeletal Disorders.

In recent years, the interest in oxygen-ozone (O2O3) therapy application has considerably increased in the field of rehabilitation. Despite its widespread use in common clinical practice, the biochemical effects of O2O3 are still far from being understood, although its chemical properties seem to play a pivotal role in exerting its positive effects on different pathological conditions. Indeed, the effectiveness of O2O3 therapy might be partly due to the moderate oxidative stress produced by O3 interactions with biological components. O2O3 therapy is widely used as an adjuvant therapeutic option in several pathological conditions characterized by chronic inflammatory processes and immune over-activation, and most musculoskeletal disorders share these pathophysiological processes. The present comprehensive review depicts the state-of-the-art on the mechanisms of action, safety and effectiveness of O2O3 therapy in the complex scenario of the management of musculoskeletal disorders. Taken together, our findings suggest that O2O3 therapy seems to reduce pain and improve functioning in patients affected by low back pain and knee osteoarthritis, as reported by several studies in the literature. However, to date, further studies are warranted to clearly investigate the therapeutic effects of this promising therapy on other musculoskeletal disorders in the field of rehabilitation.

Evaluation of Virola oleifera activity in musculoskeletal pathologies: Inhibition of human multiple myeloma cells proliferation and combination therapy with dexamethasone or bortezomib.

ETHNOPHARMACOLOGICAL RELEVANCE: Virola oleifera (Schott) A.C. Smith, Myristicaceae, has been widely used in traditional medicine in Brazil to treat rheumatic pain, joint tumours, skin diseases, halitosis, bronchial asthma, haemorrhoids, and intestinal worms. Recently, research data showed the antioxidant properties in several oxidative stress-related models. However, there is no experimental evidence supporting its potential use in managing rheumatic diseases and bone malignancies. AIMS OF THE STUDY: To evaluate the therapeutic potential of the resin from Virola oleifera in joint and bone diseases, namely arthritis, osteosarcoma, chondrosarcoma, and multiple myeloma. MATERIALS AND METHODS: To determine Virola oleifera resin (VO) effects on arthritis-associated inflammation and cartilage degradation, the LPS-induced NO production, and mRNA and protein expression of ADAMTS5, MMP13, COL2, and ACAN, were evaluated in chondrocytes (ATDC5 and TC28 cell lines). The cytotoxic effects of VO (0.05-50 µg/ml) on multiple myeloma (ARH-77), osteosarcoma (SAOS-2), and chondrosarcoma (SW-1353) cell lines were analysed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The VO effects, combined with dexamethasone or bortezomib, were evaluated in a multiple myeloma cell line. The mechanisms of VO, alone or in combination with bortezomib, were determined by cell cycle analysis through flow cytometry, while expression levels of p-Akt/Akt, p-ERK/ERK, p-p38/p38 MAPK, Bax, Bcl-2, and cleaved-caspase-3/caspase-3 proteins by Western blot. RESULTS: VO had no significant effect on LPS-induced NO production in chondrocytes at non-cytotoxic concentrations. VO treatment diminished the mRNA levels of metalloproteinases and ECM components; however, any significant effect was observed on the protein expression levels. The cell viability of a multiple myeloma cell line was strongly reduced by VO treatment in a dose- and time-dependent manner, while osteosarcoma and chondrosarcoma cell lines viability was significantly affected only by the highest dose assessed. In multiple myeloma cells, VO leads to G2/M cell cycle arrest. Furthermore, it synergizes with dexamethasone by increasing cell toxicity. Finally, VO reverts bortezomib activity by counteracting ERK1/2, Bax, and caspase-3 activation. CONCLUSIONS: The current work supports the ethnopharmacological use of Virola oleifera (Schott) A.C. Smith in bone and joint diseases, but there is no evidence for the amelioration of arthritis-associated inflammatory or catabolic processes. Our data also supports the potential use of Virola oleifera as adjuvant therapy to optimize the pharmacologic effects of current chemotherapeutic drugs. However, possible herb-drug interactions should be considered before clinical application.

l-Cysteine and Vitamin D Co-Supplementation Alleviates Markers of Musculoskeletal Disorders in Vitamin D-Deficient High-Fat Diet-Fed Mice.

Vitamin D (VD) deficiency is associated with musculoskeletal disorders. This study examines whether co-supplementation of l-cysteine (LC) and VD is better than monotherapy with LC or VD at alleviating musculoskeletal dyshomeostasis in the skeletal muscle of VD-deficient high-fat diet (HFD-VD-) fed mice. Mice were fed a healthy diet or an HFD; for VD-deficient animals, the mice were maintained on a HFD-VD-diet (16 weeks); after the first 8 weeks, the HFD-VD-diet-fed mice were supplemented for another 8 weeks with LC, VD-alone, or the same doses of LC + VD by oral gavage. Saline and olive oil served as controls. Myotubes were exposed with high-glucose, palmitate, Monocyte Chemoattractant Protein 1 (MCP-1), and Tumor Necrosis Factor (TNF), to mimic the in vivo microenvironment. In vitro deficiencies of glutathione and hydrogen sulfide were induced by knockdown of GCLC and CSE genes. Relative gene expression of biomarkers (myogenic: MyoD, Mef2c, Csrp3; muscle dystrophy: Atrogin1, Murf1, and Myostatin; bone modeling and remodeling: RANK, RANKL, OPG) were analyzed using qRT-PCR. Co-supplementatoin with LC + VD showed beneficial effects on gene expression of myogenic markers and OPG but reduced markers of dystrophy, RANK/RANKL in comparison to LC or VD alone-supplementation. In vitro myotubes treated with glutathione (GSH) precursors also showed a positive effect on OPG and the myogenesis genes, and inhibited RANK/RANKL and muscle-dystrophy markers. This study reveals that the co-supplementation of LC with VD significantly alleviates the markers of musculoskeletal disorders in the skeletal muscle better than monotherapy with LC or VD in HFD-VD-fed mice.

Attitudes, beliefs, and practices among Swiss chiropractors regarding medication prescribing for musculoskeletal conditions: a national Q-methodology study.

BACKGROUND: Swiss chiropractors have been licensed since 1995 to prescribe from a limited formulary of medications for treating musculoskeletal (MSK) conditions. In January 2018, this formulary was expanded to include additional muscle relaxant, analgesic, and anti-inflammatory medications. Internationally, controversy remains over whether or not medication prescribing should be pursued within the chiropractic profession. OBJECTIVE: The purpose of this study was to assess Swiss chiropractors' attitudes, beliefs, and practices regarding their existing medication prescription privileges. This information will provide new insights on the topic and help inform research and policy discussions about expanding chiropractic prescription rights in other jurisdictions. METHODS: A 13-item questionnaire and Q-methodology approach were used to conduct the assessment. Recruitment was conducted by e-mail between December 2019 and February 2020, and all members of the Swiss Chiropractic Association were eligible to participate. Data were analyzed using by-person factor analysis and descriptive statistics. RESULTS: In total, 187 Swiss chiropractors participated in this study (65.4% response rate). Respondents reported prescribing analgesics, anti-inflammatories, and muscle relaxants to a median of 5, 5, and 0% of patients, respectively. Forty-two percent of respondents expressed interest in further expanding the range of current medications available to Swiss chiropractors for treating MSK conditions. Only 15% expressed interest in expanding this range to include medications for treating non-MSK conditions. In the Q-methodology analysis, four salient viewpoints/groups regarding medication prescribing emerged: prescribers, non-prescribers, collaborators, and integrators. All except non-prescribers thought medication prescription privileges were advantageous for the chiropractic profession in Switzerland. There was also strong consensus among all four groups that medication prescribing should not replace manual therapy in chiropractic practice. CONCLUSION: This was the first national survey on attitudes toward prescribing medications among Swiss chiropractors since the year 2000, and the first using Q-methodology. With this approach, four unique groups of chiropractic prescribers were identified. Even with diversity among clinicians, the findings of this study showed general support for, along with conservative use of, prescribing privileges within the Swiss chiropractic profession. Studies in jurisdictions outside of Switzerland are needed to assess whether chiropractors are interested in expanding their scopes of practice to include similar prescribing privileges.

Medicinal Cannabis in Orthopaedic Practice.

Cannabis has gained widespread public advocacy since its legalization in several states with recent evidence suggesting that its self-reported use has increased in patients undergoing a primary total joint arthroplasty. The endocannabinoid system has been proposed to play a role in decreasing the inflammatory cascade and enhancing pain management. For these reasons, interest has emerged in the orthopaedic community as a potential treatment or adjunct to treatment in many musculoskeletal conditions. However, the evidence to date is scant and precludes recommendations for its widespread use. Given the current paucity of evidence in the orthopaedic cohort, future research is warranted in this area to determine the efficacy and safety before endorsements can be made by orthopaedic surgeons.

Berberine and musculoskeletal disorders: The therapeutic potential and underlying molecular mechanisms.

BACKGROUND: Musculoskeletal disorders are a group of disorders that affect the joints, bones, and muscles, causing long-term disability. Berberine, an isoquinoline alkaloid, has been previously established to exhibit beneficial properties in preventing various diseases, including musculoskeletal disorders. PURPOSE: This review article aims to recapitulate the therapeutic potential of berberine and its mechanism of action in treating musculoskeletal disorders. METHODS: A wide range of literature illustrating the effects of berberine in ameliorating musculoskeletal disorders was retrieved from online electronic databases (PubMed and Medline) and reviewed. RESULTS: Berberine may potentially retard the progression of osteoporosis, osteoarthritis and rheumatoid arthritis. Limited studies reported the effects of berberine in suppressing the proliferation of osteosarcoma cells. These beneficial properties of berberine are mediated in part through its ability to target multiple signaling pathways, including PKA, p38 MAPK, Wnt/ß-catenin, AMPK, RANK/RANKL/OPG, PI3K/Akt, NFAT, NF-κB, Hedgehog, and oxidative stress signaling. In addition, berberine exhibited anti-apoptotic, anti-inflammatory, and immunosuppressive properties. CONCLUSION: The current evidence indicates that berberine may be effective in preventing musculoskeletal disorders. However, findings from in vitro and in vivo investigations await further validation from human clinical trial.

Symphytum Species: A Comprehensive Review on Chemical Composition, Food Applications and Phytopharmacology.

Symphytum species belongs to the Boraginaceae family and have been used for centuries for bone breakages, sprains and rheumatism, liver problems, gastritis, ulcers, skin problems, joint pain and contusions, wounds, gout, hematomas and thrombophlebitis. Considering the innumerable potentialities of the Symphytum species and their widespread use in the world, it is extremely important to provide data compiling the available literature to identify the areas of intense research and the main gaps in order to design future studies. The present review aims at summarizing the main data on the therapeutic indications of the Symphytum species based on the current evidence, also emphasizing data on both the efficacy and adverse effects. The present review was carried out by consulting PubMed (Medline), Web of Science, Embase, Scopus, Cochrane Database, Science Direct and Google Scholar (as a search engine) databases to retrieve the most updated articles on this topic. All articles were carefully analyzed by the authors to assess their strengths and weaknesses, and to select the most useful ones for the purpose of review, prioritizing articles published from 1956 to 2018. The pharmacological effects of the Symphytum species are attributed to several chemical compounds, among them allantoin, phenolic compounds, glycopeptides, polysaccharides and some toxic pyrrolizidine alkaloids. Not less important to highlight are the risks associated with its use. In fact, there is increasing consumption of over-the-counter drugs, which when associated with conventional drugs can cause serious and even fatal adverse events. Although clinical trials sustain the folk topical application of Symphytum species in musculoskeletal and blunt injuries, with minor adverse effects, its antimicrobial potency was still poorly investigated. Further studies are needed to assess the antimicrobial spectrum of Symphytum species and to characterize the active molecules both in vitro and in vivo.

Platelet-Rich Fibrin and its Emerging Therapeutic Benefits for Musculoskeletal Injury Treatment.

New therapies that accelerate musculoskeletal tissue recovery are highly desirable. Platelet-rich fibrin (PRF) is a leukocyte- and platelet-rich fibrin biomaterial that acts as a binding site for both platelets and growth factors. Through increasing the local concentration of growth factors at specific tissues, PRF promotes tissue regeneration. PRF has been frequently used in combination with bone graft materials to reduce healing times and promote bone regeneration during maxillofacial surgery. However, its benefits during muscle repair and recovery are less well-documented. Here, we perform a narrative review on PRF therapies and muscle injuries to ascertain its beneficial effects. We reviewed the factors that contribute to the biological activity of PRF and the published pre-clinical and clinical evidence to support its emerging use in musculoskeletal therapy. We include in vitro studies, in vivo animal studies and clinical articles highlighting both the success and failures of PRF treatment. PRF can promote the healing process when used in a range of orthopaedic and sports-related injuries. These include cartilage repair, rotator cuff surgery and anterior cruciate ligament surgery. However, conflicting data for these benefits have been reported, most likely due to inconsistencies in both PRF preparation protocols and dosing regimens. Despite this, the literature generally supports the use of PRF as a beneficial adjuvant for a range of chronic muscle, tendon, bone or other soft tissue injuries. Further clinical trials to confirm these benefits require consistency in PRF preparation and the classification of a successful clinical outcome to fully harness its potential.

Ultrasonography for oxygen-ozone therapy in musculoskeletal diseases.

Over the years, infiltrative oxygen-ozone therapy has shown clinical benefits in several musculoskeletal disorders, due to its potential analgesic, anti-inflammatory, antioxidant and immunomodulatory effect. Ultrasonography is a safe, non-invasive imaging, easily available, and has the additional advantage of being real time for imaging and image-guided procedures of the musculoskeletal system. This review explains the numerous promising ways in which ultrasonography can be useful in oxygen-ozone therapeutic practices for musculoskeletal disorders, in order to improve safety and accuracy of treatment.

Musculoskeletal Therapies: Musculoskeletal Injection Therapy.

Injections often are used in the management of common musculoskeletal conditions. Physicians should understand the disease pathophysiology and evidence supporting available injections when determining appropriate therapy. These therapies include corticosteroid injections (CSIs), hyaluronic acid (HA) injections, hypertonic dextrose prolotherapy, platelet-rich plasma (PRP) injections, mesenchymal stem cell (MSC) injections, and trigger point injections (TPIs). CSIs are recommended conditionally by the American College of Rheumatology for osteoarthritis (OA) management. CSIs are associated with short-term improvement in pain and function in patients with OA, although cartilage volume loss can occur with repetitive, frequent use. CSIs show no long-term benefit in the management of lateral epicondyle pain. For knee OA, HA injection shows prolonged improvement of pain and function compared with CSI. Studies of HA injection for other joints show the injection to be no more effective than placebo. Evidence for prolotherapy and PRP injection shows long-term improvement of pain and function in knee OA and tendinopathies. There is low-quality evidence showing MSC injections improve pain and function in OA and tendinopathies. It is unclear whether TPIs are effective because of a lack of high-quality evidence. Ultrasonography guidance has been shown to improve accuracy of delivery and clinical outcomes in injection therapies.

Single arm phase II study of oral vitamin B12 for the treatment of musculoskeletal symptoms associated with aromatase inhibitors in women with early stage breast cancer.

Breast cancer patients receiving endocrine therapy with aromatase Inhibitors (AIs) often experience musculoskeletal and joint-related side effects. The purpose of this study was to evaluate the effect of Vitamin B12 supplements on musculoskeletal symptoms such as pain and arthralgias induced by AIs and to correlate response with serum and inflammatory biomarkers. Upon receiving approval by the Institutional Review Board (IRB), the majority of the patients consented into the study were treated at the Texas Tech Breast Care Center. Included were patients who had a diagnosis of invasive breast cancer (Stages I-III), and were experiencing significant musculoskeletal symptoms associated to AIs. Only patients with an average pain score ≥ 4, as assessed by the Brief Pain Inventory-Short Form (BPI-SF) questionnaire, were included in the study. Participants received 2500 mcg of sublingual vitamin B12 daily for 90 days. Assessments at baseline and at 3 months included: BPI-SF pain scores, the impact on quality of life determined by Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES), and correlative serum markers relative to baseline (a pre-post study). A total of forty-one patients were enrolled. Average pain scores were improved by 34% (P < .0001) at 3 months compared to baseline. In addition, a 23% improvement in worst pain was noted (P = .0003). Analysis of the results for the FACT-ES scoring showed improvement on all scales. No significant adverse events were observed. Decrease in pain score was correlated with increased serum B12 levels. This study suggests that Vitamin B12 reduces pain and improves quality of life for patients taking AIs who experienced AI-related musculoskeletal symptoms. If confirmed in large randomized prospective trials, Vitamin B12 would be a safe and cost-effective option for the treatment of AI-related musculoskeletal symptoms.

Ascorbic Acid and Its Clinical Role in Orthopaedic Surgery.

Ascorbic acid (vitamin C) is an essential micronutrient with evidence supporting its role in bone formation, tissue repair, and collagen production. Its clinical importance to the field of orthopaedic surgery has yet to be fully defined. Several observational studies have shown improved bone density and reduced hip fracture risk with supplementation. Its effect on bone fracture and soft tissue injury has been promising in animal models, but is not adequately studied in human trials. Results have been mixed concerning its role in chondroprotection and osteoarthritis treatment. Evidence suggesting reduced incidence of complex regional pain syndrome following distal radius fracture when treated with adjuvant ascorbic acid has prompted much debate but has received an endorsement of moderate support from the American Academy of Orthopaedic Surgeons. Given its potential benefits, low cost, and safety profile, ascorbic acid supplementation warrants consideration by orthopaedic surgeons in the treatment of a variety of musculoskeletal injuries (Journal of Surgical Orthopaedic Advances 27(4):261-268, 2018).

A novel boswellic acids delivery form (Casperome®) in the management of musculoskeletal disorders: a review.

Standard pharmacological treatment of musculoskeletal conditions is often associated with relevant side effects. Botanical preparations endowed with a good tolerability profile, therefore, could have a role in the management of these disorders. Among different natural products, Boswellia serrata extracts have long been used for the treatment of musculoskeletal disorders, given their marked anti-inflammatory activity and their ability to promote tissue regeneration. However, standard preparations of Boswellia serrata show overall modest pharmacokinetic properties, a limitation which may ultimately lead to reduced efficacy. In an effort to improve the pharmacokinetic properties, Casperome®, a lecithin-based formulation of Boswellia serrata extract representing the whole natural bouquet, has been developed. This formulation was effective in the treatment of Achilles tendonitis, epicondylitis, radiculopathies, ankle sprains and sport injuries as shown in several clinical studies, the majority of which with a randomized design and all evaluating a number of well-recognized parameters of efficacy for the therapy of musculoskeletal disorder. All studies were consistent in showing a prompt decrease of pain and improvement of functionality of the affected area after supplementation with Casperome®, without any relevant adverse effect. Remarkably, these symptomatic improvements were paralleled by reduced plasmatic levels of inflammatory markers and by a diminished need for rescue analgesics. On these bases, Casperome® may have a role in the treatment of musculoskeletal disorders. Clinical studies in other similar conditions (e.g., osteoarthritis) appear warranted to further investigate the efficacy of this botanical product in more specific settings.

Oral Supplementation of Melatonin Protects against Fibromyalgia-Related Skeletal Muscle Alterations in Reserpine-Induced Myalgia Rats.

Fibromyalgia is a chronic syndrome characterized by widespread musculoskeletal pain and an extensive array of other symptoms including disordered sleep, fatigue, depression and anxiety. Important factors involved in the pathogenic process of fibromyalgia are inflammation and oxidative stress, suggesting that ant-inflammatory and/or antioxidant supplementation might be effective in the management and modulation of this syndrome. Recent evidence suggests that melatonin may be suitable for this purpose due to its well known ant-inflammatory, antioxidant and analgesic effects. Thus, in the current study, the effects of the oral supplementation of melatonin against fibromyalgia-related skeletal muscle alterations were evaluated. In detail, 90 Sprague Dawley rats were randomly treated with reserpine, to reproduce the pathogenic process of fibromyalgia and thereafter they received melatonin. The animals treated with reserpine showed moderate alterations at hind limb skeletal muscles level and had difficulty in moving, together with significant morphological and ultrastructural alterations and expression of inflammatory and oxidative stress markers in the gastrocnemius muscle. Interestingly, melatonin, dose and/or time dependently, reduced the difficulties in spontaneous motor activity and the musculoskeletal morphostructural, inflammatory, and oxidative stress alterations. This study suggests that melatonin in vivo may be an effective tool in the management of fibromyalgia-related musculoskeletal morphofunctional damage.

Energy-triggered drug release from polymer nanoparticles for orthopedic applications.

Sequestra, present in many cancers and orthopedic infections, provide a safe harbor for the development of drug resistance. In the face of burgeoning drug resistance, the importance of nanoscale, microenvironment-triggered drug delivery cannot be overestimated. Such strategies may preserve pharmaceutical efficacy and significantly alter the etiology of many orthopedic diseases. Although temperature-, pH- and redox-responsive nanoparticle-based systems have been extensively studied, local drug delivery from polymeric nanoparticles can be triggered by a variety of energy forms. This review offers an overview of the state of the field as well as a perspective on the safety and efficacy of ultrasound, hyperthermia and radio frequency-triggered internal delivery systems in a variety of applications.

Cannabinoids in the Management of Musculoskeletal or Rheumatic Diseases.

The endocannabinoid system impacts pain and inflammation with potential for therapeutic effect on patients with rheumatic diseases. The current treatment options include the herbal product derived from the plant Cannabis sativa, as well as pharmaceutical preparations. The legalization of medicinal cannabis (marijuana) in many jurisdictions and widespread public advocacy has propelled an interest in use either by prescription or self-medication. In this review, we examine current evidence for efficacy and adverse effects of any cannabinoid product in rheumatic conditions. The evidence to date is scant and precludes making recommendations for the use of cannabinoid preparations in rheumatology patients. In particular, the risks of herbal cannabis in patients are not well defined. Anecdote and advocacy cannot supersede sound evidence.