Immunometabolic Modulatory Role of Naltrexone in BV-2 Microglia Cells

Naltrexone is an opioid receptor antagonist commonly used to treat opioid and alcohol dependence. The use of low dose naltrexone (LDN) was found to have anti-inflammatory properties for treatment of diseases such as fibromyalgia, Crohn’s disease, multiple sclerosis and regional pain syndromes. Related to its anti-neuroinflammatory properties, the mechanism of action is possibly mediated via Toll-like receptor 4 antagonism, which is widely expressed on microglial cells. The aim of the present study was to assess the immunometabolic effects of naltrexone on microglia cells in in vitro conditions. Methods: All experiments were performed in the BV-2 microglial cell line. The cells were treated with naltrexone at 100 μM concentrations corresponding to low dose for 24 h. Cell viability was assessed for every drug dose. To induce additional activation, the cells were pretreated with LPS and IFN-γ. Immunofluorescence was used to analyse the classical microglial activation markers iNOS and CD206, while Seahorse was used for real-time cellular metabolic assessments. mTOR activity measured over the expression of a major direct downstream target S6K was assessed using western blot. Results: LDN induced a shift from highly activated pro-inflammatory phenotype (iNOShighCD206low) to quiescent anti-inflammatory M2 phenotype (iNOSlowCD206high) in BV-2 microglia cells. Changes in the inflammatory profile were accompanied by cellular metabolic switching based on the transition from high glycolysis to mitochondrial oxidative phosphorylation (OXPHOS). LDN-treated cells were able to maintain a metabolically suppressive phenotype by supporting OXPHOS with high oxygen consumption, and also maintain a lower energetic state due to lower lactate production. The metabolic shift induced by transition from glycolysis to mitochondrial oxidative metabolism was more prominent in cells pretreated with immunometabolic modulators such as LPS and IFN-γ. In a dose-dependent manner, naltrexone also modulated mTOR/S6K expression, which underlies the cell metabolic phenotype regulating microglia immune properties and adaptation. Conclusion: By modulating the phenotypic features by metabolic switching of activated microglia, naltrexone was found to be an effective and powerful tool for immunometabolic reprogramming and could be a promising novel treatment for various neuroinflammatory conditions.

Alien hand and complex regional pain syndromes during rehabilitation program

Introduction: Alien hand syndrome (AHS) belongs to the group of asymmetrical movement symptoms that are a characteristic picture of neurodegenerative diseases such as corticobasal degeneration syndrome (CBS). Changes in the musculoskeletal system such as dystonia, bradykinesia and myoclonus may also occur in the subacute stage of complex regional pain syndrome (CRPS) type I. Aim: To learn about difficulties related to diagnosis and rehabilitation of a patient with AHS and CRPS type I complicated by an upper limb fracture. Case study: A case of a patient admitted to the rehabilitation department with compulsive unilateral involuntary groping and grasping movements of the left hand for about half a year is presented. The woman has been suspected of CBS. A few months after the diagnosis, the patient was admitted to the rehabilitation ward, where she suffered an elbow fracture during exercise. Two months after fracture, type I CRPS was diagnosed. Results and discussion: AHS in CBS and CRPS type I may have a similar clinical picture, which makes differentiation difficult. It is very rare that both diseases coexist with each other. They can also lead to a number of unwanted symptoms such as limb fractures. Conclusions: CRPS may increase the symptoms of dystonia due to other causes. Patients with AHS and dystonia are more likely to break because of rapid movements alone or because of immobilization and osteoporotic changes. As a result, treatment and rehabilitation cannot be based on a questionable diagnosis of a neurological syndrome.

Trauma

This chapter in the Oxford Handbook of Clinical Specialties explores trauma. It looks at describing an X-ray and whether a patient needs an X-ray or computed tomography scan. It discusses management and complications of fractures as well as complex regional pain syndromes. It explores trauma to the arm, shoulder, elbow, and forearm, as well as distal radial and ulnar fractures, and hand fractures and injuries. It reviews proximal femoral fractures and hip fractures in the elderly, as well as injuries to the knee, and ankle and foot strains and fractures. It describes injuries to the face, neck, and eye, as well as nerve injury, including testing peripheral nerve motor functions, dermatomes and peripheral nerves, nerve compression and syndromes, injuries to the brachial plexus, and spinal cord injury.

Myofascial Pain Syndrome: A Concise Update on Clinical, Diagnostic and Integrative and Alternative Therapeutic Perspectives

Background: Myofascial pain syndrome is a common multifactorial condition that presents with key manifestations and comorbid with many systemic diseases and regional pain syndromes. Objective: This study aims to concisely review clinical, diagnostic and integrative therapeutic aspects of myofascial pain syndrome. Methods: E-searches (2000-2019) using keywords and Boolean operators were made and using exclusion and inclusion criteria, 50 full articles that focused on myofascial pain syndrome were retained for this review. Results: Myofascial pain syndrome is a multidimensional musculoskeletal disorder with ill-understood etiopathogenesis and pathophysiology and characterized by tender taut muscle with myofascial trigger points, muscle twitch response, specific pattern of referred pain and autonomic symptoms. A variety of pharmacological and nonpharmacological therapies with variable efficacy are used in myofascial pain syndrome, the latter modalities such as education, stretching and exercises, moist hot and cold packs, dry needling and myofascial massage or myofascial trigger point massage are used as first line options. Conclusion: Myofascial pain syndrome and trigger points initiated by repeated strains and injuries co-occur with diverse physical diseases and regional pain syndromes, which need comprehensive diagnostic evaluation using multiple methods. Several interventions are used in patients with myofascial pain syndrome who effectively respond to myofascial massage. This study calls for exploring etiopathogenesis and basic pathophysiological mechanisms underlying myofascial pain syndrome in future.

Epidemiology and socioeconomic impact of the rheumatic diseases on indigenous people: an invisible syndemic public health problem

Epidemiological studies in Latin America suggest indigenous people lack proper healthcare for musculoskeletal (MSK) and rheumatic diseases.ObjectivesThis study aimed to estimate the prevalence of MSK disorders and rheumatic diseases in eight Latin American indigenous communities, and to identify which factors influence such prevalence using network analysis and syndemic approach.MethodsThis is a cross-sectional, community-based census study according to Community-Oriented Program for the Control of Rheumatic Diseases methodology. Individuals with MSK pain, stiffness or swelling in the past and/or during the last 7 days were evaluated by participating physicians. A descriptive, univariable and multivariable analysis was performed, followed by a network analysis.ResultsWe surveyed 6155 indigenous individuals with a mean age of 41.2 years (SD 17.6; range 18–105); 3757 (61.0%) were women. Point prevalence in rank order was: low back pain in 821 (13.3%); osteoarthritis in 598 (9.7%); rheumatic regional pain syndromes in 368 (5.9%); rheumatoid arthritis in 85 (1.3%); undifferentiated arthritis in 13 (0.2%); and spondyloarthritis in 12 (0.1%). There were marked variations in the prevalence of each rheumatic disease among the communities. Multivariate models and network analysis revealed a complex relationship between rheumatic diseases, comorbidities and socioeconomic conditions.ConclusionsThe overall prevalence of MSK disorders in Latin American indigenous communities was 34.5%. Although low back pain and osteoarthritis were the most prevalent rheumatic diseases, wide variations according to population groups occurred. The relationship between rheumatic diseases, comorbidities and socioeconomic conditions allows taking a syndemic approach to the study.