Involvement of the Transient Receptor Channels in Preclinical Models of Musculoskeletal Pain.

BACKGROUND: Musculoskeletal pain is a condition that affects bones, muscles, and tendons and is present in various diseases and/or clinical conditions. This type of pain represents a growing problem with enormous socioeconomic impacts, highlighting the importance of developing treatments tailored to the patient's needs. TRP is a large family of non-selective cation channels involved in pain perception. Vanilloid (TRPV1 and TRPV4), ankyrin (TRPA1), and melastatin (TRPM8) are involved in physiological functions, including nociception, mediation of neuropeptide release, heat/cold sensing, and mechanical sensation. OBJECTIVE: In this context, we provide an updated view of the most studied preclinical models of muscle hyperalgesia and the role of transient receptor potential (TRP) in these models. METHODS: This review describes preclinical models of muscle hyperalgesia induced by intramuscular administration of algogenic substances and/or induction of muscle damage by physical exercise in the masseter, gastrocnemius, and tibial muscles. RESULTS: The participation of TRPV1, TRPA1, and TRPV4 in different models of musculoskeletal pain was evaluated using pharmacological and genetic tools. All the studies detected the antinociceptive effect of respective antagonists or reduced nociception in knockout mice. CONCLUSION: Hence, TRPV1, TRPV4, and TRPA1 blockers could potentially be utilized in the future for inducing analgesia in muscle hypersensitivity pathologies.

Exposure to Mancozeb results in increased MAPK phosphorylation and locomotor deficits in zebrafish larvae.

Mancozeb is a widely used fungicide whose toxicity has been reported in non-target organisms, being considered to have high or very high acute toxicity to aquatic organisms. However, the toxicity of this compound is not well characterized in the developmental stages of fish. In this study, Danio rerio with 4-, 5-, and 6-days post fertilization (dpf) was exposed to MZ at non-lethal concentrations for 24, 48, or 72 h and subsequently, behavioral alterations, oxidative stress parameters and ERK, p38MAPK, and Akt phosphorylation were analyzed. MZ exposure during the larval period decreased motor performance evaluated by traveled distance, immobile time, and time spent in the peripheral area. In parallel, MZ induced ROS levels and increased the number of cells in apoptosis, causing severe DNA damage, inducing Acetylcholinesterase and Superoxide dismutase activities, and inhibiting Glutathione peroxidase and thioredoxin reductase. Additionally, phosphorylation levels of the proteins p38MAPK, ERK2, and Akt were stimulated. These findings are relevant considering the ecological implications of MZ exposure to fishes in different developmental stages and the role of the MAPK pathway in events like development and cell death.

Interferon-Beta Injection in Multiple Sclerosis Patients Related to the Induction of Headache and Flu-Like Pain Symptoms: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Multiple sclerosis (MS) is a chronic neurodegenerative, inflammatory, and autoimmune disease characterised by the demyelination of the central nervous system. One of the main approaches for treating MS is the use of disease-modifying therapies (DMTs). Among the DMTs are interferons (IFNs), which are cytokines responsible for controlling the activity of the immune system while exerting immunomodulatory, antiviral, and antiproliferative activities. IFN-beta (IFN-ß) is the first-choice drug used to treat relapsing-remitting MS. However, the administration of IFN-ß causes numerous painful adverse effects, resulting in lower adherence to the treatment. Therefore, this study aimed to investigate the headache and flu-like pain symptoms observed after IFNß injection in MS patients using a systematic review and meta-analysis of randomised controlled trials. A total of 2370 articles were identified through research databases. Nine articles were included (three involving IFNß-1b and six involving IFNß-1a). All studies included in the meta-analysis had a low risk of bias. The odds ratio of headache and flu-like pain symptoms increased in MS patients treated with IFN-ß. Thus, the adverse effects of headache and flu-like pain symptoms appear to be linked to IFN-ß treatment in MS. The protocol of the study was registered in the Prospective International Registry of Systematic Reviews (registration number CRD42021227593).