Search

The C. elegans drug combination assay evaluates the effects of drug combinations in the nematode Caenorhabditis elegans, serving as a valuable tool to assess the efficacy of pharmaceutical agents and natural compounds. Using C. elegans as a model organism, this method allows for the efficient screening of the combined effects of different drugs and evaluation of synergistic effects in drug combinations, which reduces the risk of developing drug resistance. Combination therapy, involving commercial drugs, new agents, or natural products, broadens treatment effectiveness by targeting multiple pathways, effectively managing complex diseases with minimized side effects. The method focuses on discovering effective drug combinations, such as anthelmintic drugs, streamlining early-stage drug discovery to save time and resources. Additionally, its versatility allows for application across most areas of pharmacology and toxicology, extending its usefulness beyond anthelmintic treatments. In the experiments, synchronized worms are exposed to different drug concentrations to evaluate behavioral changes, mostly alterations in worm locomotion. Concentration-response curves for changes in behavior are generated and EC 50 or IC 50 values determined for the individual drugs. To determine whether the effects of a drug combination are synergistic, additive, or antagonistic, at least three different concentration ratios must be tested. These combinations are then analyzed using specialized drug combination analysis software. This methodology ensures consistent and precise outcomes and evaluates drug impacts on worm behavior parameters crucial for effective pharmacological activity. In conclusion, the C. elegans drug combination assay provides critical insights for developing successful market formulations applicable across a wide range of pharmacological treatments. Its ability to efficiently screen for synergistic, additive, or antagonistic effects makes it a valuable tool for identifying effective therapeutic strategies, potentially reducing drug resistance and improving treatment outcomes in various medical and toxicological fields., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2025 Elsevier Inc. All rights reserved.)

The limitations of pharmacological treatments for chronic pain have become increasingly evident: dependency, side effects, resistance, and diminishing efficacy. The urgent need for innovative solutions has become a compelling focus for improving patient outcomes. Innovative non-pharmacological approaches, such as sleep management, as a strategy to reduce opioid consumption and pain control are needed. The aim was to evaluate the impact of a Sleep and Circadian Intervention Program (SCIP) in the control of chronic musculoskeletal pain (CMP). This was a randomized clinical trial (NCT03646084), in which 49 CMP patients were assigned to SCIP ( n = 15, mean age 51 years and 40% women) or non-SCIP groups ( n = 26, 53 years and 61.5% women). Outcomes were evaluated after 6 months through self-reported questionnaires (pain intensity, physical function, depression/anxiety, and quality of life (QoL)). The SCIP group was assessed by polysomnography and specific questionnaires and was treated for diagnosed sleep disorders according to clinical guidelines. This population showed a moderate pain intensity at baseline, important deterioration of QoL and pathological anxiety/fear related to pain. Fifty percent of them presented restless leg syndrome, 60% moderate/severe insomnia, and 62.5% sleep apnea. During the follow-up, the SCIP group presented a greater reduction in the abnormal risk group for anxiety (from 73.3% to 46.7%) and depression (from 53.3% to 33.3%) on the Hospital Anxiety and Depression Scale compared to the non-SCIP group (from 40% to 29.2% and 33.3% to 29.2%, respectively). Also, a positive significant effect on anxiety/fear related to pain was found in the Pain Anxiety Symptoms Scale multivariable model, with an important improvement in symptoms. The application of SCIP in CMP patients improved anxiety and controlled associated sleep disorders, highlighting the impact on insomnia. Larger studies are needed for better understanding of the sleep intervention in CMP control.