Spinal cord injuries are often devastating and result in severe functional limitations. Our review breaks down the pathophysiology, molecular mechanisms, and omics approaches regarding spinal cord injuries. The pathophysiology can be divided into two main phases, with the secondary phase being of greater interest. Understanding the underlying mechanisms behind these phases allows for targeted approaches to be developed. Advancements in omics technologies (genomics, epigenomics, transcriptomics, proteomics, and metabolomics) are excellent tools in creating tailored spinal cord injury treatment plans. Emerging therapeutic solutions involving ion imbalance, oxidative stress, and mitochondrial dysfunction also show promising results. Mitochondrial transplantation has shown promising initial results in maintaining cellular homeostasis and reducing inflammation. However, significant challenges remain in translating the omics and therapeutic approaches from animal models to clinical trials.

Background/Objectives: Spinal cord injury (SCI) presents significant challenges in restoring motor function, with limited therapeutic options available. Recent advancements in neuromodulation technologies, such as brain-spine interface (BSI), epidural electrical stimulation (EES), and deep brain stimulation (DBS), offer promising solutions. This review article explores the integration of these approaches, focusing on their potential to restore function in SCI patients. Findings: DBS has shown efficacy in SCI treatment with several stimulation sites identified, including the nucleus raphe magnus (NRM) and periaqueductal gray (PAG). However, transitioning from animal to human studies highlights challenges, including the technical risks of targeting the NRM in humans instead of rodent models. Additionally, several other regions have shown potential for motor rehabilitation, including the midbrain locomotor region (MLR) pathways, cuneiform nucleus (CnF), pedunculopontine nucleus (PPN), and lateral hypothalamic. DBS with EES further supports motor recovery in SCI; however, this approach requires high-DBS amplitude, serotonergic pharmacotherapy, and cortical activity decoding to attenuate stress-associated locomotion. BSI combined with EES has recently emerged as a promising novel therapy. Although human studies are limited, animal models have provided evidence supporting its potential. Despite these advancements, the effectiveness of DBS and combined systems remains limited in cases of complete central denervation. Conclusions: The integration and combination of DBS, BSI, and EES represent a transformational approach to treating and restoring function in patients with SCI. While further research is needed to optimize these strategies, these advancements hold immense potential for improving the quality of life in SCI patients and advancing the field of neuromodulation.

Osteoarthritis (OA) is a leading cause of chronic pain worldwide. This is driven by progressive cartilage degradation, inflammation, oxidative stress, and metabolic dysfunction. Current pharmacologic interventions mostly lead to symptomatic relief without actually affecting disease progression. Thus, there is a growing interest in the development of new interventional methods. Our review seeks to synthesize preclinical, translational, and clinical evidence on the impact nutritional methods have on OA management. Whole-diet approaches, such as Mediterranean and plant-based, have been linked to reduced pain, increased physical function, and positive biomarker changes. Bioactive compounds, including curcumin, polyphenols, omega-3 fatty acids, and select herbal extracts, have shown anti-inflammatory, antioxidant, and chondroprotective effects via NF-κB, Nrf2, AMPK, and SIRT1 pathways. This review particularly focuses on plant-derived substances. Emerging nanoparticle technology with regard to advanced delivery systems shows initial promise in nutraceutical pharmacokinetics and tissue targeting. Overall, nutritional interventions are adjunct interventions to OA management. Although these are not full treatment replacements, dietary modifications and targeted nutraceutical strategies with improved delivery systems may lead to more preventive, personalized, and holistic OA management and care.

Background: Chronic pain poses a significant challenge to the general population, especially in older adults. As a result, there is a growing emphasis on developing novel treatment options and expanding the use of emerging technologies. Objective: This comprehensive review aims to guide practitioners in chronic pain management by extending the current application of vagus nerve stimulation (VNS). The review examined peer-reviewed studies, including multicenter cohort studies and clinical trials, published within the past 25 years. VNS has shown the most promising results in pain reduction for headache and migraine, with less relief in inflammatory and neuropathic pain as compared to current first-line treatment options. Conclusion: Overall, this review seeks to compile and critically analyze the effect and efficacy of VNS on different forms of chronic pain using the most current studies and research applicable.