Traumatic brain injury is one of the leading causes of morbidity and mortality worldwide and is one of the major public healthcare burdens in the US, with millions of patients suffering from the traumatic brain injury itself (approximately 1.6 million/year) or its repercussions (2–6 million patients with disabilities). The severity of traumatic brain injury can range from mild transient neurological dysfunction or impairment to severe profound disability that leaves patients completely non-functional. Indications for treatment differ based on the injury’s severity, but one of the goals of early treatment is to prevent secondary brain injury. Hemodynamic stability, monitoring and treatment of intracranial pressure, maintenance of cerebral perfusion pressure, support of adequate oxygenation and ventilation, administration of hyperosmolar agents and/or sedatives, nutritional support, and seizure prophylaxis are the mainstays of medical treatment for severe traumatic brain injury. Surgical management options include decompressive craniectomy or cerebrospinal fluid drainage via the insertion of an external ventricular drain. Several emerging treatment modalities are being investigated, such as anti-excitotoxic agents, anti-ischemic and cerebral dysregulation agents, S100B protein, erythropoietin, endogenous neuroprotectors, anti-inflammatory agents, and stem cell and neuronal restoration agents, among others.

Background: Chronic pain remains a major clinical challenge, which is often resistant to conventional treatments. Spinal cord stimulation has been used for decades to manage refractory pain, traditionally relying on open-loop systems with fixed-output stimulation. However, these systems fail to account for physiological variability, leading to inconsistent pain relief. Closed-loop spinal cord stimulation represents a significant advancement by utilizing evoked compound action potentials to continuously modulate stimulation intensity in real-time, ensuring more stable and effective pain management. Methods: A comprehensive literature review was conducted using PubMed and ClinicalTrials.gov to identify and synthesize relevant published and ongoing studies with a focus on open-loop spinal cord stimulation for managing lower back pain. Results: Clinical trials, including the Avalon and Evoke studies, have demonstrated that closed-loop spinal cord stimulation provides superior pain relief, functional improvement, and reduced opioid dependence compared to traditional open-loop systems. Patients receiving closed-loop stimulation reported significantly higher rates of sustained pain reduction, improved quality of life, and fewer complications related to overstimulation. Emerging studies suggest its potential for conditions beyond back pain, such as neuropathic pain, cancer-related pain, and Raynaud’s phenomenon. Furthermore, cost-effectiveness analyses indicate that closed-loop spinal cord stimulation is a more economically viable treatment option compared to conventional medical management and open-loop systems. Conclusions: Closed-loop spinal cord stimulation represents a transformative development in neuromodulation, offering personalized and adaptive pain management that is distinct from open-loop spinal cord stimulation. Further research is warranted to explore its long-term durability, broader applications, and integration with emerging technologies in pain management.

Background: Chronic low back pain (CLBP) is the leading cause of disability both within the United States and globally. However, reliable diagnosis and treatment remains limited due to a lack of objective and image-based biomarkers. Modic changes (MCs) are visible vertebral endplate and bone marrow changes in signal intensity seen on MRI. MCs have emerged as promising correlates with degenerative disc disease and CLBP. Methods: This is a non-systematic literature review. Results: This review synthesizes current evidence on the classification, pathophysiology, and imaging of MCs, with a particular focus on their associations with patient-reported outcomes, including pain (Visual Analog Scale), functional status (Oswestry disability index and Roland-Morris Disability Questionnaire), and health-related quality of life (Short Form-36 and EuroQol 5-Dimension 5 Level). MC type 1 and 2 show significant correlations with symptom severity and predict positive response to basi-vertebral nerve (BVN) ablation, a minimally invasive intervention inhibiting the nerves’ ability to transmit pain signals. Conclusions: Across multiple trials, BVN ablation has shown significant sustained improvements in patient-reported outcomes among patients with MC, reinforcing their role as both a diagnostic and therapeutic biomarker.

Chronic pain is a debilitating condition that affects millions of patients worldwide, contributing to a high disease burden and millions of dollars in lost wages, missed workdays, and healthcare costs. Opioids, NSAIDs, acetaminophen, gabapentinoids, muscle relaxants, anticonvulsants, and antidepressants are the most used medications for chronic pain and carry significant side effects, including gastric bleeding, hepatotoxicity, stroke, kidney damage, constipation, dizziness, and arrhythmias. Opioids in particular carry the risk of long-term dependence, drug tolerance, and overdose. In 2022, 81,806 people died from opioid overdose in the United States alone. Alternative treatments for chronic pain are critically needed, and nanotechnology has emerged as a promising means of achieving effective long-term analgesia while avoiding the adverse side effects associated with conventional pharmacological agents. Nanotechnology-based treatments include liposomes, Poly Lactic-co-Glycolic Acid (PLGA) and other polymeric nanoparticles, and carbon-based polymers, which can help mitigate those adverse side effects. These nanomaterials can serve as drug delivery systems that facilitate controlled release and drug stability via the encapsulation of free molecules and protein-based drugs, leading to longer-lasting analgesia and minimizing side effects. In this review, we examine the role of nanotechnology in addressing concerns associated with conventional chronic pain treatments and discuss the ongoing efforts to develop novel, nanotechnology-based treatments for chronic pain such as nanocapacitor patches, gene therapy, the use of both viral and non-viral vectors, CRISPR, and scavengers.