Hamsa Priya Bhuchakra

Chronic musculoskeletal pain remains a leading cause of disability worldwide, driven by progressive degeneration of cartilage, bone, tendon, intervertebral discs, and peripheral nerves. Conventional interventional approaches primarily address symptoms without restoring structural integrity or tissue homeostasis. Regenerative strategies, including platelet-rich plasma, mesenchymal stem cells, and biomaterials, have demonstrated potential but are limited by variability in outcomes, poor cellular survival, and lack of standardization. Exosomes and extracellular vesicles are key mediators of intercellular communication in tissue repair, reproducing many of the paracrine effects of parent cells while offering improved safety and scalability. These nano-sized vesicles regulate inflammation, angiogenesis, extracellular matrix remodeling, and cell survival across musculoskeletal and neural tissues. Importantly, growing evidence suggests that mechanical cues such as compression, shear stress, and tensile loading not only regulate cellular behavior but also shape exosome biogenesis, cargo composition, and functional effects through mechanotransduction pathways involving integrins, ion channels, and YAP/TAZ signaling. This mechanobiology–exosome interface is particularly relevant in interventional pain medicine, where therapeutics are delivered into mechanically active environments such as joints, discs, tendons, and perineural spaces. Mechanical loading conditions may therefore modulate therapeutic efficacy by shaping both endogenous repair processes and the behavior of administered exosomes. The present investigation reviews the current literature and knowledge on mechanotransduction pathways and exosome biology, with a focus on their intersection in musculoskeletal regeneration. We further examine preclinical and clinical evidence supporting exosome-based therapies in osteoarthritis, degenerative disc disease, tendon and ligament injuries, and neuropathic pain states, alongside key translational challenges including heterogeneity in exosome isolation, dosing, biodistribution, and clinical standardization. Finally, we discuss future directions in mechanobiology-guided exosome engineering and their potential integration into interventional pain practice.

Neurodegenerative diseases are targets for pridopidine therapy, which aims to improve quality of life through neuroprotective mechanisms that involve sigma-1 receptor (S1R) activation. Neurodegenerative motor and cognitive diseases are influenced by dopamine imbalance, where disruptions in pathways contribute to states that are hyperkinetic or hypokinetic, while current dopaminergic treatments are symptomatic rather than disease-modifying, especially for Huntington’s disease and Amyotrophic lateral sclerosis. This review summarizes the mechanisms underlying pridopidine-mediated neuroprotection and examines the current evidence supporting its therapeutic potential. The S1R is an endoplasmic reticulum-mitochondria-associated chaperone involved in homeostasis of calcium, stress regulation, and mitochondrial function. Pridopidine is a small lipophilic molecule that crosses the blood–brain barrier and acts as an S1R agonist, with minimal dopamine D2 receptor occupancy. Activation of S1R by pridopidine modulates calcium signaling and enhances anti-apoptotic activity. Collectively, available evidence suggests that pridopidine may improve motor outcomes and slow disease progression in Huntington’s disease and amyotrophic lateral sclerosis, supporting its promise as a disease-modifying therapeutic strategy.

Persistent postoperative opioid use (PPOU) is an emerging challenge in pediatric perioperative care, with rates as high as 4.7% in opioid-naive adolescents. Despite advances in multimodal analgesia, current protocols often fail to prevent long-term opioid exposure, particularly after high-risk surgeries such as spinal fusions. While multiple strategies exist to reduce PPOU in children, including regional anesthesia and non-opioid analgesics, this review specifically focuses on methadone and pharmacogenomic-guided opioid prescribing as promising approaches. Methadone, a long-acting opioid with mu-opioid agonism, NMDA antagonism, and monoamine reuptake inhibition, has shown encouraging outcomes in adult and emerging pediatric studies but remains underutilized due to concerns over safety, variability, and familiarity. This narrative review explores the intersection of methadone pharmacology, pharmacogenomic (PGx)-guided opioid prescribing, and their potential to reduce PPOU and optimize perioperative pain control in children. We examine methadone’s unique pharmacokinetic profile, extended half-life, and ability to reduce central sensitization and opioid tolerance. Data from pediatric trials in cardiac, spinal, and major abdominal surgeries are reviewed, highlighting methadone’s potential to lower total opioid use, stabilize postoperative pain trajectories, and improve recovery. The review also discusses the role of PGx testing, particularly CYP2D6, CYP3A4, UGT2B7, and OPRM1 variants, in tailoring methadone dosing to individual metabolic profiles, reducing adverse effects, and improving analgesic efficacy. There are no well accepted generalizable perioperative methadone dose, number of doses and dosing intervals due to limited large multicenter studies in children. We outline challenges, including QTc prolongation, dosing variability, lack of pediatric-specific PGx guidelines, and ethical considerations around genetic testing in minors. The review calls for multidisciplinary perioperative teams, expanded PGx implementation, and real-world data from registries and AI-integrated models to support precision opioid strategies. Preventing PPOU in children is critical. Integration of methadone-based multimodal analgesia in high-risk painful in-patient procedures and future integration of PGx represent positive steps toward personalized, effective, and safer pain management in pediatric surgical patients, an urgent need as opioid stewardship becomes a clinical and public health imperative.

Introduction: Headache is a prevalent issue among medical students, stemming from academic pressures, clinical responsibilities, and emotional stressors, with implications for reduced academic performance and co-morbid psychiatric illnesses. Of particular concern is migraine, which may disrupt the acquisition of patient care skills. This study aimed to assess the prevalence of migraine, its associated disability, and contributing factors Methodology: This was a cross sectional assessment of prevalence of migraine, its disability, and contributing factors among 403 MBBS students through a cross-sectional analytical approach. Data encompassed sociodemographic details, perceived academic stress, headache characteristics via the Migraine Screening Questionnaire and Migraine Disability Assessment Questionnaire (MIDAS), and sleep quality evaluated using the Pittsburgh Sleep Quality Index (PSQI), analyzed with SPSS-24. Results: Findings revealed a mean student age of 20.41 years, with females constituting 66%. Migraine prevalence stood at 12.2%, with 24.4% experiencing severe disability. Factors linked to migraine included gender, academic stress, comorbidities, and psychiatric conditions, with the latter emerging as an independent predictor. Notably, lack of sleep emerged as the primary trigger, followed by eye strain or excessive screen time. Conclusion: This study underscores the significance of addressing migraine and poor sleep quality among medical students, highlighting the necessity of promoting good sleep hygiene, effective stress management, and the management of psychiatric comorbidities to bolster student well-being.

Coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has killed millions of people around the world so far and has turned into a disaster for people and healthcare systems. Neurological problems are often seen in people with COVID-19 in the general population, but it is unclear how common they are in pregnant women. This study provides a summary of studies on pregnant women with proven SARS-CoV-2 infection and a particular neurologic diagnosis from different parts of the world. After applying the inclusion and exclusion criteria, a total of 15 papers were assessed to create this review article. Based on our findings, the peripheral and central nervous systems were both equally impacted: Guillain-Barré syndrome (GBS, n=1), bifacial weakness, paresthesia, and vestibulocochlear neuritis (n=1), eclampsia types (n=2), and neurological disease (n=2); case reports, retrospective studies, editorials, and prospective observational studies were included. The median gestational age was 34 (30-36.5) weeks, and the median maternal age was 32.5 (25-35) years. Given the number of reports of neurologic problems associated with COVID-19 in the general community, our findings might be overstated, and we chose the ones that fit our criteria. We hope that this review helps in the early detection and management of neurological diseases during pregnancy.