Therapeutic applications of mesenchymal stem cell-derived extracellular vesicles in pain management: A narrative review of emerging evidence and future directions.

Abstract

Pain remains a major clinical challenge because current therapies often have limited efficacy and substantial adverse effects. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are emerging as promising candidates with anti-inflammatory, immunomodulatory, and neuroprotective actions. Preclinical studies show that MSC-EVs alleviate inflammatory, neuropathic, and cancer-related pain by modulating immune responses and promoting neural repair, thereby reducing nociceptor sensitization. MSC-EVs also hold potential as drug-delivery vehicles and as biomarkers for pain diagnosis due to their stability and bioactive cargo (e.g., microRNAs and proteins). This narrative review summarizes terminology, mechanisms, therapeutic applications, and translational challenges of MSC-EVs in pain management, emphasizing their capacity to reshape the treatment landscape. Despite hurdles in scalable manufacturing, dosing, and regulation, ongoing clinical investigations support their promise as a biologically driven strategy for pain therapy.