Preclinical models of stem cell-mediated analgesia and tissue repair: mechanisms, challenges, and future directions.

As an emerging biological therapeutic approach, stem cell therapy demonstrates broad application prospects in analgesia and tissue regeneration, particularly achieving significant advances in treating conditions such as spinal cord injury and intervertebral disc degeneration. In recent years, preclinical model studies have deepened our understanding of the mechanisms underlying stem cell-mediated pain relief and tissue repair, revealing their potential to regulate inflammatory responses, promote nerve regeneration, and repair damaged tissues through multiple pathways. However, the heterogeneity of preclinical models and the discrepancies between these models and clinical practice, coupled with often insufficient critical appraisal of study quality, remain critical issues requiring urgent resolution in this field. This narrative review systematically summarizes the fundamental theories and key mechanisms underlying stem cell-mediated analgesia and regeneration. It comprehensively evaluates the advantages and limitations of different animal models, critically analyzes major controversies and technical challenges in research, and identifies key directions for future studies. The literature discussed herein was identified through searches in PubMed and Web of Science databases, focusing on recent preclinical studies (primarily within the last decade) involving stem cells, pain models, and tissue regeneration. Selected studies were evaluated for their methodological rigor and contribution to mechanistic understanding. This review aims to synthesize current evidence, critically appraise preclinical models, and provide a forward-looking perspective for research on stem cell-related analgesia and regenerative mechanisms, thereby promoting further development in clinical translation.