A Multi-Database Bibliometric and Translational Mapping of Microglial Mechanisms in Spinal Cord Pain Signaling.

内容摘要

This multi-source bibliometric and translational mapping study provides a panoramic synthesis of how research on microglia-mediated spinal pain signaling has evolved from foundational mechanistic studies to clinically oriented innovations. The aim is to identify developmental trajectories, mechanistic hotspots, and translational opportunities, thereby offering strategic insight into guiding the future direction of neuropathic pain research. We analyzed 1313 original research papers from the Web of Science Core Collection (WoSCC; 2005-2024) using CiteSpace and VOSviewer to construct collaboration networks, journal co-citation graphs, and keyword-driven mechanism clustering. To add a translational medicine dimension, we conducted a targeted PubMed search ("microglia AND spinal cord AND (translational OR therapeutic OR drug targets)"), retrieving 692 additional records, enabling cross-database overlay to link mechanistic themes with specific therapeutic targets. The scientometric model indicates that spinal pain research has shifted from primarily descriptive work to more detailed regulatory models. Key themes include glial cell activation, oxidative stress, mitochondrial dysfunction, and changes in microglia state. Research on heat shock protein pathways and sex-related microglial responses is also increasing. Some core terms have remained frequent over the years, such as "neuroinflammation" and "activated protein kinases". In contrast, the explosive emergence of brain-derived neurotrophic factor (BDNF) and spinal cord stimulation (2020-2021; burst intensity = 2.56) indicates a growing interest in synaptic and circuit control and neuromodulation-based approaches. In the PubMed subset, 33.6% of studies directly focused on treatment development, with gene therapy, intrathecal administration, and microenvironment remediation also appearing more frequently. When we combine data from WoSCC and PubMed over the past 20 years, we can see a significant shift in the explanation of spinal pain in this field. Early research often described the problem as "glial cell activation-cytokine release." Recent research, however, focuses on specific pathways, particularly microglial state regulation, oxidative stress-autophagy connections, and kinase signaling. This shift in treatment approaches is also reflected in translational studies. Many studies no longer rely primarily on systemic drugs but instead focus on targeted strategies such as intrathecal administration, gene or cell therapy, extracellular vesicles, and neuromodulation. These trends make polarization-related molecular nodes ideal candidate targets for precision analgesia. However, bibliometric results are dependent on database coverage, keyword processing, and clustering settings. Some "hotspots" may reflect changes in terminology or citation habits rather than true mechanistic importance. The rise of neuromodulation keywords may also reflect broader clinical applications; microglial mechanisms are plausible, but contributions from other circuit-level mechanisms may also play a role. These results indicate that the field is moving beyond a purely inflammatory perspective toward systemic intervention models. Currently, there is a greater focus on microglial homeostasis and M2-like anti-inflammatory/immune repair processes, as well as sex and metabolic factors that may influence responses. This research direction supports immune repair and more personalized analgesia. Simultaneously, stronger mechanistic arguments require cell state-specific measurements rather than broad phenotypic labels.