Knowledge graph and emerging trends in β-arrestin research on pain: a bibliometric analysis (1997-2025)

This study aimed to systematically analyze the characteristics of research output, core research foci, and evolutionary trends concerning β-arrestin in the field of pain research from 1997 to 2025 using bibliometric methods. The goal was to clarify the developmental trajectory and identify priority research areas within this domain. This study retrieved literature pertaining to "β-arrestin," "opioid receptors," and "pain" from the Web of Science Core Collection database, Scopus, and PubMed, covering the period from January 1, 1997 to November 22, 2025. Following rigorous screening based on predefined inclusion/exclusion criteria, the eligible publications were systematically analyzed regarding publication trends, core authors and collaborative networks, institutional and national contributions, journal co-citation patterns, co-citation networks of highly influential literature, and keyword clustering with burst detection trends. The final analysis comprised 635 articles. Analysis revealed a steady increase in the number of publications over the period 1997-2025. The USA emerged as the most productive country and also demonstrated the highest scientific influence. The top four institutions by publication volume were University of California System, Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, State University System of Florida, and University of Florida. NATURE was identified as the most frequently cited journal. Keyword analysis indicated that "mu-opioid receptor" exhibited the strongest citation burst strength, while "biased agonism," "opioid receptors," and "G protein" emerged as recent high-frequency terms. The current research hotspots in the field of β-arrestin and pain include directions such as "TRV130 (oliceridine)" and "G protein biased ligand." The research frontier is primarily focused on three key aspects: (1) the pharmacological mechanisms of β-arrestin-mediated pain signaling, (2) the development of G protein-biased ligands, and (3) translational applications for clinical analgesia. Collectively, β-arrestin demonstrates significant potential within the pain research domain. However, core challenges remain: the signaling pathway differences of β-arrestin2 across various pain types are not yet fully elucidated; the "functional selectivity" of biased ligands is difficult to quantify precisely; and the association between the intensity of β-arrestin recruitment and adverse effects remains controversial. Future breakthroughs necessitate interdisciplinary collaboration to fully unlock the therapeutic potential of β-arrestin in pain management.