Many cases of acute pain can be resolved with few side effects. However, some cases of acute pain may persist beyond the time required for tissue injury recovery and transit to chronic pain, which is hard to treat. The mechanisms underlying pain transition are not entirely understood, and treatment strategies are lacking. In this study, the hyperalgesic priming model was established on rats to study pain transition by injection of carrageenan (Car) and prostaglandin E2 (PGE2). The expression levels of protein kinase C epsilon (PKCε) and transient receptor potential vanilloid 1 (TRPV1) in the L4–L6 dorsal root ganglion (DRG) were investigated. Electroacupuncture (EA) is a form of acupuncture in which a small electric current is passed between a pair of acupuncture needles. EA was administrated, and its effect on hyperalgesia and PKCε and TRPV1 expression was investigated. The PKCε–TRPV1 signaling pathway in DRG was implicated in the pain transition. EA increased the pain threshold of model animals and regulated the high expression of PKCε and TRPV1. Moreover, EA also regulated hyperalgesia and high TRPV1 expression induced by selective PKCε activation. We also found that EA partly increased chronic pain threshold, even though it was only administered between the Car and PGE2 injections. These findings suggested that EA could prevent the transition from acute to chronic pain by inhibiting the PKCε and TRPV1 expression in the peripheral nervous system.

Background: The prevalence of pain comorbid and anxiety/depression in clinical observations has been high, and the number of related publications has increased in recent years. Nevertheless, few studies have used bibliometric methods to analyze the scientific research on comorbid pain and depression/anxiety. The aim of this study was to systematically examine the trends in global scientific research on comorbid pain and depression/anxiety from 2012 to 2022. Methods: Papers published between 2012 and 2022 were identified in the Web of Science database. Publications that examined comorbid pain and depression/anxiety were included. The language was limited to English. CiteSpace, Excel and VOSviewer were used to analyze the volume of publications, countries, institutions, authors, cocited authors, and keywords. Results: A total of 30,290 papers met the inclusion criteria of the study. Using CiteSpace, VOSviewer and Excel, the results showed that the United States (10,614 publications), Harvard University (1195 publications), and Jensen, Mark P. (77 publications) were the most productive country, institution, and author, respectively. The hotspots and frontiers were “relationship between depression and pain”, “gender differences in pain and depression/anxiety domains”, “study of specific pain types with depression/anxiety”, “treatment of pain combined with anxiety/depression”, and “effects of COVID-19 on patients with pain combined with depression/anxiety”. Conclusion: These findings indicate a growing interest in the field of comorbid pain and depression/anxiety. The research has been broad and deep, but there is still much room for growth. Furthermore, there is a need for more mature global collaborative networks as well as more high-quality research results in the future.

Pain-related aversive memory is common in chronic pain patients. Electroacupuncture has been demonstrated to block pain-related aversive memory. The insular cortex is a key region closely related to aversive behaviors. In our study, a potential mechanism underlying the effect of electroacupuncture treatment on pain-related aversive memory behaviors relative to the insular cortex was investigated. Our study used the chemogenetic method, pharmacological method, electroacupuncture intervention, and behavioral detection. Our study showed that both inhibition of gamma-aminobutyric acidergic neurons and activation of the kappa opioid receptor in the insular cortex blocked the pain-related aversive memory behaviors induced by 2 crossover injections of carrageenan in mice; conversely, both the activation of gamma-aminobutyric acidergic neurons and inhibition of kappa opioid receptor in the insular cortex play similar roles in inducing pain-related aversive memory behaviors following 2 crossover injections of carrageenan. In addition, activation of gamma-aminobutyric acidergic neurons in the insular cortex reversed the effect of kappa opioid receptor activation in the insular cortex. Moreover, electroacupuncture effectively blocked pain-related aversive memory behaviors in model mice, which was reversed by both activation of gamma-aminobutyric acidergic neurons and inhibition of kappa opioid receptor in the insular cortex. The effect of electroacupuncture on blocking pain-related aversive memory behaviors may be related to the activation of the kappa opioid receptor and inhibition of gamma-aminobutyric acidergic neurons in the insular cortex.

Aims: This study aimed to address the lack of comprehensive reviews on the comorbidity between depression and type 2 diabetes mellitus (T2DM) by investigating their complex connections and identifying emerging research trends. Methods: We conducted an in-depth review combining macro bibliometric analysis and micro content interpretation of literature. Based on the bibliometric analysis of 3,986 papers in Web of Science Core Collection and 238 clinical trials in PubMed published between 2016 and 2025, the institutions, countries, authors and keywords were investigated, and the research maps were drawn by bibliometric software such as VOSviewer, Citespace and Bibliometrix. Meanwhile, micro interpretation entails in-depth content analysis of key articles to develop personal insights. Results: The analysis identified 3,986 relevant papers and 238 clinical trials, revealing a consistent overall growth in research volume. Key contributing entities and potential future research hotspots are mapped, such as the link between comorbidity and Parkinson’s disease and obesity. Also, our micro-interpretation identified the comorbidity mechanism through hypothalamic pituitary adrenal axis (HPA axis) and Brain derived neurotrophic factor (BDNF) and integrated treatment strategy of depression and T2DM. Conclusion: The results of the study outlined the evolving knowledge and research focus in this field. This study provides a comprehensive review of the comorbidity of depression and T2DM, emphasizing the mechanism and treatment of the comorbidity. The current research focus is on the HPA axis and BDNF, and the integrated treatment idea to solve depression and T2DM at the same time has the potential to change in chronic disease management and clinical practice.

Background: Pruritus is a common skin symptom, frequently associated with substantial psychological burden. Recent advances in neuroscience and clinical practice suggest a clinically significant reciprocal association between chronic pruritus and negative emotions (e.g., anxiety and depression), moving beyond simple models of causality. Despite increasing research interest, this interdisciplinary field still lacks a comprehensive bibliometric overview. Therefore, this study aims to systematically visualize the research landscape and identify emerging hotspots, underexplored areas, and translational priorities regarding the pruritus-emotion interplay. Methods: Literature data were retrieved from the Web of Science Core Collection (WoSCC) and supplemented with targeted PubMed clinical trials published from January 1, 1980, to May 31, 2026. WoSCC records served as the main bibliometric dataset, whereas PubMed clinical trials were screened according to predefined eligibility criteria and used as a supplementary clinical-trial dataset. The final included records and records excluded after full-text assessment were verified by a second reviewer. Advanced bibliometric tools, including VOSviewer, CiteSpace, Charticulator and Bibliometrix were used to evaluate collaboration networks, co-citation relationships, and keyword evolution. Results: A total of 2549 publications from WoSCC and 46 clinical trials from PubMed were included. The United States exhibited absolute advantages in publication volume, citation influence, and international cooperation. The leading institutions were mainly located in North America and Europe, including the University of Toronto, University of Miami, and Wroclaw Medical University. Szepietowski J.C., Yosipovitch G., and Ständer S. were the most productive authors, while Yosipovitch G. and Silverberg J.I. occupied central positions in the co-citation network. The supplementary PubMed clinical trial analysis indicated that targeted pharmacological therapies were more frequently represented than psychological, behavioral, or integrative interventions. The integrated findings identified five interrelated themes: anxiety and depression as the principal emotional constructs, the crucial implementation of multidimensional patient-reported outcome measures (PROMs), sleep and cognitive amplifiers, targeted and integrative care, and skin-brain axis mechanisms. Conclusion: This bibliometric analysis provides a structured overview of the research landscape on pruritus and negative emotions. By revealing emerging trends and future research priorities, this study serves as a valuable reference for scholars and clinicians exploring interdisciplinary interventions to break this vicious cycle.