Intervertebral disc degeneration (IDD) is a major contributor to back, neck, and radicular pain. It is related to changes in tissue structure and function, including the breakdown of the extracellular matrix (ECM), aging, apoptosis of the nucleus pulposus, and biomechanical tissue impairment. Recently, an increasing number of studies have demonstrated that inflammatory mediators play a crucial role in IDD, and they are being explored as potential treatment targets for IDD and associated disorders. For example, interleukins (IL), tumour necrosis factor-α (TNF-α), chemokines, and inflammasomes have all been linked to the pathophysiology of IDD. These inflammatory mediators are found in high concentrations in intervertebral disc (IVD) tissues and cells and are associated with the severity of LBP and IDD. It is feasible to reduce the production of these proinflammatory mediators and develop a novel therapy for IDD, which will be a hotspot of future research. In this review, the effects of inflammatory mediators in IDD were described.

Objective. Although low-dose ketamine has been shown to be generally beneficial in terms of pain control in a variety of major surgery, there is no consensus regarding the effectiveness of supplemental ketamine analgesic use exclusively in spine surgery. The objective of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to assess the efficacy and safety of perioperative low-dose ketamine for pain management and analgesic consumption in patients undergoing spine surgery. Methods. A comprehensive literature search was performed for relevant studies using PubMed, EMBASE, Web of Science, and Cochrane Library. Patients who received perioperative low-dose ketamine were compared to the control group in terms of postoperative pain intensity, opioid consumption, and adverse events. Patients were further categorized by ages and administration times for subgroup analysis. Results. A total of 30 RCTs comprising 1,865 patients undergoing elective spine surgery were included. Significantly lower pain intensity and less opioid consumption at 12 h, 24 h, and 48 h postoperatively and lower incidence of postoperative nausea and vomiting (PONV) were observed in the ketamine group (all ). There was no significant difference of central nervous system (CNS) adverse events between groups. However, different efficacy of low-dose ketamine was detected when patients were categorized by ages and administration times. Conclusion. Perioperative low-dose ketamine demonstrated analgesic and morphine-sparing effect with no increased adverse events after spine surgery. However, this effect was not significant in pediatric patients. Only postoperative or intraoperative and postoperative administration could prolong the analgesic time up to 48 h postoperatively. Further studies should focus on the optimal protocol of ketamine administration and its effect on old age participants.

Background. Pain following orthopedic surgery has always been a critical issue, which caused great distress to the patients. Analgesics in the treatment of postoperative pain following orthopedic surgery have aroused great attention from scholars, and numerous studies have been published in recent years. Bibliometrics could assist scholars in understanding the scope of research topics better, identifying research focuses and key literature, and analyzing the development and trend of analgesics in the treatment of postoperative pain following orthopedic surgery. Methods. Literature data were retrieved from the Science Citation Index Expanded (SCI-E) of Web of Science (WOS) Core collection database. The articles from 1992 to December 2021 on analgesics in the treatment of postoperative pain following orthopedic surgery were recruited. The citation reports including the publication numbers, h-index, total citations, and average citations in terms of authors, organizations, and countries were obtained. Top 20 research directions, funds, and journals with the most publications were charted. The co-authorship relations in the analysis units of authors, organizations, and countries were analyzed by the online bibliometric tool and VOSviewer software. The authors keywords co-occurrence overlay map was visualized by the VOSviewer software. Results. A total of 406 articles were retrieved from 1992 to December 4th, 2021, with 11,655 times cited, average citations of 28.57 per item, and an h-index of 55. The most high-yield publication year, authors, organizations, countries, research directions, funds, and journals were 2020 (n=887), Ilfeld BM from University of California San Diego (n=7), University of California System (n=21), the USA (n=178), Anesthesiology (n=161), National Institutes of Health (NIH), USA, and United States Department of Health Human Services (n=12), and Anesthesia and Analgesia (n=29), respectively. Similarly, co-authoring analysis of publications regarding on different analgesics showed that the authors and countries with the most co-authorship strength were Carr Daniel B (total link strength=6) and the USA (total link strength=30), respectively. The highest occurrence keywords were postoperative pain with 135 occurrences (total link strength=784). The future research hotspots might be acute pain, outcomes, oxycodone, total hip, replacement, and United States. Conclusion. Analgesics in the treatment of postoperative pain following orthopedic surgery can be observed in this study by employing the online bibliometric tool and VOSviewer software, which established the relationship between the units of analysis. It can provide a meaningful resource with detailed information for orthopedic surgeons who would like to understand the trend in this field better. They can also benefit from the emphasis on citation count to carry out high-level research in the future.

Background. Stem cell therapy is a promising therapeutic modality for intervertebral disc degeneration (IDD). Oxidative stress is a vital contributor to the IDD; however, the definite role of oxidative stress in stem cell therapy for IDD remains obscure. The aim of this study was to determine the vital role of oxidative stress-related differentially expressed genes (OSRDEGs) in degenerative NPCs cocultured with mesenchymal stem cells (MSCs). Methods. A series of bioinformatic methods were used to calculate the oxidative stress score and autophagy score, identify the OSRDEGs, conduct the function enrichment analysis and protein-protein interaction (PPI) analysis, build the relevant competing endogenous RNA (ceRNA) regulatory networks, and explore the potential association between oxidative stress and autophagy in degenerative NPCs cocultured with MSCs. Results. There was a significantly different oxidative stress score between NPC/MSC samples and NPC samples ( ). Forty-one OSRDEGs were selected for the function enrichment and PPI analyses. Ten hub OSRDEGs were obtained according to the PPI score, including JUN, CAT, PTGS2, TLR4, FOS, APOE, EDN1, TXNRD1, LRRK2, and KLF2. The ceRNA regulatory network, which contained 17 DElncRNAs, 240 miRNAs, and 10 hub OSRDEGs, was constructed. Moreover, a significant relationship between the oxidative stress score and autophagy score was observed ( ), and 125 significantly related gene pairs were obtained ( , ). Conclusion. Stem cell therapy might repair the degenerative IVD via reducing the oxidative stress through the ceRNA regulatory work and restoration of autophagy in degenerative NPCs. This research could provide new insights into the mechanism research of stem cell therapy for IDD and potential therapeutic targets in the IDD treatment.

Low back pain (LBP) is a common clinical symptom, and the prevalence is ranged from 60% to 70%. With the deepening of basic research, the development of intervertebral disc regeneration-oriented cell therapy, especially stem and progenitor cells therapy, showed good research prospects and was expected to become new methods of treatment for LBP. Our study is aimed at analyzing the scientific output of stem and progenitor cells in intervertebral discs and at driving future research into new publications. Researches focused on this file were searched from the Science Citation Index Expanded (SCI-E) of the Web of Science (WOS) core collection database and were screened according to inclusion criteria. We evaluated and visualized the results, including annual publications, citations, authors, organizations, countries, research directions, funds, and journals by bibliometric website, VOSviewer, and Citespace softwares on May 27, 2022. A total of 450 original articles and reviews were included, and the overall trend of the number of publications rapidly increased. In worldwide, China and the USA were the leading countries for research production. The retrieved 450 publications received 14322 citations, with an average of 31.83 citations and an H-index of 62. The most high-yield author, organization, country, research directions, funds, and journals were Chen QX from Zhejiang University, Zhejiang University, China, Cell Biology, National Natural Science Foundation of China, and Spine, respectively. Keywords cluster analysis showed the research hotspots in the future, including “human intervertebral disc”, “adipose-derived mesenchymal stem cell”, “intervertebral disc degeneration”, “degenerative disc model”, “nucleus pulposus regeneration”, “human cartilage”, “3d culture”, “shrinkage-free preparation”, and “polylactide disc”. Furthermore, with accumulating evidence demonstrating the role of stem and progenitor cells in intervertebral discs, “microenvironment”, “activation”, “intervertebral disc degeneration”, and “oxidative stress” are becoming the research frontiers and trends.

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