BACKGROUND:Pain following traumatic brain injury (TBI) is a major challenge in clinical management. Neuroinflammatory responses, particularly those involving microglia, are increasingly implicated in the synaptic and circuit-level remodeling associated with post-TBI pain. However, the conventional M1/M2 framework does not adequately capture the temporal and functional diversity of microglial states after injury. This study aimed to characterize microglial heterogeneity and identify specific microglial subpopulations potentially associated with post-TBI pain-related neural remodeling. METHODS:We reanalyzed the publicly available single-cell RNA sequencing dataset GSE226207, which comprised intact cortical samples and cortical samples collected at 3 and 5 days after cortical stab-wound injury from control and inhibitor-treated mice. The inhibitor-treated groups received combined pharmacological inhibition of the CXCR3 and TLR1/2 pathways. Seurat was used for data processing, clustering, cell-type annotation, and microglial subclustering. AUCell was applied to evaluate inflammatory-, repair-, and pain-relevant gene signatures. CytoTRACE and Slingshot were used to assess relative transcriptional complexity and infer state-transition trajectories. CellChat analysis of pooled cells from all groups was performed to predict intercellular communication, and SCENIC was used to characterize subpopulation-associated regulon activity. RESULTS:A total of 66,310 cells were retained, including 7648 microglia that were resolved into eight transcriptionally distinct subpopulations. Among them, the Lars2+ microglial subpopulation showed lower representation in the 3 days postinjury (dpi) groups and greater representation in the 5 dpi groups. This subpopulation exhibited relatively high TGF-β- and MAPK-associated signature scores and was enriched in biological processes related to synaptic organization, axonogenesis, dendrite development, and protein synthesis. Slingshot positioned Lars2+ microglia at the distal end of one inferred state-transition lineage. CellChat analysis predicted prominent neuron-to-microglia communication through the CX3CL1-CX3CR1 ligand-receptor pair, with Lars2+ microglia predominantly positioned as signal receivers. SCENIC further identified relatively high activity of regulatory module M1 in Lars2+ microglia, with Thra among the highly ranked regulators. CONCLUSION:This study identifies the Lars2+ microglial subpopulation as a temporally dynamic and transcriptionally specialized component of the postinjury microglial landscape. The convergence of pain-relevant signaling signatures, neural remodeling programs, inferred state-transition characteristics, predicted neuron-microglia communication involving the CX3CL1-CX3CR1 pair, and Thra-associated regulon activity supports a potential role for Lars2+ microglia in posttraumatic neuroimmune and synaptic remodeling. These findings provide a cellular and molecular framework for future investigation of microglia-targeted strategies for post-TBI pain.
STUDY DESIGN:Bibliometric analysis. OBJECTIVE:To optimize pain management and identify future research trends through bibliometric analysis. SUMMARY OF BACKGROUND DATA:Postoperative lumbar spine pain is multifactorial and often persists despite successful surgery, reducing patients' quality of life, increasing healthcare use, and increasing the risks of opioid dependence and psychological distress. METHODS:Data from eligible studies were extracted through a comprehensive search and various analyses, including descriptive bibliometrics, citations, keywords, and thematic analyses. Group comparisons were made between Asian and non-Asian groups to assess differences and trends between the two regions. RESULTS:Between 1984 and 2025, 197 studies were published, with an average annual increase of 1.70%. At least 10 studies were contributed by the USA, Turkey, Iran, China, and Korea. Studies from the USA had the highest annual citations, whereas those from Spain had the highest citations per article. The focus of most studies (96.45%) was on pharmacological interventions, including anesthetics, opioids, nonsteroidal anti-inflammatory drugs, antipyretic-analgesic drugs, corticosteroids, serotonin-norepinephrine reuptake inhibitors, nonopioid centrally acting analgesics, and nondepolarizing neuromuscular blockers. Among these, intravenous administration was used in 48.22% of the studies, and 58.38% employed a placebo as the control. Additionally, 77.16% of the studies used the Visual Analog Scale to assess pain. Overall, the field has shifted from basic pain management to more personalized and multifaceted perioperative strategies, especially for patients undergoing complex spinal surgeries. Significant differences were observed between the Asian and non-Asian groups regarding publication year and age. CONCLUSIONS:The number of randomized controlled trials on lumbar postoperative pain has increased, with the USA, Turkey, Iran, and Korea dominating the research. China's lower citation ranking was lower on citation-based indicators; limited international visibility is proposed as a hypothesis for this pattern rather than an established explanation. Driven by the opioid crisis, the field has evolved from opioid-sparing strategies to multimodal, personalized care.
BACKGROUND:Cancer pain (CP) is predominantly caused by bone metastases, imposing a significant burden on both patients and society. The limitations of the three-step analgesic (TSA) therapy in managing CP have become increasingly evident. Although acupuncture demonstrates promising therapeutic effects for this condition, there is currently limited research comparing the efficacy of different acupuncture modalities. RESULTS:A total of 20 studies were included, involving 1640 patients. The tumor types included lung cancer, prostate cancer, colorectal cancer, bile duct cancer, and breast cancer. A total of 9 acupuncture therapies were involved: acupoint embedding, auricular point pressing, electroacupuncture, ordinary acupuncture, bee therapy, fire needle therapy, moxibustion, acupoint injection, and acupoint application. The main outcome indicators were pain relief rate and NRS score, while the secondary outcome was the incidence of adverse reactions. The consistency test results showed no significant inconsistency among the comparison groups (p > 0.05), and a consistency model analysis was adopted. In terms of pain relief rate, electroacupuncture combined with auricular point pressing combined with the TSA therapy ranked the top three (SUCRA = 0.90), moxibustion combined with the TSA therapy ranked the top three (SUCRA = 0.84), and auricular point pressing combined with the TSA therapy ranked the top three (SUCRA = 0.65). In terms of reducing NRS scores, auricular point pressing combined with the TSA therapy ranked the top (SUCRA = 0.95), bee therapy combined with the TSA therapy ranked the top (SUCRA = 0.83), and acupuncture combined with acupoint injection combined with the TSA therapy ranked the top (SUCRA = 0.70). In terms of safety, the adverse reaction rate of fire needle therapy combined with the TSA therapy was the lowest (SUCRA = 0.98), electroacupuncture combined with auricular point pressing combined with the TSA therapy ranked the top (SUCRA = 0.81), and acupoint embedding combined with the TSA therapy ranked the top (SUCRA = 0.67). In terms of overall efficacy and safety, auricular point pressing combined with the TSA therapy performed the best in the benefit-risk assessment. CONCLUSION:Acupuncture combined with the TSA therapy can effectively relieve CP in bone metastasis, with fewer adverse reactions. The current evidence indicates that auricular point pressing combined with the TSA therapy is the best treatment option in terms of comprehensive benefits. Due to the limited number of included studies, low quality of evidence, and potential bias risks, the conclusion still needs to be further verified by high-quality research.
BACKGROUND:Intravenous ketamine and lidocaine infusions are increasingly used for chronic peripheral neuropathic pain, particularly in refractory cases. However, comparative data on their short- and midterm analgesic outcomes in routine clinical practice are limited. METHODS:This retrospective study included patients with chronic peripheral neuropathic pain who received intravenous ketamine or lidocaine infusion between January and May 2021. Ketamine was administered at 1 mg/kg/h and lidocaine at 3 mg/kg/h for five consecutive days. Pain intensity and neuropathic pain features were assessed using the Numeric Rating Scale (NRS) and the Douleur Neuropathique 4 (DN4) questionnaire at baseline and at 2 weeks, 2 months, and 6 months after treatment. Clinically meaningful pain relief was defined as a ≥ 50% reduction in pain scores. RESULTS:A total of 102 patients were analyzed (ketamine group, n = 44; lidocaine group, n = 58). Both groups showed significant reductions in NRS and DN4 scores at all follow-up points compared with baseline (p < 0.01). Clinically meaningful pain relief was more frequent in the ketamine group at 2 weeks (p < 0.01), whereas no significant differences were observed at 2 and 6 months (p > 0.05). Adverse effects occurred more often with ketamine, while lidocaine was associated with fewer side effects (p < 0.05). CONCLUSION:Ketamine provided a greater early analgesic response at 2 weeks, whereas both treatments demonstrated comparable midterm efficacy at 2 and 6 months. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT06297915.
OBJECTIVE:Neuropathic pain typically develops after nerve injury and is largely driven by microglial activation in the central nervous system (CNS), with colony-stimulating factor 1 (CSF1) serving as a key initiator. We analyzed mRNA and microRNA expression profiles in CSF1-stimulated primary microglia using next-generation sequencing, followed by integrative bioinformatic analyses. METHODS:Rat microglia were cultured in microglial medium at 37°C with 5% CO2 and treated with CSF1 (20 ng/mL) for 16 h to assess early transcriptional and miRNA-mRNA responses. Total RNA was extracted using TRIzol and quantified using a Nanodrop and Bioanalyzer. RNA libraries were prepared with the SureSelect kit and sequenced on an Illumina platform. Differentially expressed mRNAs were defined as those with a fold change ≥ 2 and an FDR-adjusted p value < 0.05, whereas differentially expressed miRNAs were identified using a fold change ≥ 1.5 for both upregulated and downregulated miRNAs with a p value < 0.05. The miRNA-mRNA interactions were assessed using miRWalk, and KEGG/GO analyses identified pathways related to inflammation, immune signaling, and extracellular matrix (ECM) remodeling. RESULTS:CSF1 stimulation altered the expression of 176 miRNAs and 429 mRNAs, including 86 upregulated and 90 downregulated miRNAs. Inverse correlation analysis revealed 68 downregulated miRNAs linked to 119 upregulated mRNAs, and 69 upregulated miRNAs linked to 204 downregulated mRNAs, indicating complex regulatory interactions. The transcriptional program induced by CSF1 was characterized by increased expression of proinflammatory and proliferative genes, such as Fos, Cxcl2, and Ephb3, and suppressed expression of ECM- and glycosaminoglycan (GAG)-related genes, including Gpc6 and Prelp. Several miRNAs, including rno-miR-652-5p, rno-miR-672-5p, rno-miR-455-3p, rno-miR-145-5p, rno-miR-222-3p, rno-miR-702-5p, rno-miR-877, rno-miR-664-2-5p, and rno-miR-702-3p, emerged as potential upstream regulators of these changes. Pathway enrichment analysis highlighted the activation of TNF, IL-17, and mitogen-activated protein kinase (MAPK) signaling, coupled with the suppression of ECM remodeling. CONCLUSION:These findings identify candidate miRNA-mRNA regulatory networks associated with CSF1-driven microglial responses and provide new insights into transcriptomic changes relevant to neuroimmune mechanisms in neuropathic pain.
OBJECTIVES:Treatments for neuropathic cancer pain (NCP) are often based on guidelines or treatment data for neuropathic pain of noncancer origin. Therefore, their relative efficacy and safety are not well characterized and should be determined. This study aimed to compare the efficacy and safety of various pharmacological interventions for NCP. METHODS:We systematically searched PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for relevant randomized controlled trials (RCTs) from inception to June 13, 2024; 36 studies were included. The primary outcome was pain intensity; secondary outcomes included the effective pain relief rate, nausea and vomiting, and overall adverse events. The certainty of evidence was assessed using the CINeMA web application. RESULTS:The combination of opioids, antiepileptics, and nonsteroidal anti-inflammatory drugs (NSAIDs) appeared to be the most effective treatment to reduce pain intensity (surface under the cumulative ranking [SUCRA] curve: 0.91), followed by the combination of antiepileptics and antidepressants (SUCRA: 0.90). For secondary outcomes, the combination of opioids and neurotropin was associated with the highest probability of achieving the best pain relief rate (SUCRA: 0.81), whereas vitamin B12 appeared to be relatively ineffective. Regarding safety, vitamin B12 was associated with the highest probability of being the safest treatment for nausea and vomiting (SUCRA: 0.90), followed by antiepileptic drugs (SUCRA: 0.87). For overall adverse events, antidepressants were associated with the highest probability of being the safest treatment (SUCRA: 0.86). For the primary outcome, 84.8% of the comparisons were rated as being of low or very low confidence according to the CINeMA method. CONCLUSIONS:Antiepileptics and antidepressants, alone or in combination, and certain opioid-based combinations may be effective for NCP based on current evidence, although the certainty of this evidence is low. Some plant-derived compounds also demonstrated potential analgesic effects, although these findings are exploratory and based on a limited number of trials, and further evidence is needed to verify their efficacy. Given the low certainty of most comparisons, clinicians should interpret these results cautiously and balance potential benefits with safety profiles when selecting treatments for NCP.
BACKGROUND:Postoperative pain is common among cardiac surgery patients, with some experiencing moderate to severe pain that persists for months. Photobiomodulation (PBM)-red light therapy, as a physical therapy, has been validated for promoting wound healing and alleviating neuropathic pain. This study aims to investigate the efficacy and safety of red light therapy in relieving acute postoperative pain in patients undergoing median sternotomy for cardiac surgery. METHODS:This single-center retrospective cohort study included 264 patients who underwent cardiac surgery at Nanjing Drum Tower Hospital between January 2024 and February 2025. Among them, 184 patients were used as the control group, and the patients in the control group did not receive red light therapy during their stay in the CICU, while 80 patients in the observation group received PBM within 2 h after entering the CICU on the day of surgery. The incidence of acute postoperative pain, critical-care pain observation tool (CPOT) scores, morphine milligram equivalents per kilogram (MME/kg), and wound healing outcomes were compared between the two groups. RESULTS:The incidence of acute pain was significantly lower in the observation group than in the control group (38.8% vs 57.1%, p < 0.05). Additionally, CPOT scores and MME/kg were significantly reduced in the observation group (p < 0.05). No significant differences were observed in postoperative drainage output or the incidence of poor wound healing between the two groups (p > 0.05). CONCLUSION:In this retrospective cohort, early application of red light therapy was associated with alleviated acute postoperative pain and reduced opioid consumption, with no observed increase in wound-related complications. These findings suggest that PBM may serve as a safe and effective nonpharmacological adjunct for postoperative pain management in cardiac surgery patients.
BACKGROUND:Patients with neuropathic pain frequently experience impaired sleep quality. The systemic immune-inflammation index (SII) is a readily available blood-based inflammatory marker, but its association with sleep disturbance in neuropathic pain patients remains insufficiently defined. METHODS:This single-center prospective longitudinal observational cohort study enrolled 135 patients aged 40-65 years with neuropathic pain confirmed by the DN4 questionnaire, disease duration of 6-12 months, and pain inadequately controlled by conventional medication. Baseline severe sleep disturbance was defined using a prespecified severity-based threshold of PSQI > 10. Fasting blood and first-morning spot urine samples were collected at baseline and at the 1-month follow-up after PRF. SII was calculated as platelet count x neutrophil count/lymphocyte count. Native urinary melatonin concentration was measured by ELISA and reported as an unadjusted spot urine concentration. The primary analysis evaluated the association between baseline SII and severe sleep-disturbance status; post-PRF changes were interpreted as within-subject temporal changes because no control group was included. RESULTS:At baseline, 73 of 135 patients met the prespecified criterion for severe sleep disturbance. Compared to the nonsevere group, the severe group had higher baseline SII (803.03 ± 111.45 vs. 604.21 ± 164.29, p < 0.001) and lower urinary melatonin concentration (8.32 ± 2.17 vs. 9.61 ± 2.72, p = 0.006). At the 1-month follow-up, severe sleep-disturbance status was present in 9 patients (McNemar test, p < 0.001). SII decreased, and urinary melatonin concentration increased in both baseline severity groups (all within-group p < 0.001). In a limited multivariable logistic regression model adjusted for available baseline covariates, baseline SII was associated with severe sleep-disturbance status (adjusted OR per 1-unit increase: 1.011; 95% CI: 1.007-1.014; p < 0.001). Exploratory ROC analysis yielded an apparent in-sample AUC of 0.833. CONCLUSIONS:Higher baseline SII was associated with severe sleep-disturbance status in this mixed neuropathic pain cohort. The observed longitudinal changes after PRF should be interpreted cautiously as within-subject temporal changes rather than PRF-specific effects. The findings are exploratory and do not establish causality, a direct inflammatory mechanism, or validated predictive performance. TRIAL REGISTRATION:Chinese Registry of Clinical Trials: ChiCTR2500103587.
Adhesive capsulitis causes severe shoulder pain and functional limitation, and single treatment modalities often fail to prevent relapse after manipulation under anesthesia. In this randomized controlled trial, we examined whether adding ultrasound-guided multitarget platelet-rich plasma injections to manipulation under brachial plexus block could improve pain, function, and health-related quality of life. We enrolled 68 adults with adhesive capsulitis confirmed by magnetic resonance imaging and randomly assigned them to manipulation plus standardized rehabilitation or to the same regimen plus pericapsular platelet-rich plasma injections at baseline, two weeks, and one month. Blinded assessors evaluated outcomes before treatment and at one day, 2 weeks, 1 month, and 3 months. The primary endpoint was shoulder pain on the visual analogue scale at end. Secondary endpoints included the Disabilities of the arm, shoulder, and hand questionnaire; the Oxford shoulder score, the 36-Item Short Form Health Survey; the Constant Murley shoulder score, and serum inflammatory marker levels. The combined strategy led to faster and more pronounced pain relief, with clinically meaningful differences between group immediately after treatment and at the 3-month follow-up. In addition, patients who received platelet-rich plasma showed greater gains in shoulder function and health-related quality of life, and a higher proportion of them reached predefined thresholds for clinically important improvement. Short-term changes in inflammatory markers were exploratory and nonspecific and should not be interpreted as evidence of a causal immunomodulatory effect. Taken together, these findings suggest that multitarget platelet-rich plasma combined with manipulation under brachial plexus block was well tolerated in this trial and was associated with significant short-term improvement in pain and function for patients with adhesive capsulitis.
PURPOSE:This study aims to examine the academic output, key research hotspots, collaborative networks, and trends in liposomal bupivacaine research using bibliometric methods. By providing a broad overview, we seek to clarify the knowledge structure and emerging trends in its clinical applications in perioperative analgesia. METHODS:We searched the Web of Science Core Collection database on November 4, 2025, to find relevant articles and reviews. Analytical tools such as CiteSpace and VOSviewer were used to evaluate publication years, countries/regions, institutions, journals, highly cited literature, terms, collaboration networks, and cocitation clusters. RESULTS:The dataset comprised 1,069 valid publications from 101 countries/regions, involving 3,256 institutions and 13,736 authors. The annual publication output grew slowly before 2015, increased rapidly after 2016, and reached a peak in 2021. The United States (US) was the leading contributor with 775 publications, followed by China with 155 publications. The Harvard University System and the University of Texas System were identified as central research institutions. Journal of Arthroplasty published the largest number of articles, while Anesthesia and Analgesia recorded the highest average citations per article. Term co-occurrence and burst analyses identified four major research clusters: formulation and pharmacological foundations, safety considerations, procedure-specific analgesia, and emerging regional anesthesia techniques. Recent research hotspots included erector spinae plane block, thoracic surgery, and paravertebral block, indicating a shift toward novel nerve block applications and complex surgical scenarios. CONCLUSION:Research on liposomal bupivacaine has evolved from formulation development to a clinically oriented field with strong interdisciplinary integration and expanding procedural applications. The US remained the leading contributor to global research and collaboration. These findings provide a structured overview of the evolving evidence base and might help guide future procedure-specific research and perioperative analgesia strategies.
BACKGROUND:Chronic migraine is a prevalent and disabling neurological disorder with substantial impact on patients' quality of life. Understanding the thematic structure and evolution of chronic migraine research is critical for guiding future studies and clinical practice. This study utilized cluster analysis to map research hotspots, thematic developments, and emerging trends in the global literature on chronic migraine. METHODS:Relevant publications on chronic migraine from 1917 to 2024 were retrieved from the Web of Science Core Collection. Bibliometric and cluster analyses were performed using VOSviewer, CiteSpace, and R 4.3.3, focusing on keyword co-occurrence, thematic clustering, and citation burst analysis to identify research hotspots and their evolution. RESULTS:A total of 6366 articles were included. Cluster analysis of high-frequency keywords identified five major research clusters: (1) Pathophysiological mechanisms and molecular targets, (2) epidemiology, comorbidities, and quality of life, (3) clinical trials and therapeutic strategies, (4) diagnosis and classification, and (5) regional and national burden. Thematic evolution analysis revealed a shift from early focus on epidemiology and symptomatology to recent emphasis on gene-related peptides, preventive therapies, and resistance mechanisms. Burst keyword analysis highlighted emerging topics such as "calcitonin gene-related peptide," "preventive treatment," and "central sensitization," reflecting a growing interest in novel biologics and mechanisms of treatment resistance. The United States led in publication volume and collaboration, with Headache, Cephalalgia, and Neurology as core journals and Harvard University and the Mayo Clinic as the leading institutions. CONCLUSIONS:Cluster analysis identified five core research areas in chronic migraine and revealed a shift from epidemiological description to molecular mechanisms and individualized treatment. Future research is likely to focus on integrating pharmacological and non-pharmacological interventions to further optimize patient outcomes.
BACKGROUND:Breakthrough cancer pain (BTcP) is a challenging symptom in lung cancer patients, often associated with poor physical and psychological outcomes. Understanding its clinical features and associated factors is essential for improving pain management and patient care. METHODS:This cross-sectional study prospectively enrolled lung cancer patients with BTcP treated at our center between October 2024 and January 2025. Data were collected through questionnaires and medical records, including demographic, clinical, psychological, and symptom-related variables. Logistic regression analysis was conducted to identify factors associated with BTcP severity. RESULTS:A total of 255 eligible patients were enrolled. BTcP was most commonly located in the chest (148/255, 58.0%) and frequently triggered by coughing (124/255, 48.6%). Most episodes were of short duration and moderate to severe intensity. Multivariate analysis identified treatment modality, cough VAS score, and anxiety level as independent associated factors of BTcP severity (p < 0.05). In the postoperative subgroup (n = 159), surgical extent, number of drain tube, cough VAS score, and anxiety level were significant factors for BTcP severity. CONCLUSIONS:BTcP in lung cancer patients is characterized by high frequency and moderate-to-severe intensity, with anxiety and cough being key contributing factors. Comprehensive pain management should integrate psychological support and symptom control to improve patient outcomes.
BACKGROUND:Chronic pain (CP) constitutes a multidimensional clinical phenomenon with rising prevalence globally, producing substantial societal and healthcare burdens. Metabolic and inflammatory dysregulations are central to its pathophysiology, stimulating interest in identifying biomarkers that reflect these underlying processes. The uric acid to high-density lipoprotein cholesterol ratio (UHR) serves as an integrated index representing systemic inflammatory status and lipid metabolism, offering potential relevance in CP research. METHODS:This cross-sectional study analyzed data from 12,012 adults aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 cycles. UHR was calculated as serum uric acid divided by high-density lipoprotein cholesterol. CP was defined as pain lasting ≥ 24 h during the previous month and persisting for ≥ 3 months. Associations between UHR and CP were evaluated using multivariable logistic regression models adjusting for demographic, metabolic, and clinical covariates. Restricted cubic spline and threshold-effect analyses were further performed to assess potential nonlinear relationships. RESULTS:Higher UHR levels were associated with increased CP prevalence. In the fully adjusted model, participants in the highest UHR quartile exhibited significantly greater odds of CP compared with those in the lowest quartile (OR = 1.44, 95% CI: 1.22-1.70). Continuous-variable analysis demonstrated that each unit increase in UHR was associated with an 11% increase in CP odds. Restricted cubic spline analysis revealed an approximately linear positive association between UHR and CP prevalence, whereas threshold-effect analysis did not identify a statistically significant nonlinear relationship. CONCLUSION:The findings indicate that UHR may serve as a biologically informative metabolic correlate of CP. While causality cannot be inferred due to the cross-sectional design, these results highlight a link between metabolic-inflammatory status and CP prevalence. Future longitudinal studies are required to clarify temporal dynamics and assess the predictive value of UHR.
OBJECTIVE:Research has emphasized the "phenotyping" of knee osteoarthritis (OA) pain as a priority to effectively target therapies to individual patients. This study identified pain phenotypes based on experimental pain responses in patients with symptomatic knee OA using machine learning approaches and examined their associations with participant characteristics. METHODS:In this cross-sectional study, participants (N = 208; mean age = 67.64 ± 7.51 years) completed demographic, clinical, and psychological questionnaires, followed by a multimodal quantitative sensory testing (QST) battery. For phenotyping, we implemented a two-layer neural network-based k-means algorithm. Participant characteristics were compared across phenotypes using analysis of variance (ANOVA). RESULTS:Five phenotypes were identified, with marked differences across QST measures: (1) "high pressure pain sensitivity and impaired descending inhibition" (n = 86), characterized by average responses on most QST measures, particularly low pressure pain threshold (PPTh) and impaired conditioned pain modulation (CPM), (2) "high heat pain sensitivity" (n = 40), marked by the lowest heat pain thresholds and tolerances, (3) "low pain sensitivity" (n = 46), exhibiting low sensitivity across most QST measures, (4) "high pain sensitivity and impaired pain modulation" (n = 26), with the lowest PPTh, highest punctate mechanical pain, greatest temporal summation of mechanical pain, lowest CPM, and highest cold pain sensitivity, and (5) "pain-resilient" (n = 10), characterized by low sensitivity across most QST measures, along with the highest PPTh and highest CPM. Phenotypes differed significantly by sex, Kellgren-Lawrence score (index knee), pain severity (Numeric Rating Scale), and OA-related symptoms (Western Ontario and McMaster Universities Osteoarthritis Index), particularly physical function (p < 0.05). CONCLUSIONS:This study identified distinct experimental pain phenotypes, each associated with unique demographic and clinical characteristics. These findings may inform the development of interventions tailored to specific pain profiles to improve pain management and functional outcomes in patients with symptomatic knee OA. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT04375072.
BACKGROUND:Clinical observations have suggested an association between a high-fat diet (HFD) and neuropathic pain (NP). Studies also revealed that maresin 1 (MaR1) can regulate macrophage phagocytosis, modulate tissue repair and inflammatory resolution, and influence the progression of NP. However, the specific regulatory mechanisms of MaR1 in HFD-induced NP remain unclear. OBJECTIVE:The aim of this study is to explore the effect of MaR1 on neuroinflammation in mice with NP induced by an HFD. METHODS:A tibial nerve crush model with a HFD was used to establish HFD-induced chronic pain. The paw withdrawal threshold (PWT), which reflects mechanical allodynia, was measured to evaluate changes in pain-related behavior. Immunofluorescence was used to detect the relative number of macrophages and microglia, and the expression of growth-associated protein 43 (GAP43), while qPCR was used to measure the levels of proinflammatory cytokines. RESULTS:HFD consumption exacerbates nerve injury-induced NP formation and upregulates GAP43 expression. Macrophage infiltration and proinflammatory cytokine expression were increased in the DRGs of HFD-induced nerve injury mice. Intrathecal injection of the specialized proresolving mediator MaR1 alleviated nerve injury-induced chronic pain and decreased GAP43 expression in HFD-fed mice. Furthermore, MaR1 decreased proinflammatory macrophage migration in the damaged tibial nerves and DRGs of HFD-induced nerve injury model mice. CONCLUSIONS:The specialized proresolving mediator MaR1 can reduce neuroinflammation and GAP43 expression in the DRG and injured nerve fibers and alleviate NP in HFD-fed mice.
PURPOSE:To investigate the association between purine metabolism-related genes and trigeminal neuralgia (TN) using multiomics approaches. METHODS:A multiomics summary-data-based Mendelian randomization (SMR) approach was applied to investigate associations between purine metabolism-related genes and TN. Genome-wide association study (GWAS) data from FinnGen R10 were integrated with blood-derived DNA methylation quantitative trait loci (mQTL), expression quantitative trait loci (eQTL), and protein quantitative trait loci (pQTL) datasets. Associations were evaluated by colocalization and replication in UKBB (G6_TRINEU) and FinnGen R12. Drug-target MR analysis used blood eQTL variants as proxies for gene expression. GEO transcriptomic and single-cell RNA sequencing (scRNA-seq) datasets and GTEx brain tissue eQTL data provided expression and tissue-level validation. Functional enrichment, protein-protein interaction network, and druggability analyses were performed. RESULTS:SMR analysis identified 238 mQTLs (127 genes), 30 eQTLs, and 3 pQTLs associated with TN. Colocalization supported 96 mQTLs (23 genes), 18 eQTLs, and 3 pQTLs, with 42 mQTLs and the CNOT7 eQTL validated in UKBB. POMGNT2 showed genetically predicted associations with TN at both gene and protein levels. Integrative analysis highlighted ATP6V0E2, PLAT, and VKORC1 with evidence of epigenetic regulation. Drug-target MR provided supportive evidence that genetically proxied expression of CNOT7 and PLAT may be associated with lower TN risk. Transcriptomic validation showed downregulation of ATP6V0E2, PLAT, and CNOT7 after trigeminal nerve injury. Brain eQTL analysis supported the association of CNOT7 with TN across multiple brain regions. scRNA-seq revealed cell-type-specific expression patterns of prioritized genes in trigeminal ganglion tissues. Functional enrichment indicated involvement in stress response, metabolism, and genome maintenance pathways. PPI analysis identified six hub genes: ABCB1, COMT, GFM1, MDH2, NRAS, and TXN. Druggability analysis showed that ATP6V0E2, PLAT, and VKORC1 are targetable by existing drugs. CONCLUSION:This study prioritizes purine metabolism-linked genes showing genetically supported associations with TN and highlights potential biological pathways and therapeutic targets.
BACKGROUND:Musculoskeletal pain (MSP) is among the most common occupational health problems for nurses. The purpose of this study was to evaluate the prevalence and severity of work-related MSP in clinical nurses. METHODS:This cross-sectional and descriptive study was conducted with individuals who had been working as clinical nurses for at least 6 months. The study included 312 clinical nurses who were directly involved in patient care and met the eligibility criteria. Clinical nurses were assessed with the Ergonomic Risks Questionnaire (Ergo-Nurse), and work-related MSP was assessed with the Cornell Musculoskeletal Disorder Questionnaire (CMDQ). Spearman correlation, independent samples t-test, and hierarchical regression analysis were used to determine the relevant factors. RESULTS:Work-related MSP is a major health problem in clinical nurses, with MSP severity ranging from low lumbar > back > neck. Hierarchical regression analysis showed that biomechanical factors were the most important ergonomic factor associated with work-related MSP in clinical nurses (R2 Change: 17.178 p < 0.05), and other ergonomic subdimensions did not contribute significantly to the model (p > 0.05). In the gender variable, being female was found to be a significant risk factor for work-related MSP (p < 0.05). CONCLUSIONS:Biomechanical ergonomic risks and female sex were the main factors associated with work-related MSP among clinical nurses. These findings highlight the need for targeted ergonomic interventions, safe patient-handling practices, workload regulation, and institutional strategies to reduce musculoskeletal strain in clinical nursing settings.
BACKGROUND:Epidemiological data show that approximately 80% of cancer patients experience pain of varying degrees throughout the course of their disease, with nearly one-third experiencing severe pain, significantly impacting their quality of life and the effectiveness of antitumor treatment. Triple-negative (TN) breast cancer tissues typically exhibit increased stromal stiffness and abnormally elevated mechanical stress; these biomechanical alterations may amplify pain signals by activating mechanosensitive channels. Utilizing single-cell RNA sequencing analysis, this study aims to elucidate the potential biological links between fibroblast mechanotransduction and cancer-associated pain, thereby providing a theoretical basis for clinical diagnosis and treatment. METHODS:Dimensionality reduction and unsupervised clustering were used to identify cell types in TN breast cancer single-cell RNA sequencing data. To assess the association between pain and mechanical stimulation, we constructed a set of gene signatures associated with mechanical stimulation and pain and calculated scores using the Area Under the Curve Cell (AUCell). CellChat and SCENIC were used to reveal the communication networks and transcription factor regulatory mechanisms of fibroblast subtypes. RESULTS:COL3A1+ fibroblasts derived from TN breast cancer are highly involved in biological processes such as extracellular matrix remodeling, collagen fiber formation, and mechanotransduction. To assess the association between pain and mechanical stimulation, we constructed a gene signature set related to mechanical stimuli and pain and calculated corresponding scores using the AUCell tool. Cell communication studies showed that COL3A1+ fibroblasts interact extensively with epithelial cells and other cells through laminin and collagen signaling pathways, potentially leading to mechanotransduction remodeling of the TN breast cancer microenvironment. CONCLUSION:COL3A1+ fibroblasts demonstrate enhanced transcriptional profiles pertinent to collagen deposition and cytoskeletal reorganization, which are correlated with mechanotransduction signaling and may be connected with mechanical sensitivity in cancer-related pain. This study systematically characterizes the potential relationship between fibroblast-associated mechanotransduction characteristics and pain-related gene signatures at the single-cell level in TN breast cancer. These findings offer hypothesis-generating insights into the molecular landscape of tumor-associated pain, although additional experimental and clinical validation is necessary.
BACKGROUND:Neurophysiological assessments might advance the understanding of nonspecific chronic low back pain (nsCLBP) by quantifying altered pain processing and associated autonomic responses. Contact heat-evoked potentials (CHEPs) and sympathetic skin responses (SSRs) were compared between nsCLBP patients and healthy controls (HCs), and their relationships with experimental and clinical pain ratings were explored. METHODS:A total of 56 nsCLBP patients and 40 age- and sex-matched HCs were included in this study. All participants underwent simultaneous recordings of CHEPs and SSRs in response to two blocks of 15 heat stimuli applied at the back (i.e., the patients' clinical pain area) and the hand (nonpainful control area). Participants rated the perceived pain intensity of each contact heat stimulus using a numerical rating scale (0-10). The change of pain ratings, CHEP, and SSR amplitudes between blocks was calculated as habituation index. RESULTS:SSR latencies were prolonged in patients compared to HCs (F = 9.5, p = 0.003) and were shorter after back stimulation compared to hand stimulation (F = 9.6, p < 0.001). No other group differences were observed. Clinical pain intensities in patients correlated (1) with contact heat pain ratings in both areas (back: rho = 0.27, p = 0.041, control area: rho = 0.272, p = 0.042) and (2) inversely with CHEP P2 latencies after hand stimulation (current pain: rho = -0.324, p = 0.019; average 4 weeks: rho = -0.320, p = 0.022). CONCLUSION:Prolonged SSR latencies in nsCLBP might indicate a dysregulated pain-autonomic response. TRIAL REGISTRATION:Clinicaltrials.gov_identifier: NCT04433299.
BACKGROUND:Prolonged computer use among office workers leads to postural disorders and musculoskeletal pain, particularly in the neck region. Pilates exercises and kinesiotaping are widely used interventions for the management of chronic neck pain. AIMS:This study aimed to investigate the effects of Pilates exercises and kinesiotaping on neck pain, disability, cervical range of motion (CROM), neck muscle strength and core endurance in office workers with chronic neck pain. METHODS:A randomised controlled trial was conducted with 30 office workers who completed the intervention. Participants were randomly assigned to either a Pilates group (n = 16) or a kinesiotaping group (n = 14). Both groups participated in an 8-week, supervised Pilates programme, while the kinesiotaping group additionally received kinesiotaping applications to the cervical region. Assessments of neck pain, disability, CROM, muscle strength and core endurance were conducted pre- and postintervention. RESULTS:Both groups demonstrated significant improvements in pain, disability, CROM, neck muscle strength and core endurance (p < 0.05). Between-group comparisons revealed no significant differences in pain and disability outcomes (p > 0.05). However, an additional improvement in left cervical rotation CROM was observed in the kinesiotaping group (p = 0.001). CONCLUSIONS:Eight weeks of Pilates training significantly improved pain, disability and functional outcomes in office workers with chronic neck pain. Kinesiotaping provided limited additional benefits, primarily in rotational movements. From an occupational rehabilitation perspective, Pilates-based exercises may support work-related functional capacity and sustained work participation in sedentary occupations, while kinesiotaping may serve as a complementary modality. Further studies with larger samples are warranted to confirm these results. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT06262997.
