<h2>Abstract</h2><h3>Background</h3> Childhood cancer survival rates have improved over the last decades. Nevertheless, childhood cancer treatment is associated with painful interventions needed for disease monitoring or treatment. It is therefore crucial to ensure appropriate pain control for painful interventions. This European survey aims to map the approaches to manage such interventions in children and adolescents with cancer. <h3>Methods</h3> An online survey was sent to members of the European Society of Paediatric Oncology, asking the way potentially painful interventions are being managed. Interventions included lumbar puncture, bone marrow aspiration and biopsy, removal of drainages, insertion and removal of central venous lines, puncture of porth-a-cath or Ommaya reservoir, tumour biopsy, and insertion of nasogastric tube. Proposed approaches to pain management included local analgesia, systemic analgesia alone, systemic analgesia with sedation administrated by paediatric oncologists or anaesthesiologists, distraction techniques, and other methods. We further asked about drugs used and types of distraction. <h3>Results</h3> A total of 326 health care professionals responded, representing 37 countries. The proportion of participants reporting that an intervention is performed without any pain management ranged from one participant each for bone marrow aspiration/biopsy and tumor biopsy (0,3%), to 101 participants (31%) for nasogastric tube insertion. The intensity of analgesia or depth of sedation per intervention is heterogeneous, so are the drugs used. <h3>Conclusion</h3> The heterogenous results in use of analgesia or sedation during procedures indicate an unmet need. These results highlight the need for guidelines and their implementation in clinical practice. No child or adolescent undergoing cancer treatment should suffer from procedure-related pain.

Therapeutic potential of biased μ-opioid receptor agonists for delaying opioid tolerance in chronic pain management.

Tailoring of a chronic pain self-management intervention for individuals with opioid use disorder in office-based addiction treatment.

A Framework for Precision and Pragmatism for the Evaluation and Treatment of Venous-Origin Chronic Pelvic Pain.

Mu-opioid receptor (MOR) agonists remain the mainstay treatment for severe acute pain but are limited by adverse effects including respiratory depression and constipation. Compounds with improved therapeutic profiles have been reported, and reduced intrinsic efficacy has been proposed as one factor contributing to greater separation between antinociceptive and adverse effects. To investigate the contribution of receptor reserve and intrinsic efficacy to the in vivo effects of opioid agonists, we used the pseudo-irreversible MOR antagonist methocinnamox (MCAM) to progressively deplete functional MORs and examined the effects of three MOR agonists-morphine, 7-OH mitragynine, and tianeptine-across multiple behavioural assays in mice. MCAM pretreatment inhibited agonist-induced effects in a dose-dependent manner across all assays. Lower doses of MCAM preferentially attenuated the antinociceptive, forced swim, and gastrointestinal effects of the lower-efficacy agonist 7-OH mitragynine, consistent with increased sensitivity of these behaviours to receptor depletion. In contrast, locomotor activation and respiratory depression induced by all three agonists were inhibited by similar MCAM doses, indicating comparable susceptibility to receptor depletion despite differences in intrinsic efficacy. Together, these findings suggest that differences in functional receptor reserve contribute to some, but not all, MOR-mediated behavioural outcomes. While reduced intrinsic efficacy and receptor reserve can partially explain separation between antinociception and certain adverse effects, additional ligand-dependent factors likely influence the expression of specific opioid-induced behaviours in vivo.

Accurate diagnosis and treatment of zoster-associated pain (ZAP) remains challenging because identifying the affected dorsal root ganglion (DRG) relies on subjective assessment and lacks objective imaging. We developed and validated a quantitative model using neurological magnetic resonance imaging (MRI) and radiomics, with the contralateral healthy DRG as an internal control. This study aimed to identify imaging biomarkers for precise localization, optimized treatment, and improved patient prognosis. Clinical data were retrospectively collected from patients with ZAP who underwent neuro-magnetic resonance imaging (MRI) at the Pain Department of the First Affiliated Hospital of Fujian Medical University (December 2023-December 2024). T2-weighted neuroimages were acquired for region-of-interest segmentation. Experienced radiologists manually segmented neuropathic DRG by using the Insight Segmentation and Registration Toolkit Segmentation and Neuroimaging Applications Platform (ITK-SNAP), and quantitative radiomic features were extracted via PyRadiomics. Feature selection was performed using the Mann-Whitney U test and least absolute shrinkage and selection operator. The selected features were used to train Logistic Regression, Support Vector Machine, Neural Network, XGBoost, and AdaBoost models. Performance metrics included area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Overall, 408 DRGs from 68 patients (30 male, 38 female; mean age 68.25 ± 9.01years) were analyzed. From 1316 radiomic features per region, 10 robust and discriminative features were retained for model construction. The neural network achieved the highest diagnostic performance in the training and validation set (AUC 0.818; 95% confidence interval: 0.719-0.916, p = 0.001). Decision curve and calibration analyses indicated moderate clinical utility in distinguishing affected from healthy DRGs. Magnetic resonance imaging-based radiomics using a neural network algorithm robustly discriminates lesioned dorsal root ganglia in zoster-associated pain. This approach provides an objective imaging tool to improve diagnostic precision and guide targeted therapy.

Microsurgical dorsal root entry zone (DREZ) lesioning is an established treatment for refractory pain following brachial plexus avulsion. However, lesion depth and trajectory are critical technical variables that may influence safety and outcomes. We report our single-center experience using intraoperative ultrasound for systematic post-lesion confirmation during cervical DREZ lesioning. Between January 2016 and March 2025, 23 consecutive patients with complete or partial brachial plexus avulsion and severe neuropathic pain (VAS ≥6) refractory to optimized pharmacological therapy underwent cervical DREZ lesioning with ultrasound-based post-lesion confirmation. Serial microcoagulations were performed along the posterolateral sulcus to a depth of approximately 3 mm with medial angulation of 25°-45°, under multimodal neuromonitoring. Ultrasound was used after each lesion to confirm depth and medial-lateral trajectory. Pain intensity was assessed using the visual analog scale (VAS) at baseline and during serial follow-up. Mean preoperative VAS was 9.6. At a median follow-up of 36 months (range: 6-108), 13 patients (57%) achieved excellent pain relief (VAS ≤3), 6 (26%) had good relief (VAS: 4-6), and 4 (17%) had poor outcomes (VAS ≥7). One patient (4%) developed a transient motor deficit lasting three months, 2 (9%) required revision for laminotomy reconstruction subsidence, and 1 patient (4%) died from postoperative pulmonary embolism. Intraoperative ultrasound for post-lesion confirmation during cervical DREZ lesioning is feasible and may enhance depth and trajectory verification. Durable pain relief was achieved in the majority of the patients. Further studies are needed to define its incremental benefit.

Effectiveness of exercise therapy versus passive conservative treatments for rotator cuff-related shoulder pain: a systematic review and meta-analysis of randomized controlled trials.

The Society of Interventional Radiology Practice Guidance Document on Venous-Origin Chronic Pelvic Pain in Women.

Exercise is a well-established treatment for chronic low back pain (LBP), yet its effects on inflammation remain unclear. Examine the effects of running on inflammatory markers in chronic LBP and its associations with pain intensity, and mental health as an a priori secondary analysis. An a priori secondary analysis of a 12-week, two-arm, parallel-group randomised controlled trial was conducted. Forty adults with chronic LBP were randomised to a run-walk program or waitlist control. The intervention was a digitally delivered, remotely supervised run-walk program, prescribed three times per week for 30min. Outcomes assessed included systemic inflammatory markers (C-reactive protein [CRP], interleukin-8 [IL-8], and tumour necrosis factor alpha [TNF-α] as well as pain intensity (Visual Analogue Scale), and mental health (21-item Depression, Anxiety, and Stress Scale). No significant between-group differences were observed in CRP (ß [95% CI]=0.34 [-0.07, 0.74] (log-transformed scale), p=0.109), TNF-α (-1.29 [-6.15, 3.58] pg/mL, p=0.595), or IL-8 (-0.36 [-1.30, 0.58] (log-transformed scale), p=0.443) over the 12 weeks. The associations between changes in inflammatory markers and pain intensity or mental health were not different between groups (all p>0.05). A 12-week run-walk training did not alter systemic CRP, TNF-α, or IL-8 in adults with chronic LBP. Improvements in pain intensity were not associated with changes in these inflammatory markers. Clinically, this intervention offers a low-cost and accessible approach that provides meaningful improvements in chronic LBP without observed changes in systemic CRP, IL-8, and TNF-α.

Gabapentin loaded nano-emulsion for the effective treatment of peripheral neurological pain: Formulation, characterization, and ex vivo studies

Noninvasive detection of chronic pancreatitis (CP) is important for proper treatment and prevention of severe pain and pancreatic insufficiency. To evaluate if T1ρ MRF is significantly different in healthy volunteers and patients with CP. Prospective. Seventeen healthy volunteers (9 male, mean age: 38.0 ± 6.7 years) and 20 patients (12 male, mean age: 53.6 ± 6.4 years) who were clinically diagnosed with CP. 3 T, T1ρ MRF acquired during breath-hold (BH-MRF) and free breathing (FB-MRF), conventional T1/T2 mapping sequences. Mean T1/T2/T1ρ values in the whole pancreas were compared between diagnosed CP patients and controls. The Cambridge classification (CC) score was used to divide patients into mild-moderate (CC = 1-3) and severe (CC = 4) CP subgroups. T1, T2, and T1ρ relaxation maps were generated from both breath-hold (BH) and free-breathing (FB) MRF data. Mixed effects models were calculated for healthy control versus CP, and between mild-moderate and severe CP. Receiver operator characteristic (ROC) curves were analyzed and areas under the curves (AUCs) were calculated. A p-value < 0.05 was considered significant and multiple comparison corrections were applied. BH-MRF T1/T2/T1ρ values were significantly higher in the CP group (1327.3, 48.6, 49.1 ms) compared to healthy controls (821.6, 41.6, 39.5 ms) with AUCs of 0.994, 0.873, and 0.862, respectively. The MRF BH T1/T2/T1ρ values of mild-moderate CP (N = 7) and severe CP (N = 13) patients were also significantly higher compared to healthy controls. T1 was significantly higher in severe CP compared to mild-moderate CP (1497 and 1012.1 ms, respectively) with AUC = 0.945. FB MRF T1 relaxation times demonstrated good correlation with BH values (0.981), while T2 and T1ρ had moderate correlations (0.507 and 0.697, respectively). T1, T2, and T1ρ relaxation times have potential for noninvasively assessing CP. 2. Stage 2.

Cornuside alleviates microglia-mediated neuroinflammation to ameliorate chronic neuropathic pain-induced cognitive impairment via the Nrf2/Sirt3 signaling pathway.

A study on the network pharmacology of HQGZWWT that prevents CINP by inhibiting ferroptosis through regulation of the p38/c-FOS/NF-kB pathway.

Osteopathic manipulative treatment, pain neuroscience education and clinical hypnosis as pain management interventions in chronic low back pain: a randomized sham-controlled feasibility pilot trial.

Approximately 20% of youth undergoing major surgery develop chronic postsurgical pain (CPSP). However, preventive interventions for CPSP have yielded mixed results, partly due to the limited involvement of patients and caregivers in the intervention development process. Single-session interventions (SSI) are well-suited in this context, as they are time- and cost-efficient. This study investigates the perioperative needs of patients and caregivers, and utilizes these insights to co-develop a preventive psychological SSI for post-surgical pain. Two rounds of focus groups were conducted with patients and caregivers to (1) gather information on the perioperative experience of patients and caregivers to develop the content of a preventive SSI, and (2) gather feedback on the draft of the intervention. Participants' experiences were analyzed applying structural content analysis. Based on these results, the content of a digital intervention was developed, which was then presented to participants for evaluation, and feedback was analyzed using participatory observation. Five adolescent patients and four mothers took part in the focus groups. In total, 5 superordinate categories were identified: Consequences of context (i.e., contextual components), looking after yourself (i.e., self-care related components), limitations of healthcare system (i.e., healthcare system-based components), requests for medical staff (i.e., specific expectations directed toward providers) and child as primary focus (i.e., child-focused components). The intervention draft was well accepted by participants, and minor suggestions for improvement were implemented. Our study identifies core topics of importance for patients undergoing major surgery and their caregivers, and informs the development of a preventive psychological intervention.

Pilot Randomized Controlled Trial of Krill Oil Supplementation for Chronic Musculoskeletal Pain in Older Adults.

Racial, ethnic, and socioeconomic disparities in pain severity and treatment persist across healthcare settings, reflecting inequities shaped by patients' experiences of discrimination and bias. Perceived healthcare discrimination (PHCD), feeling dismissed, disrespected, or treated unfairly by healthcare providers, may contribute to persistent pain disparities among socially disadvantaged populations, yet its independent role relative to everyday discrimination remains underexplored. Using cross-sectional data from the All of Us Research Program, we examined associations between PHCD and pain severity among 89,069 participants from the Registered Tier Dataset (v7, R2022Q4R9), excluding individuals with missing data or non-categorized racial identities. Multinomial logistic regression models adjusted for age, sex, race/ethnicity, income, and education were used to estimate odds ratios (ORs) for pain severity. Both occasional and frequent PHCD were significantly associated with higher odds of mild, moderate, and severe pain (all p <.001). Participants reporting frequent PHCD had nearly eightfold higher odds of severe pain compared with those reporting no discrimination (OR = 7.98, 95% CI: 6.85-9.30). These associations persisted after full covariate adjustment, demonstrating a clear dose-response relationship between discrimination frequency and pain severity. PHCD emerged as a robust and independent predictor of pain severity in a large, diverse national sample, highlighting discrimination as a modifiable social determinant of pain and underscoring the need for equity-focused clinical communication and systemic interventions to improve pain management. PERSPECTIVE: This study, the largest to date examining perceived healthcare discrimination, demonstrates a significant association with greater pain severity across diverse populations. Highlighting a critical social determinant of health, these findings underscore the importance of addressing discrimination within clinical care. Integrating equity-focused strategies into pain assessment and management is essential to reduce disparities and improve outcomes among marginalized communities.

The objective of this study was to utilize real-world data from National Poison Data System (NPDS) to evaluate the relative risk of intentional use and subsequent outcomes following exposures to buprenorphine buccal film (BBF) compared to immediate-release (IR) and extended-release (ER) full agonist opioid (FAO) formulations, and buprenorphine transdermal patch (BTP). A cross-sectional study design compared exposures that involved BBF to those that involved IR FAO, ER FAO, and BTP using real-world data from NPDS. Data included individuals age 18years and older involved in exposures managed by US poison centers from 2020 to 2023. Descriptive statistics were used to summarize study groups, exposures, and outcomes. Relative risk was calculated for exposure reasons and clinical outcomes using BBF as reference group. Dataset included 276 BBF, 43,322 IR FAO, 2453 ER FAO, and 134 BTP exposures. Compared to BBF, significantly higher risks were found for both IR FAO and ER FAO for intentional abuse, intentional suspected suicide, significant medical outcome, hospital admission, and treated/evaluated and released level of care. Findings from this study suggest that, compared to FAO, exposures to BBF managed by US poison centers were less likely to involve intentional abuse or suspected suicide, have a decreased risk of resulting in a life-threatening effect or death, and have a lower likelihood of subsequent hospital admission and emergency department visits. Along with published guidelines and medication labels (including boxed warnings), relative risks of intentional exposures and associated clinical outcomes should be considered when determining opioid therapy for pain management.

People with IA may suffer from pain of differing aetiologies and subtypes including nociceptive joint pain, neuropathic pain of carpal tunnel syndrome or nociplastic pain from concomitant fibromyalgia. Lack of precise measurement tools to identify nociplastic pain influences as a contextual factor potentially all outcomes in collected clinical trials as residual pain might impact various measurements in IA. The OMERACT 2025 pain SIG discussed, developing a scoping review from protocol, to identify an instrument to measure nociplastic pain in IA and a contextualised domain definition for nociplastic pain in IA. Stakeholder opinions were sought regarding pain in IA and the importance of identifying an instrument to measure nociplastic pain in IA. A total of twenty-four participants attending the OMERACT 2025 pain SIG session included a mix of patients, clinicians, researchers, methodologists, and industry representatives. Patient research partner (PRP), MC spoke about the impact of pain including different pain subtypes in IA. She recapped the results of OMERACT 2023 poll where participants, including PRPs, agreed that assessing different pain subtypes in IA was important to improve targeted treatments for pain. SK - a pain specialist- presented evidence supporting the presence and impact of nociplastic pain in different IA's including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (AxSpA). Details of the scoping review protocol developed by the OMERACT Pain Working Group identifying candidate instruments for nociplastic pain assessment in IA was presented. Participants opinions were polled regarding their perspectives of the nociplastic pain definition and measurement. Polling showed clear agreement on advancing efforts to identify or develop an outcome measure for nociplastic pain. Most participants (86 %, 19/24) endorsed beginning with a systematic review of the existing literature to identify an appropriate validated instrument. Following a pain neuroscience education session five of the six (83 %) patient research partners (PRP) agreed they would be able to report the different pain types experienced in IA. Only one participant (1/24) agreed that the current IASP nociplastic pain definition is directly applicable to IA. Most participants (96 %) either disagreed or were uncertain, and over half (14/24) felt the definition likely requires contextualisation for IA. There was broad agreement that, in a substantial proportion of patients with inflammatory arthritis, nociplastic pain persists despite optimal treatment, is challenging to manage in routine clinical practice, and is associated with substantial patient suffering. The OMERACT meeting underscored the need for a standardized measure of nociplastic pain in inflammatory arthritis to refine eligibility criteria and support the development of stratified approaches in future clinical trials.