Chronic pain is increasingly recognised as a standalone medical condition shaped by interacting biological, psychological, and social determinants, affecting nearly one in three adults worldwide. This review synthesises contemporary evidence on the epidemiology, mechanisms, and management of chronic pain, with emphasis on the convergence of genetic, neurobiological, and psychosocial factors. We draw on recent population-based studies, clinical trials, neuroimaging research, and multi-omic genetic analyses to highlight the complexity and heterogeneity of this condition. Chronic pain disproportionately affects older adults, women, and socioeconomically disadvantaged groups, and frequently co-occurs with psychiatric, cardiovascular, and neurodegenerative disorders, reflecting shared pathways of maladaptive neuroplasticity. Although pharmacological therapies often provide modest long-term benefit, integrated psychological, physiotherapeutic, and interventional approaches demonstrate more sustainable improvements in function and quality of life. Advances in genomics and large-scale genome-wide association studies (GWAS) have revealed extensive polygenic overlap with psychiatric and immune traits, while neuroimaging consistently demonstrates alterations within prefrontal, insular, and limbic circuits that shape pain perception and persistence. Despite reliance on subjective symptom reporting, emerging digital phenotyping, wearables, and AI tools offer promising avenues for objective monitoring and personalised treatment. Integrating biological, behavioural, and environmental data will be essential to achieving truly precision-based chronic pain care.

Introduction Anxiety is common in patients with cancer-related pain, affecting an increasing number of individuals annually and negatively impacting prognosis. Limited methods are available for early identification of anxiety in these patients. This study explores the link between the OPRM1 gene's polymorphism and anxiety in cancer patients. Methods We prospectively recruited 76 patients experiencing pain from Yunfu People's Hospital and assessed them with questionnaires on anxiety, depression, quality of life, and other metrics before they commenced opioid treatment. Additionally, Numeric Rating Scale (NRS) scores and opioid usage data were recorded. In situ hybridization was used to analyze the OPRM1 polymorphism rs1799971. Based on the available data, appropriate opioid dosage conversion relationships were established. Results This study found that 40.8% (31/76) exhibited anxiety symptoms. OPRM1 genotyping revealed 31.6% AA, 48.7% AG, and 19.7% GG genotypes, conforming to Hardy-Weinberg equilibrium. No genotype differences were found in morphine dosage or NRS pain scores. However, G allele carriers exhibited significantly lower anxiety scores (median 27.0 vs. 36.0, p = 0.017). Multivariate analysis identified G allele (OR = 0.15, p = 0.040) and antitumor therapy (OR = 0.10, p = 0.027) as protective against anxiety, while breakthrough pain (OR = 6.65), higher pretreatment NRS scores (OR = 2.80), and depression (OR = 61.03) were risk factors (all p < 0.05). Discussion Our study indicates that G allele carriers exhibit lower anxiety levels, suggesting a certain correlation between the OPRM1 gene polymorphism and anxiety in cancer pain patients. Furthermore, there is a need to pay increased attention to the psychological health of cancer pain patients with the AA genotype.

Current treatment options for acute and chronic pain provide limited efficacy and safety. There is an urgent need to develop drugs with new, non-opioid treatment strategies that produce fewer adverse consequences. Preclinical evidence across multiple models of acute and chronic pain demonstrate that (2R,6R)-Hydroxynorketamine [(2R,6R)-HNK], a nonhallucinogenic metabolite of ketamine, promotes potent and long-lasting analgesic effects. This review summarizes the growing evidence for the analgesic action of (2R,6R)-HNK in rodent models of acute and chronic pain. (2R,6R)-HNK produces antinociceptive effects in studies using standard tests for acute pain such as the hot plate test, although not in all studies, as well as reversal of mechanical hypersensitivity in models of acute pain like the carrageenan model (inflammatory pain). However, the most consistent anti-allodynic effects are seen in animal models aimed at mimicking chronic pain conditions, such as models of neuropathic pain (Spared Nerve Injury and Chemotherapy-induced peripheral neuropathy), low-back pain (disc puncture), complex regional pain syndrome type-1 (tibial fracture) and chronic primary pain (low-frequency percutaneous electrical nerve stimulation). Unlike ketamine, doses of (2R,6R)-HNK that counteract pain hypersensitivity do not cause sedation, dissociation, or sustain self-administration associated with abuse liability. Furthermore, distinct pharmacological effects of (2R,6R)-HNK, longer functional duration of action, non-opioid-mediated analgesia, and glutamatergic-mediated mechanisms, may distinguish (2R,6R)-HNK from ketamine and other analgesic drugs and contribute to the treatment of acute and chronic pain.

Background Effective postoperative pain (POP) management is crucial to enhance satisfaction and recovery. Nurses play a significant role in providing effective pain management, making it crucial to assess their practices. However, most prior research in Ethiopia relied on self-administered tools to evaluate nurses' POP management, potentially introducing bias. This observational study addressed this gap by exploring POP management practices and associated factors among nurses in public hospitals in the West Shewa zone. Method and materials A facility-based cross-sectional study incorporating both self-reported and observed quantitative measures was conducted among 377 randomly selected nurses in public hospitals in the West Shewa zone, Ethiopia, from June 1 to August 30, 2020. Data were collected using a standardized interviewer-administered questionnaire and an observational checklist. Non-participant observation was done three times by trained BSc degree nurses. Data quality was ensured, and analysis was done using SPSS version 26. The logistic regression analyses were done to identify factors independently associated with nurses' POP management practice. Adjusted odds ratio (AOR) with 95% CI was estimated to measure the strength of the association. The level of statistical significance was set at a p value <0.05. Result Only 25.72% (95% CI: 23.4–32.6) of observed nurses demonstrated good postoperative pain management practices. Factors significantly associated with good practice included being female [AOR: 2.56, 95% CI: 1.78–4.79], using standardized pain assessment tools [AOR: 2.94, 95% CI: 1.65–5.86], working in hospitals with pain management policies [AOR: 3.10, 95% CI: 1.65–5.86], employment in surgical units [AOR: 2.93, 95% CI: 1.27–6.80], and having received relevant training [AOR: 2.28, 95% CI: 1.46–7.40]. Conclusion Only a quarter of nurses demonstrated good postoperative pain management practices. Female nurses, use of standardized pain assessment tools, presence of formal hospital pain management policies, work in surgical units, and prior training were key enablers. To improve practice, hospitals should provide regular in-service training focused on evidence-based postoperative pain assessment and intervention, implement standardized pain assessment tools, and enforce comprehensive institutional policies guiding pain management across all wards.

Background Patients commonly experience chemotherapy-induced peripheral neuropathy (CIPN) as an adverse effect from chemotherapies, such as taxanes. In some patients, CIPN symptoms are severe and significantly impact their quality of life. Gaining a deeper understanding of how patient factors change over time, and identifying predisposing patient factors for CIPN susceptibility, could provide opportunities to mitigate the risk of CIPN and improve patient outcomes. Methods A total of 229 patients with breast cancer receiving taxane chemotherapy completed study visits over 12 months. Data from patient reported outcomes (PROs) were collected from validated questionnaires to assess CIPN, anxiety, depression, weight, physical function, and sleep disturbance. Wilcoxon signed-rank tests were conducted to evaluate changes in PROs between timepoints (pre-treatment, on-treatment, post-treatment). Logistic regression was used to compare PROs between CIPN and non-CIPN groups at each time point, after adjustment for age, race, and pre-treatment CIPN score. Results were adjusted for multiple comparisons using a false discovery rate (FDR) procedure (FDR P < .05). A random forest model using 19 patient features was employed to build a CIPN predictive model. Results Out of 229 patients, 75% developed CIPN. Higher depression scores were associated with CIPN development across the three time periods: pre-treatment (OR = 1.20, FDR P = 5.3 × 10 − 3), on-treatment (OR = 1.32, FDR P = 4.4 × 10 − 4), and post-treatment (OR = 1.24, FDR P = 4.3 × 10 − 3). Similarly, pre-treatment PROMIS physical function T scores were lower among patients who developed CIPN (FDR P = 1.30 × 10 −2 ), on-treatment (FDR P = 5.78 × 10 −6 ) and post-treatment (FDR P = 8.7 × 10 −5 ). On treatment anxiety scores were higher on-treatment in patients experiencing CIPN (OR = 1.30, FDR P = 4.3 × 10 −3 ). Patients with obesity were 3.78 times more likely to develop CIPN compared to those with normal weight (FDR P = 3 × 10 −3 ). Patients with CIPN did not report experiencing higher levels of sleep disturbance (FDR P > .05). The random forest predictive model reached an accuracy of 84% with body mass index (BMI), physical function score and general anxiety score as the most important predictors. Conclusion These findings indicate that those experiencing CIPN were more likely to report reduced physical functioning, increased anxiety and depression, and have higher BMIs. As new multi-modal approaches are developed for CIPN, pre-treatment physical functioning, BMI and other patient reported measures may provide predictive ability.

Chronic pain—including both chronic primary pain (e.g., headaches, widespread musculoskeletal pain, abdominal pain) and chronic secondary pain associated with other health conditions—represents a significant yet underrecognized health concern among transgender and gender-diverse (TGD) youth. While data on the prevalence of chronic pain in TGD youth remain limited, early studies indicate higher rates compared to their cisgender peers, highlighting the need for understanding factors underlying this co-occurrence. Chronic pain arises from a complex interplay of neurobiological, psychological, and social factors, and its heightened prevalence in TGD youth may be driven by the compounded impact of biopsychosocial stressors that disproportionately affect this group. This review summarizes neurobiological vulnerabilities, psychosocial factors, and societal and systemic barriers that may contribute to increased risk of chronic pain in TGD youth. We also examine the role of gender-affirming care in addressing these biopsychosocial vulnerabilities and explore its potential to alleviate some of the factors associated with chronic pain. Additionally, we identify critical gaps in the current body of research, such as the need for longitudinal studies and deeper exploration of the effects of medical interventions like pubertal suppression and exogenous hormones on chronic pain mechanisms and outcomes. By synthesizing the available evidence, we aim to guide future research and offer actionable recommendations to enhance clinical care and support for TGD youth experiencing chronic pain.

Objective To develop a position statement based on expert opinions for the management of medication overuse headache (MOH) in Brazil. Method This was an observational, prospective, descriptive, and opinion-based study. The experts were in several Brazilian states. Twelve experts who fulfilled the inclusion criteria completed a questionnaire that explored their experiences and approaches to managing MOH in both the private and public sectors. Results According to most experts, more than 50% of migraine patients have MOH and psychiatric comorbidities. Experts abruptly stop pain medications, prescribing a bridge treatment for more than 50% of patients. Acute treatment is administered for up to two days per week. Prophylaxis was initiated immediately, and topiramate and monoclonal antibodies were the first choices, respectively, for 36.3% and 54% of professionals. The first follow-up appointment should occur within 4 weeks. Conclusions Further guidelines based on evidence as well as expert opinions should be developed for the Brazilian reality, and future prospective studies can be conducted to compare the effects of different treatment regimens for MOH.

Background Cervicogenic headache (CEH) is often refractory to monotherapies, and treatment strategies combining neuromodulation and myofascial interventions may offer additional benefits. This study evaluated the clinical effectiveness of ultrasound-guided C2 dorsal root ganglion (DRG) pulsed radiofrequency (PRF) combined with suboccipital myofascial plane block (SMPB) in subjects with CEH. Methods This retrospective study analyzed 67 CEH subjects treated with PRF alone ( n = 28) or combined PRF + SMPB therapy ( n = 39). Pain intensity (VAS), headache frequency and duration, Short-Form McGill Pain Questionnaire (SF-MPQ), and Neck Disability Index (NDI) were assessed at baseline, 1 week, 1 month, 3 months, and 6 months. Results The combined treatment produced significantly greater improvement in pain outcomes. At 3 months, VAS scores were 2.09 ± 1.38 in the PRF + SMPB group vs. 3.55 ± 1.11 in the PRF group (between-group difference Δ = −1.46; 95% CI −2.06 to −0.86; p < 0.001). Superior improvements were also observed in headache frequency, headache duration, SF-MPQ, and NDI at multiple timepoints. All subjects completed follow-up (attrition rate 0%), and no complications or minor adverse events were reported. Conclusions Ultrasound-guided C2 DRG PRF combined with SMPB demonstrated greater reductions in pain and disability than PRF alone in CEH. These findings provide preliminary, hypothesis-generating evidence supporting the feasibility and clinical utility of this multimodal approach. Prospective randomized trials with longer follow-up are warranted.

Chronic pain is an individual experience with physical and psychological dimensions. Ketamine is used in sub-anesthetic doses to treat chronic pain. We describe a proposed multidisciplinary approach with combined treatment of low-dose ketamine and pain-focused psychological and somatic therapies to benefit quality of life of disabled chronic pain patients. Beyond pain reduction, within the biopsychosocial approach, the treatment aims to achieve reduced suffering and improved pain management, functionality, and quality of life. Adopting a multidisciplinary approach can minimize exposure to ketamine and maintain a conservative ketamine dosing regimen. In this way, ketamine is not only used for the analgesic effects, but also to facilitate internal psychological processes of body-mind integration related to the pain identity and trauma. We illustrate the presented treatment approach with three cases of patients treated in a private clinic in Florida, United States. We describe the patients' original injury, ketamine and adjunct psychological and somatic therapies regimen, and short and longer-term outcomes from the patient's perspective. These results are preliminary, require replication with validated measures, and represent an opportunity for additional research and hypothesis formation. More clinical research on ketamine and adjunct therapies for chronic pain conditions is warranted to advance treatment options.

IntroductionWe present connectivity-based features associated with fibromyalgia, derived from raw EEG data at the sensor level.MethodsThese connectivity features were identified through a data-driven method, employing machine learning. We carried out some automatic, moderate pre-processing and extracted spectral connectivity features. Machine learning experiments then followed, employing feature importance analyses and feature selection techniques for building high-performing classification models; finally, based on robust cross-validation and test evaluation, we obtained the features associated with fibromyalgia. The raw EEG signals from 463 participants are used in the primary analysis. An external dataset that consists of 48 participants is used to validate the identified connectivity features.ResultsFive features in the gamma band (Fz-Cz, Pz-P4, Fz-C3, Cz-P4, and Cz-Pz) were able to objectively detect the presence or absence of fibromyalgia with an accuracy of 99.57%. The identified connectivity features associated with fibromyalgia also show promising results on EEGs that are collected using a different type of device.DiscussionEEG-based functional connectivity features associated with fibromyalgia, identified using machine learning in the gamma band at the sensor level, can distinguish between fibromyalgia participants and healthy controls with 99.57% accuracy. These findings advance our understanding of the brain-based mechanisms of fibromyalgia and provide novel targets for future non-invasive neuromodulation and neurofeedback trials. However, future studies need to replicate these findings in independent EEG datasets in people with fibromyalgia as well as compare with other clinical populations.