The Journal of Pain

BackgroundPersistent Spinal Pain Syndrome (PSPS) type II represents a challenging clinical entity with limited therapeutic options. Various spinal cord stimulation (SCS) modalities have emerged as potential treatments, but their comparative effectiveness remains unclear. ObjectiveOur goal in this paper is to systematically evaluate and compare the efficacy of different SCS modalities in patients with PSPS type II through meta-analysis of available randomized controlled trials. Evidence ReviewWe conducted a systematic review following PRISMA guidelines, searching major databases for randomized controlled trials evaluating SCS modalities in PSPS type II patients until the end of May 2025(search updated on October 3rd). Primary outcomes included pain intensity (VAS) and functional disability (ODI) at 6 and 12 months. Subgroup analyses compared tonic versus burst stimulation and high-frequency versus low-frequency SCS. FindingsNine randomized controlled trials were included, encompassing 565 patients across different SCS modalities. For the primary outcome of clinically meaningful pain relief ([&ge;]50% reduction), pooled analysis demonstrated that 45% (95% CI: 18-75%, I{superscript 2} = 92.2%) of patients achieved this threshold for back pain and 55% (95% CI: 45-65%, I{superscript 2} = 0%) for leg pain. Subgroup analysis revealed significant differences in back pain responder rates by stimulation modality: High-frequency SCS demonstrated responder rates of 92% (95% CI: 79-98%) versus 28% (95% CI: 13-49%) for conventional frequencies (p < 0.001). For leg pain, no significant difference was observed between tonic (51%, 95% CI: 37-65%) and burst stimulation (60%, 95% CI: 45-74%, p = 0.36) and mean VAS scores demonstrated significantly lower pain with high-frequency SCS (13.30, 95% CI: 8.82-17.78) compared to conventional frequency (28.42, 95% CI: 24.02-32.88, p<0.0001). For back pain, mean VAS scores decreased from a baseline of 73.03 to 41.67 (95% CI: 36.12-47.22, I{superscript 2}=22.8%) at 6 months and remained stable at 35.66 (95% CI: 25.39-45.93, I{superscript 2}=75.0%) at 12 months. Leg pain showed more pronounced improvement, with VAS scores declining from a baseline of 61.81 to 23.75 (95% CI: 17.69-29.81, I{superscript 2}=78.8%) at 6 months and 29.16 (95% CI: 24.81-33.52, I{superscript 2}=0%) at 12 months). Meta-regression identified longer pain duration and older age as positive predictors of response, while higher baseline leg pain predicted lower responder rates. Serious adverse events occurred in 10%, with a 16% revision surgery rate. Only two studies demonstrated a low risk of bias across all domains. ConclusionsCurrent evidence demonstrates that various SCS modalities provide clinically meaningful pain relief in PSPS type II patients, with approximately half achieving [&ge;]50% pain reduction. High-frequency SCS shows significantly superior responder rates for back pain compared to conventional tonic stimulation, while burst stimulation yields significantly superior reductions in continuous pain intensity metrics. However, the limited number of studies, substantial heterogeneity, and lack of head-to-head comparisons prevent definitive recommendations regarding optimal stimulation parameters. Future large-scale randomized trials with standardized protocols and responder-based outcomes are needed to establish evidence-based treatment algorithms for PSPS type II patients.

We performed the first systematic review and meta-analysis of the prevalence of pain with neuropathic characteristics using Bayesian methods to correct prevalence estimates for the use of screening tools with imperfect sensitivity and specificity (CRD42023416845). We searched major databases for national or regional epidemiological studies that reported the prevalence of pain with neuropathic characteristics, as identified by the PainDETECT, S-LANSS, or DN4-interview. Of the 1,251 unique records retrieved, 8 were finally extracted. The uncorrected (apparent) prevalence data were pooled using a random-effects meta-analysis for proportions. The corrected (true) prevalence was estimated using Bayesian models incorporating sensitivity and specificity distributions under non-informative [beta(1,1)] and informative priors [beta(4.389, 29.522); based on apparent prevalence]. Using the mean values from Bayesian credible intervals, a pooled estimate of true prevalence was generated using a random-effects model. The pooled estimate for the apparent prevalence was 10.6% (95% CI: 8.5; 12.9). The pooled estimate for true prevalence was 4.9% (95% CI: 3.8; 6.1) using informative priors, and 2.3% (95% CI: 1.5; 3.2) using non-informative priors. The use of imperfect screening tools may have overestimated the prevalence of neuropathic pain. PerspectiveThe prevalence of neuropathic pain may be lower than previously estimated. A lower prevalence should not be equated with reduced societal or clinical significance, but it may have implications for healthcare resource allocation and research funding policies for neuropathic pain.

Why some surgical participants experience pain that extends beyond the original site of injury while others do not remains poorly understood. Both pain intensity and widespread pain contribute to recovery and quality of life, yet their psychosocial correlates are often examined separately. Using data from two large pre-surgical cohorts--participants preparing for knee replacement or thoracic surgery--we examined associations between sociodemographic and psychosocial factors, pain intensity at surgical and non-surgical sites, and widespread chronic pain. Across cohorts and outcomes, fatigue showed the strongest and most consistent associations with pain intensity and widespread pain, independent of other measured factors. Fatigue also occupied a central position in statistical association networks and accounted for substantial shared variance among multiple psychosocial variables, including sleep disturbance, depression, stress, and socioeconomic disadvantage. Pain at non-surgical sites was strongly associated with widespread pain and frequently accounted for observed associations between surgical-site pain and widespread pain. Together, these findings highlight robust patterns of association linking fatigue, pain intensity, and widespread pain in pre-surgical populations. One Sentence SummaryFatigue is the strongest and most consistent factor linked to how pain intensifies and spreads before surgery.

New-onset chronic pain is a common and debilitating symptom of Long COVID (LC) that remains not fully understood in terms of pathophysiology and therapeutic targets. A growing body of evidence in chronic pain syndromes similar to LC demonstrates an association between EEG alpha oscillatory activity and the experience of pain, with clinical studies showing maladaptive changes in oscillatory activity, particularly a slowing of alpha activity. This study aims to investigate the association between EEG alpha oscillatory activity and pain perception in new-onset LC-chronic pain. We recruited 31 individuals (20 females) with a clinical diagnosis of LC reporting new-onset chronic pain and 31 healthy pain-free age-and sex-matched controls. Participants completed questionnaires regarding symptoms and psychological functioning prior to recording eyes-open resting-state EEG. Peak alpha frequency (PAF) and spectral power within the alpha band (8-13 Hz) were extracted from EEG signals. Lower PAF over the posterior scalp region was significantly associated with higher LC-chronic pain severity when controlling for age and depression. This observation was consistent across PAF estimation methods. PAF was significantly increased, particularly in the posterior region, in the moderate pain LC subgroup compared to both severe pain subgroup and controls, while alpha power did not differ between the three groups and was not associated with pain severity. Our findings highlight associations between PAF and pain symptoms in a new post-infection chronic pain syndrome. PAF can thus be explored as a potential biomarker and therapeutic target for EEG-based neuromodulation interventions in LC-chronic pain. These results may have implications for other similar chronic pain syndromes. SummaryLower resting-state EEG peak alpha frequency in posterior scalp region is associated with higher severity of new-onset Long COVID chronic pain.

BackgroundPatients understanding of pain and its biopsychosocial nature is thought to be important in order to optimize treatment decisions and treatment outcomes. A validated Spanish questionnaire for patients based on a biopsychosocial model assessing knowledge and attitudes of pain was unavailable. The aim of this study is to validate the Spanish version of the PACKA, to have a Spanish questionnaire to be used among pain patients in both clinical and research settings. MethodsPhase 1: forward and backward translation, and expert committee; Phase 2: a cross-sectional and longitudinal study among Fibromyalgia patients. In the cross-sectional study (n =330), internal consistency, structural validity and hypothesis testing were examined. ResultsThe 26-item PACKA was translated and validated in 4 stages. Acceptable internal consistency and test-retest reliability was demonstrated. Internal consistency: Cronbachs =0.776. Hypotheses testing: associations with the Neurophysiology of Pain Questionnaire r =0.31. ConclusionThis Spanish version of PACKA has shown acceptable validity and reliability in patients with Fibromyalgia. Further use and reanalysis of the questionnaire might improve this preliminary validation.

IntroductionChronic pain in fibromyalgia may be driven by abnormal ongoing activity in a subclass of C-fibre nociceptors known as Type1B or CMi nociceptors. As is common in C-nociceptor microneurography studies, the modest patient numbers in these prior studies generate large confidence intervals around the point estimate of the prevalence of this abnormal activity. This complicates the interpretation of the relative importance of this ongoing nociceptor activity as a pain generating mechanism in fibromyalgia. The study aims to improve precision via an adaptive Bayesian protocol that maximises the yield and quality of data collection whilst minimising patient burden. MethodsThe study employs an optimised microneurography protocol with an adaptive study design. The microneurography protocol incorporates early identification of CMi nociceptors via an abbreviated activity dependent slowing protocol to increase yields enabling efficient collection of the primary outcome data. The adaptive study design will use Bayesian principles to iteratively assess the predictive probability of futility, and terminate early if there is high confidence that the hypothesis is false. Furthermore, the study will employ questionnaires to explore links with pain in the area under study to the electrophysiology data. Finally, quantitative sensory testing will be used to investigate whether the irritable nociceptor phenotype is associated with abnormalities in CMi nociceptor physiology. Ethics & DisseminationThis study has received HRA REC approval in the UK. Participants will provide written informed consent, and may withdraw at any time without consequence. At the end of the study, the results will be disseminated through peer-reviewed publication, and the data made available via a data repository. Strengths & limitations of this studyBayesian predictive probability of futility to minimise patient burden in microneurography Microneurography for objective interrogation of the peripheral nervous system Optimised microneurography protocol to efficiently answer primary hypotheses Subjective elements of early termination criteria of the study assessed and co-developed with Patient and Public Inclusion and Engagement Group

BackgroundNeuropathic pain (NP) is a debilitating chronic pain condition caused by injury or disease of the somatosensory nervous system. Accumulating evidence indicates that astrocytes play a central role in neuroinflammatory regulation and synaptic remodeling, thereby critically influencing the initiation and persistence of neuropathic pain. However, a comprehensive overview of research trends and knowledge structures in this field is still lacking. MethodsThe analysis was conducted based on publications retrieved from the Web of Science Core Collection and Scopus, covering the period from 2000 to 2025. Studies focusing on astrocytes and neuropathic pain were systematically identified. Visualization and network analyses were performed using CiteSpace, VOSviewer, and the R package bibliometrix. Collaboration networks, co-citation patterns, keyword co-occurrence, and thematic evolution were analyzed to delineate research hotspots, developmental trajectories, and scholarly contributions across countries, institutions, authors, and journals. Results1,828 publications were included, showing a 15% average annual growth in output, which accelerated post-2010. The USA and China led in research and international collaboration, with studies concentrated in North American and East Asian institutions. Author productivity was uneven, with key researchers (Ji RR, Zhang Y, Watkins LR) contributing heavily to publications and citations. Pain and Molecular Pain were the core journals. Key themes included spinal astrocytic mechanisms, glial activation, and therapeutic modulation, with the focus evolving from injury models/markers to astrocytic activation and targeted pathways. ConclusionOur analysis shows a substantial growth in astrocyte-related NP research the past 25 years, underscoring astrocytes key role in chronic pain pathophysiology. Current trends underscore the integration of mechanistic insights with translational relevance, thereby informing future therapeutic and mechanistic advancements in NP.

BackgroundUnderstanding the associations among biopsychosocial factors is essential for improving research and treatment of chronic low back pain (CLBP). Here we characterized interrelations among biopsychosocial domains using network analysis and identified the most influential features in CLBP. MethodsData came from Quebec Low Back Pain Study, comprising 4,489 CLBP participants. We modeled relationships among baseline biopsychosocial features as networks, where nodes represent features and edges encode statistical or causal dependencies among them. Undirected network was inferred using distance correlation. Directed network was constructed using the Linear Non-Gaussian Acyclic Model, which estimates plausible causal directions. Influence maximization was performed using the Independent Cascade (IC) model to identify the most influential features in each network. ResultsIn the undirected network, physical function and pain interference were the most central nodes, followed by depression. In the directed network, fear of movement, catastrophizing, and widespread pain emerged as key downstream hubs receiving multiple causal inputs, whereas pain interference, physical function, and depression acted as major upstream drivers exerting broad causal influence. IC diffusion simulations further identified pain interference and physical function as the most influential features in the undirected and directed networks, respectively. ConclusionsPain interference, physical function, and depression consistently emerged as key components of the CLBP biopsychosocial network. These features exert causal effects on fear of movement, catastrophizing, and widespread pain, with diffusion analyses confirming their roles as system-wide drivers. Interventions targeting functionality and pain interference, rather than pain intensity alone, may yield broader benefits across psychological and functional domains.

BackgroundChronic pain affects 28 million UK adults. While physiotherapy and social prescribing are recognised as effective, evidence on integrating them remains limited. Digital biomarkers could objectively assess movement quality and pain physiology to support clinical decision-making. ObjectivesTo explore whether simple kinematic and electroencephalography (EEG) biomarkers can discriminate between correct versus incorrect exercise performance and high versus low pain states, and to consider how such tools might streamline social prescribing pathways for chronic pain. MethodsSecondary analyses of two open datasets: (1) KERAAL kinematic dataset: 900 recordings of trunk rotation exercises (21 participants) labelled "correct" or "incorrect" by physiotherapists; (2) EEG dataset: 145 resting-state recordings (100 individuals with chronic pain) categorised as high or low pain. Classification models (logistic regression, support vector machines, gradient boosting) were trained on extracted kinematic features (range of motion, smoothness, symmetry, jerk, coordination) and EEG features (frontal alpha asymmetry, connectivity, sample entropy, aperiodic exponents). Performance was assessed using accuracy, F1 score, AUC and calibration curves. ResultsKinematic classification achieved near-perfect performance: 100% accuracy and AUC = 1.00. Key features were shoulder abduction peak angle, symmetry index and jerk. EEG classification was strong: 93% accuracy, 0.97 AUC. Global theta and alpha connectivity, frontal alpha asymmetry and sample entropy were most informative. ConclusionAutomated kinematic and EEG markers can reliably differentiate correct exercise performance and current pain state. These digital biomarkers could inform physiotherapists and link workers when triaging patients into social prescribing programmes. Integrating digital assessment into social prescribing may reduce unnecessary appointments, enhance self-management and align care with the biopsychosocial model. Further studies should validate the approach in broader populations and examine implementation in real-world social prescribing services.

Two-pore domain potassium (K2P) channels are novel analgesic drug targets with existing in vitro and in vivo validation, however genetic associations in large scale populations have not been widely reported. By examining two comprehensive genetic databases (UK Biobank & FinnGen) and 136 pain-related traits, we highlight that multiple pain-associated signals are present within 500 kb of K2P gene transcripts, with particularly strong evidence for KCNK5 (TASK-2) and headache-related traits. This data benchmarks remarkably well against gene targets already considered to be well validated pain targets (voltage-gated sodium and transient receptor potential channels) and is enhanced when examining populations regularly consuming analgesics who also report pain. This data supports a rationale for developing therapeutic strategies to modulate K2P function in patient populations experiencing pain.

In this randomized, double-blind, controlled trial of 8 weeks of repetitive transcranial magnetic stimulation (rTMS) for chronic pain, we compared the classic primary motor cortex (M1) rTMS with a novel target-selection strategy based on pre-therapy cortical connectivity. Guided by principles of homeostatic plasticity, we tested whether stimulating the cortical site with the lowest pre-therapy global connectivity would be more effective than two active comparators: stimulating the site with the highest pre-therapy global connectivity or stimulating M1 independent of connectivity. Before starting rTMS treatment, TMS-evoked EEG potentials were recorded from four cortical targets: M1, the dorsolateral prefrontal cortex, the anterior cingulate cortex, and the posterosuperior insular cortex. For each target, global connectivity was quantified using a distance-weighted, phase-based index (debiased weighted phase lag index, wPLI) derived from pre- and post-TMS-evoked EEG activity, capturing both the magnitude and spatial extent of TMS-induced oscillatory phase locking across cortical regions. Target allocation in the Low- and High-Connectivity groups was based on this global connectivity measure. Ninety patients with chronic pain were randomized to Low-Connectivity, High-Connectivity, or Classic-M1 groups. Treatment consisted of 12 rTMS sessions delivered over 8 weeks to the assigned target. The primary outcome was the proportion of patients achieving [&ge;] 30% reduction in pain intensity. Secondary outcomes included continuous change in pain intensity, pain interference, sleep, fatigue, mood, quality of life, and patient global impression of change. No between-group differences were observed for primary or secondary outcomes (p > 0.05). In prespecified exploratory analyses, we examined whether pre-therapy local connectivity (within-target wPLI) predicted treatment response. In the Classic-M1 group, lower pre-therapy local M1 connectivity was associated with a greater reduction in pain intensity (r = 0.50, p = 0.005). This association was not observed in the Low- or High-Connectivity groups. A regression model including group-by-connectivity interaction indicated that the relationship between local connectivity and pain reduction differed between the Classic-M1 and High-Connectivity groups (p = 0.038). The results of this clinical trial showed that connectivity-based target allocation using global connectivity did not improve clinical outcomes. However, lower local M1 connectivity was associated with greater pain reduction following Classic-M1 stimulation, suggesting that local M1 connectivity may serve as a potential biomarker of response.

Acute pain in hospitalised patients is common and is associated with adverse outcomes, yet African data are scarce. We conducted an international prospective point-prevalence study of adult inpatients across Africa to determine pain prevalence and severity, and explored associations with critical illness and survival status. On a single day, investigators assessed patients worst pain in the preceding 24 hours using a 0-10 visual-numerical scale and recorded vital signs. Critical illness was defined as [&ge;]1 vital sign out of range, according to predefined definitions. Survival was assessed at day 7. Data are presented as median [IQR], n (%), and odds ratios with 95% confidence intervals. Between September and December 2023, 19438 patients from 180 hospitals in 22 African nations were included (age 40 [29; 59] years; 56% female). 67.9% of patients reported pain, with 2795 patients reporting severe pain (pain of [&ge;]7/10). Pain severity did not differ significantly by sex overall, but females [&le;]40 years old, with hypertension or cancer, admitted for trauma or infection, or in surgical wards had higher mean pain ranks than males. Severe pain odds decreased by 11% per standard deviation increase in age. Patients with severe pain had greater odds of critical illness and death within seven days. These findings provide the first large-scale evidence of acute pain burden in African hospitals. Pain is highly prevalent, with one in seven patients reporting severe pain. Future research of effective and feasible strategies to manage acute pain and reduce pain-related adverse clinical outcomes is needed in Africa.

Chronic pain (CP) is a multidimensional condition characterized by physical, emotional, and cognitive symptoms. However, many neuroimaging studies investigating the brain mechanisms of CP have focused on single-domain measures, most commonly pain intensity. Incorporating multidimensional symptom profiles may advance the understanding of CP, its neural underpinnings, and the development of clinically actionable biomarkers. Here, we aimed to empirically derive symptom dimensions of CP and relate them to resting-state brain activity and connectivity measured by electroencephalography (EEG). Using a data-driven approach, we identified latent symptom dimensions in 207 individuals with CP based on the brief, internationally validated PROMIS-29 profile, which assesses general health across key physical, mental, and social domains. Principal component analysis revealed two dimensions, affective burden and physical burden, closely corresponding to established PROMIS-derived health dimensions in other clinical populations. Resting-state EEG was obtained in a subsample of 116 participants using a mobile, rapid-to-deploy 29-channel dry-electrode system. Bayesian regression analyses provided moderate to strong evidence for a negative association between affective burden and beta-band connectivity, particularly in left frontal and somatomotor regions. Together, these findings demonstrate how empirically derived symptom dimensions captured by PROMIS-29 can be linked to scalable, network-level EEG biomarkers. This framework illustrates an EEG-informed strategy for biopsychosocial stratification in CP, with potential relevance for personalized symptom-targeted interventions.

Repetitive transcranial magnetic stimulation (rTMS) of non-motor cortical targets, including the left dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and posterosuperior insula (PSI), has been proposed as a treatment for chronic pain with variable clinical outcomes. Pre-treatment local cortical dynamics were hypothesized to serve as markers of chronic pain reduction. In this secondary analysis of a large clinical trial comparing different rTMS targets for pain relief, it was examined whether pre-treatment evoked cortical responses measured by electroencephalography after TMS of DLPFC, ACC, or PSI were associated with at least 30 percent reduction in pain intensity scored on a visual analogue scale. Forty-five patients with chronic pain received 12 sessions over eight weeks of 10 Hz rTMS to DLPFC, ACC or PSI. Cortical reactivity was quantified using global and local mean field power, and oscillatory dynamics were assessed using event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) in the alpha-band (8-12 Hz). Responders (20 of 45, 44%) compared with non-responders showed higher pre-treatment alpha-band ERSP and ITC over the stimulated cortical targets (both P<0.05), and higher alpha-band ERSP and ITC values were negatively correlated with the percentage change in pain intensity (both P < 0.05). These results suggest that elevated pre-treatment TMS-evoked alpha-band oscillatory activity may indicate a higher probability of pain reduction to non-motor rTMS in chronic pain. This supports the development of enrichment strategies using cortical neurophysiology-based markers in neuromodulation trials aimed at individualized, precision-oriented treatments.

PurposeThe purpose of this study was to analyze differences in physical therapy (PT) use among a nationally representative sample of adults with symptomatic arthritis according to the rurality of their residence. MethodsWe used data from the 2023 National Health Information Survey (adult sample) to identify individuals with symptomatic arthritis by using 2 survey items indicating whether a healthcare provider had diagnosed the participant with arthritis and whether the participant had experienced arthritis-related symptoms during the past 30 days. One survey item was used to identify whether the participant had participated in PT during the previous 12 months. Levels of rurality were defined, in ascending order, as "large central metropolitan," "large fringe metropolitan," "medium or small metropolitan," and "nonmetropolitan/rural," according to each participants county of residence. Univariate and multivariate statistics were used to determine the association of PT use with the level of rurality. National estimates were calculated using weighting variables. FindingsWe identified 5,749 adults (weighted = 40,358,683) meeting our definition of symptomatic arthritis. Compared to those living in large central metropolitan areas, participants living in medium or small metropolitan areas were 20% less likely to report PT use (weighted odds ratio: 0.80; 95% confidence interval: 0.66, 0.96) and those living in nonmetropolitan/rural areas were 30% less likely (weighted odds ratio: 0.70; 95% confidence interval: 0.56, 0.88). ConclusionsAmong adults with symptomatic arthritis, those living in more rural areas had lower odds of PT use than those living in less rural (more urban) areas.

Chronic pain is increasingly conceptualized within a stress-related framework. However, it remains unclear whether chronic pain and prototypical stress-related conditions--such as post-traumatic stress disorder (PTSD)--share common neurobiological substrates. To this end, we conducted a pre-registered transdiagnostic meta-analytic study of gray matter volume alterations in chronic pain (60 studies) and PTSD (20 studies). Disorder-specific meta-analyses revealed that chronic pain was associated with distributed volume reductions across ventromedial prefrontal, middle cingulate, and insular cortices, whereas PTSD exhibited a single cluster of reduced volume in the anterior cingulate/dorsomedial prefrontal cortices. A conjunction analysis revealed that both conditions converged onto an overlapping cluster of reduced volume in the bilateral medial orbitofrontal/anterior cingulate area. Using normative resting-state fMRI data (HCP 7T dataset), we found that chronic pain neuroanatomical abnormalities were embedded within a distributed architecture of large-scale circuits encompassing mesocorticolimbic/reward, default mode, salience, frontoparietal, dorsal attention, and somatosensory networks. On the other hand, the PTSD focal neuroanatomical alteration was embedded in a single large-scale circuit mapping onto the mesocorticolimbic/reward, default mode, salience, and visual networks. In both conditions, the mesocorticolimbic/reward circuit emerged as the most robustly involved large-scale network. Notably, the shared cluster of reduced volume showed functional integration within the mesocorticolimbic/reward and default mode networks, with neurochemical fingerprinting revealing robust spatial correspondence with dopaminergic, serotonergic, opioid, and endocannabinoid receptor/transporter maps. Overall, these findings suggest that chronic pain and PTSD, beyond disorder-specific alterations, converge on a shared large-scale network organization. The overlap between chronic pain and a prototypical stress-related disorder at the network level provides neurobiological support for conceptualizing chronic pain within a stress-related framework.

Sensory gating -- the brains ability to filter out repetitive sensory input -- is essential for preventing sensory overload. Impaired gating is frequently observed in nociplastic and other chronic overlapping pain conditions, yet the specific brain regions supporting this inhibitory process in humans remains unclear. Neuroimaging studies examining pain processing implicate the anterior insula (AI), posterior insula (PI), and anterior mid-cingulate cortex (aMCC), but their deeper locations limit direct mechanistic testing using conventional non-invasive techniques. Here, we leveraged low-intensity focused ultrasound (LIFU), a novel non-invasive neuromodulation method with high depth-penetration and millimeter resolution, to examine the contributions of the AI, PI, and aMCC to sensory gating of nociceptive stimuli. Twelve healthy adults completed four counterbalanced visits of a paired-pulse contact heat evoked potential (CHEP) paradigm while receiving LIFU targeted to each region or an active sham. Using surface electroencephalography (EEG), placed at site Cz, we quantified the peak-to-peak (P2P) amplitude of the cortical response to the first stimulus (S1), the second stimulus (S2), and used the ratio of the response to each stimulus (S2/S1 ratio) as an index of sensory gating. Subjective ratings of pain intensity to the second stimulus were also recorded. Results demonstrated that all subjects displayed sensory gating at baseline and thatLIFU produced region-specific effects. Both PI and aMCC neuromodulation reduced subjective pain ratings and significantly decreased S2 amplitude relative to sham, whereas LIFU to AI had no effect. Critically, only PI neuromodulation enhanced sensory gating by reducing the S2/S1 ratio. These findings identify the PI as a key contributor to gating of repetitive nociceptive input and a promising neuromodulation target for remediating sensory gating deficits in nociplastic pain.

BackgroundReverse total shoulder arthroplasty (rTSA) is an increasingly common surgical procedure often performed to treat pain related to glenohumeral osteoarthritis or to rotator cuff arthropathy. Although surgical outcomes are generally excellent, recent evidence has found that postoperative pain ([&ge;] 3/10) two years following surgery is reported by an estimated 18% of patients. Recently, the NIH Acute-to-Chronic Pain Signatures program recommended longitudinal studies using select biomarkers to describe and predict individual patient responses to surgery. These data are not yet available for rTSA procedures. MethodsThis was a longitudinal cohort study performed at a single academic medical center. Twenty participants undergoing rTSA surgery were included, recruited from a tertiary hospital system in the southern United States. The first objective of this study was to describe changes in general pain intensity (Numerical Pain Rating Scale), widespread body pain, anxiety (General Anxiety Disorder-7), depression (Patient Health Questionnaire-9), neuropathic pain symptoms (painDETECT), and quantitative sensory testing from baseline to 6 weeks following rTSA. The second objective was to identify the baseline demographic and pain-related factors associated with 6-week postsurgical improvements in pain intensity. ResultsFrom before to after surgery, our cohort demonstrated significant improvement in shoulder pain intensity, widespread body pain, PainDETECT score, and temporal summation magnitude measured at the surgical deltoid. Degree of 6-week pain intensity improvement was associated with baseline pain intensity (F=18.79, p=0.0004) and temporal summation magnitude of the tibialis anterior (F=5.06, p=0.0380). ConclusionsPain intensity, location, nature, and mechanism can serve as biomarkers of the short-term postsurgical changes that can be expected following rTSA. Baseline pain intensity and temporal summation magnitude of the tibialis anterior were associated with the degree of pain improvement, suggesting their use for preoperative risk assessment. Future research should evaluate whether these 6-week biomarker changes are associated with the development of chronic postoperative pain at longer durations after surgery. Level of EvidenceLevel I, Prognostic Study

There is evidence that adults with spinal cord injury (SCI) have deficits in mental body representations (e.g., altered visuospatial body maps and reduced body awareness), due to the diminished or lack of sensory information reaching the brain. These mental body representation deficits are important and need to be quantified, because they can impact daily functioning and they are associated with neuropathic pain. The currently available evaluation scales measure certain aspects of mental body representations with few having been assessed in adults with spinal cord injury. Furthermore, to our knowledge, no scales have been developed specifically for adults with spinal cord injury. Therefore, to address this gap, we completed two aims. First, we developed a novel evaluation scale (the SCI-BodyMap) to measure SCI-specific deficits in mental body representations. Second, we assessed the psychometric properties of inter-rater reliability, test-retest reliability, concurrent validity, with the Revised Body Awareness Rating Questionnaire, the Multidimensional Assessment of Interoceptive Awareness-2, and the Numeric pain rating scale. We also assessed feasibility, utility, and face validity with the QQ-10. We found good to excellent inter-rater and test-retest reliability, with the exception of two items showing moderate test-retest reliability. We did not find any correlations between the SCI-BodyMap with the Revised Body Awareness Rating Questionnaire or the Multidimensional Assessment of Interoceptive Awareness-2 and found fair correlations between high levels of neuropathic pain on the Numeric pain rating scale with highest level of neuropathic pain on the SCI-BodyMap. The scale proved to have high feasibility, utility, and face validity. Once more psychometric analyses are performed in a bigger sample, the SCI-BodyMap could be recommended for use in research and in the clinic.

IntroductionPatients undergoing anterior cruciate ligament (ACL) reconstruction experience substantial postoperative pain, which delays recovery and leads to both immediate and long-term opioid use. In other knee procedures, infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) has demonstrated analgesic and opioid reducing effects. However, the effect in patients undergoing ACL reconstruction has not been investigated. We aimed to investigate the real-world effect of IPACK in patients undergoing ACL reconstruction on immediate postoperative opioid consumption. ParticipantsIn this single-centre difference-in-differences cohort study, all patients who underwent ACL reconstruction surgery at Bispebjerg Hospital, Denmark, from 1 February 2024 to 30 June 2025 are included. The study further includes a similar reference cohort, comprising all patients who underwent trochleaplasty, Elmslie-Trillat, or medial patellofemoral ligament reconstruction during the same period, and at the same hospital. InterventionThe primary exposure is the implementation of IPACK as part of perioperative management for ACL reconstruction on 1 January 2025. The IPACK was performed under ultrasound guidance, immediately before surgery, administering 20 mL of ropivacaine 0.5% between the popliteal artery and the posterior knee capsule. OutcomesThe primary outcome is the cumulative opioid consumption from surgical incision to 2 hours postoperatively. Secondary outcomes include the cumulative opioid consumption from incision to 24 hours postoperatively, the worst reported pain score at 0-24h postoperatively, occurrence of postoperative nausea or vomiting (PONV) 0-24h postoperatively, length of PACU stay, length of hospital stay, and nerve injuries. As an exploratory outcome, carbon dioxide emissions will be investigated. Statistical analysisThe main analysis will be a standard two-way fixed effects DiD regression assessing the changes occurring at the time of implementation of IPACK in the ACL cohort, with adjustment for the underlying time trend. Continuous outcomes are reported as mean difference (95% confidence interval [CI]), and binary outcomes as absolute and relative risks (95% CI).