The Journal of Headache and Pain

Background: Light hypersensitivity, or photophobia, affects nearly 80% of people with migraine and is the most prevalent symptom after headache. Despite its high prevalence, the neural pathways underlying migraine-associated light hypersensitivity remain poorly understood, in part due to the lack of behavioral assays that directly assess light sensitivity in mice. Consequently, whether nociceptors contribute to the development of photophobia remains unclear. Methods: We established a novel light sensitivity assay (LSA) to quantify the response to light in mice by measuring facial grimacing. The assay was applied to evaluate light hypersensitivity elicited by three established migraine triggers: calcitonin gene-related peptide (CGRP), nitric oxide donor (sodium nitroprusside), and repeated stress. To determine the contribution of TRPV1 nociceptors, mice were treated with resiniferatoxin (RTX) to ablate these neurons. Results: The LSA detected light hypersensitivity following administration of CGRP, sodium nitroprusside, and repeated stress in wild-type (WT) mice. Sex differences were not observed in CGRP- or stress-induced light hypersensitivity. Furthermore, ablation of TRPV1 nociceptors did not reduce light hypersensitivity induced by migraine triggers. Conclusions: These findings present the LSA as a robust, reproducible, and easy to implement behavioral assay for measuring light sensitivity in preclinical migraine models. Our results further demonstrate that TRPV1 nociceptors are dispensable for the development of migraine-associated light hypersensitivity. This assay provides a useful method for investigating the mechanisms underlying light sensitivity and for evaluating potential therapeutic strategies.

Objective: To identify demographic and daily cognitive, affective, and contextual predictors of headache-related interference with activity and concentration in a smartphone-based migraine cohort, using statistical models appropriate to the ordinal structure of patient-reported interference. Background: Migraine burden extends beyond headache to encompass cognitive and affective disturbance, yet most disability instruments summarize functioning retrospectively and cannot capture day-to-day variability in interference. Ecological momentary assessment addresses this limitation, yet few studies have examined cognitive and affective correlates of interference independent of pain intensity or have modeled interference using methods that respect its ordinal, non-equal-interval structure. Methods: From May 2025 to April 2026, adult participants were enrolled in this prospective, decentralized observational study via specialty clinics and social media campaigns. Eligibility required fulfilling ICHD-3 diagnostic criteria for migraine using a validated electronic survey and experiencing between 3 and 20 monthly headache days. Enrolled individuals recorded daily smartphone diary entries and performed three brief cognitive tests over a 30-day monitoring period. Daily interference with activities and concentration were captured on 5-point ordinal scales and analyzed via cumulative link mixed-effects models incorporating participant-specific random intercepts. Predictor selection across nested specifications relied on likelihood ratio testing and Akaike Information Criterion (AIC) metrics, prioritizing the more parsimonious model when goodness-of-fit was comparable. Results: The analytic sample comprised 1,267 headache-day observations from 143 participants. In the final models, brain fog (OR = 2.49 for activity, 3.19 for concentration), forgetfulness (OR = 1.48, 1.65), and mood disturbance (OR = 1.19, 1.31) were each independently associated with both outcomes (all p < 0.01), while age, sex, and employment status showed no significant association with either. Sleep quality (OR = 0.86) and anticipated next-day enjoyment (OR = 0.81) provided additional explanatory value for activity interference (p < 0.05) but not for concentration interference, for which the three-predictor model of brain fog, forgetfulness, and mood alone was retained as the most parsimonious final model. Conclusions: Cognitive and affective symptoms, rather than demographic or socioeconomic characteristics, are the primary correlates of headache-related functional interference in this cohort. Activity and concentration interference are explained by partially distinct sets of daily influences, supporting the clinical value of assessing cognitive and affective symptoms alongside conventional pain-focused evaluation.

Background: Temporary 60-day percutaneous peripheral nerve stimulation (PNS) can relieve pain in refractory occipital neuralgia (ON), but whether it alters acute healthcare utilization relative to the natural trajectory of the disease is unknown, because prior studies have lacked a concurrent comparator. Methods: We performed a secondary analysis of prospectively collected data from a tertiary interventional pain center. Adults with medically refractory ON (primary diagnosis occipital neuralgia, ICD-10-CM M54.81) who underwent 60-day occipital PNS (n = 42) were compared with concurrent patients who were clinically eligible for PNS but were denied insurance authorization and continued optimized non-PNS management (usual care; n = 63). Headache-related emergency department (ED) encounters - index (occipital neuralgia) and non-index (other headache/facial-pain diagnoses) - were ascertained over the 12 months before and after the treatment window via the electronic record and the statewide health information exchange. Patients were 1:1 propensity-matched on a priori confounders (age, sex, baseline total headache-related ED utilization, HIT-6, and baseline headache-medication use). The primary analysis was a difference-in-differences (DiD) comparison of the change in headache-related ED utilization, reported as the additive difference (Hodges-Lehmann estimate, distribution-free 95% CI) and, alongside, as a multiplicative rate ratio (RR). Results: Thirty-six matched pairs were well balanced. Baseline headache-related ED utilization was nearly identical between matched groups (6.3 vs. 6.2 visits/year). Over the following year, PNS patients' utilization fell to 2.5 while usual-care patients' rose to 6.9. The DiD was 5.0 fewer headache-related ED visits per patient (95% CI 3.0-6.0; p < 0.001), corresponding to a rate ratio of 0.36 (95% CI 0.27-0.48; p < 0.001). Results were consistent in the full sample, in covariate-adjusted models, and after excluding controls denied for incomplete conservative-therapy trials. The effect was driven by non-index headache visits. Conclusions: Relative to a concurrent, matched usual-care cohort whose headache related ED utilization rose over time, 60-day occipital PNS was associated with a substantial reduction in acute-care use, strengthening the case for a role of PNS on healthcare utilization in refractory ON.

Trigeminal pain produces persistent facial hypersensitivity that is difficult to treat. Ion channels contribute to the pathology of trigeminal pain, but the consequences of their modulation remain poorly understood. We previously demonstrated that voltage-gated sodium channel Nav1.7 is a therapeutic target that can be indirectly modulated via interaction with collapsin mediated response protein 2 (CRMP2) to reduce membrane expression of Nav1.7 and trigeminal ganglion neuronal excitability. We used the Foramen Rotundum Inflammatory Constriction of the Trigeminal InfraOrbital Nerve (FRICT-ION) model of trigeminal neuropathic pain to characterize behavioral and supraspinal effects of indirectly modulating the peripheral CRMP2-Nav1.7 interaction via our novel Compound 194 (C194). FRICT-ION produced mechanical and cold allodynia, which were reduced by C194, but had no effect on non-evoked affective behaviors. Despite behavioral improvement, C194 did not normalize heightened glutamatergic activity in the parabrachial nucleus (PBN), revealing a dissociation between behavioral analgesia and activity of a central pain circuit. These findings extend mechanistic studies of C194 in the trigeminal system and demonstrate efficacy of CRMP2-Nav1.7 disruption in modulating facial pain-like behavior. These results support the CRMP2-Nav1.7 axis as a promising therapeutic target while highlighting the need to define how peripheral and central adaptations interact to shape persistent facial pain.

Background: Chronic musculoskeletal pain (CMP) is a common and debilitating symptom of Long COVID (LC), which shares several clinical features with Fibromyalgia Syndrome (FMS). Aims: This longitudinal study investigated whether the symptom overlap between LC-CMP and FMS persists over time, whether patterns differ according to pre-COVID CMP history, and the extent to which neuropathic pain features are present. Methods: Individuals with LC completed questionnaires assessing the symptom-based component of the 2010 American College of Rheumatology criteria for FMS and the presence of neuropathic pain features (PainDetect Questionnaire, PDQ) at baseline, 6- and 12-month follow-ups. Participants were grouped according to pre-COVID CMP history. Group differences were analysed using mixed-effects logistic regression. Results: 240 individuals completed the baseline assessment at a mean of 2.61 years after LC onset, including 131 (100 females) with new-onset CMP and 94 (87 females) with pre-existing CMP. The prevalence of participants meeting the symptom-based criteria for FMS remained high across follow-up (67.5-78.6%), with 50.0-61.0% of those with complete follow-up data fulfilling criteria at all timepoints. No significant subgroup differences were observed (OR = 0.43, 95% CI [0.14 1.39], p = 0.160). Across follow-up, 22.2-36.1% of participants reported likely neuropathic pain features, with significantly higher odds in the pre-existing CMP group (OR = 3.17, 95% CI [1.22 8.18], p = 0.017). Conclusions: FMS-like symptoms remain highly prevalent several years after acute COVID-19 and persist over a further 12 months, suggesting that LC-CMP frequently represents a persistent long-term condition with substantial overlap with FMS. These findings support closer integration of LC and chronic pain rehabilitation services and add to the wider literature linking post-infectious processes with FMS-like symptoms.

Neuropathic pain involves spinal microglial activation and metabolic changes.Forsythoside B (FB) has anti-inflammatory effects, but its role in neuropathic pain and microglial glycolysis remains unclear. We investigated the effects and mechanisms of FB in mice with chronic constriction injury (CCI) and in LPS-stimulated BV2 microglia.FB reduced mechanical allodynia and thermal hyperalgesia in CCI mice. FB also reduced the spinal levels of HIF-1, HK2, PKM2, LDHA, and CD86. It decreased the proportion of IBA1+/CD86+ cells and the levels of IL-1{beta}, IL-6, and TNF-. In LPS20 stimulated BV2 microglia, FB reduced glycolysis-related proteins, proinflammatory markers, and cytokine release. FB also reduced glycolytic activity and partly restored basal mitochondrial respiration. FB did not change Hif1a mRNA levels. However, it Manuscript Click here to access/download;Manuscript;Manuscript.docx increased HIF-1 ubiquitination and promoted its proteasome-dependent degradation. HIF-1 overexpression partly reversed the effects of FB on glycolytic enzymes, CD86 expression, and proinflammatory cytokine production. Immunoprecipitation followed by mass spectrometry and UbiBrowser analysis identified USP7 as a candidate HIF27 1-associated deubiquitinase. Molecular docking and cellular thermal shift assays supported a possible interaction between FB and USP7. FB reduced the association between USP7 and HIF-1. USP7 knockdown produced effects similar to those of FB on HIF-1 ubiquitination and downstream glycolytic and inflammatory responses.Overall, FB alleviated neuropathic pain and reduced proinflammatory microglial responses. These effects may involve the promotion of HIF-1 degradation through modulation of the USP7-HIF-1 regulatory axis.

Background and Objectives Transient ischemic attack (TIA) diagnosis is challenging because it relies mainly on clinical assessment and exclusion of common differential. Functional MRI (fMRI) may provide a diagnostic biomarker by detecting transient brain dysfunction not visible on conventional imaging. This pilot study aimed to characterize acute motor-task BOLD activation in patients with suspected DWI-negative TIA and compare functional patterns between confirmed TIA and alternative diagnoses. Secondary objectives were to assess longitudinal changes in activation and connectivity at 3 months. Methods In this prospective single-center study, adults presenting within 24 h of transient anterior-circulation neurological symptoms underwent conventional MRI and additional motor-task fMRI. Patients with acute DWI lesions were excluded. Final diagnosis was established after 3-month follow-up. Whole-brain analyses, individualized motor cortex region-of-interest (ROI) analyses, and generalized psychophysiological interaction (gPPI) connectivity analyses were performed during the acute phase and at 3 months. Results Eight patients were enrolled; six had complete longitudinal imaging data and were included in the final analyses. Final diagnoses were TIA (n=2), migraine aura (n=2), functional neurological disorder (n=1), and hypoglycemia (n=1). Whole-brain and ROI analyses showed reduced bilateral motor-related BOLD responses during the acute phase in both TIA patients and in the patient with hypoglycemia. In contrast, patients with migraine and functional neurological disorder exhibited less marked longitudinal changes. In TIA patients, motor cortex activation increased at 3 months, tending to normalize toward values observed in non-TIA participants. Connectivity analyses revealed heterogeneous patterns, but the 2 TIA patients demonstrated increased longitudinal connectivity between the motor cortex contralateral to symptoms and other sensorimotor regions, including supplementary motor, premotor, parietal, and postcentral cortices. Discussion These preliminary findings suggest that TIA may be associated with transient bilateral reductions in motor-network activity. Functional abnormalities appeared to improve over time, supporting the hypothesis of reversible network dysfunction. Although limited by the very small sample size, this study provides the first longitudinal assessment of emergency task-based fMRI in rigorously defined TIA and supports further investigation of acute functional MRI as a potential biomarker of transient cerebral dysfunction.

While progress has been made in identifying pain biomarkers using neuroimaging, the development of reliable EEG-based biomarkers remains challenging, limited by small sample sizes and the lack of adequate control conditions. We present a comprehensive dataset from 125 pain-free adults, comprising electroencephalogram (EEG) recordings, and behavioural, sociodemographic, and psychological data. Galvanic skin response and electrocardiogram data were also recorded in a subset of participants (n = 76). Participants received two sustained painful stimulations (thermal, chemical) and two sustained aversive non-painful stimulations (auditory, taste), each delivered twice (with and without continuous intensity ratings). Data are provided in Brain Imaging Data Structure format, where all physiological, stimulus-related, and behavioural data are synchronized within the EEG data files for easy access and analysis. Technical validation confirmed data integrity, with spectral and physiological analyses showing responses associated with stimulus intensity and subjective pain/unpleasantness levels. By providing multimodal physiological data across painful and non-painful aversive conditions, this initiative represents a valuable resource for developing or validating biomarkers and exploring the multidimensional nature of pain perception.

Pain is associated with dynamic brain reorganization. Electroencephalographic microstates can characterize transient large-scale brain states, yet findings across pain studies are inconsistent. Two features may contribute: conditions have been studied in isolation, and analytical pipelines vary widely. We applied a harmonized analysis pipeline across three pain conditions: capsaicininduced pain, assessed within participants against a pain-free baseline, and non-chronic and chronic back pain, each compared with matched controls. Using a five-minute resting-state electroencephalographic recordings we examined microstate topography, temporal expression and transition probabilities, and directly compared pain related differences across pain states. We identified five microstates (A-E), corresponding to auditory, visual, salience, and attentional networks. Capsaicin pain showed increased expression of microstate C and reduced expression of microstates A, D and E. Transitions were redistributed towards microstate C, indicating a shift toward salience-related processing at the expense of sensory and attentional dynamics. In clinical back pain, effects were smaller and diverged by pain type: non-chronic back pain showed lower microstate C occurrence, opposite in direction to the capsaicin effect, whereas chronic back pain showed lower microstate D global explained variance, suggesting salience and attentional differences in clinical pain. Direct comparisons showed weaker pain-related increases in microstate C expression in both clinical back pain groups than capsaicin pain, with additional differences involving microstates A, D and E. These findings argue against a unitary EEG microstate signature of pain and instead reveal pain-type-specific patterns of large-scale brain dynamics, with microstate C providing the clearest distinction between experimental and clinical pain.

Background: Cervical spinal cord (CSC) compression and myelopathy are frequent, severe complications in mucopolysaccharidosis (MPS) types I and VI. Early detection is critical to prevent irreversible neurological deficits and preserve quality of life. This prospective study aimed to identify quantitative neuroimaging biomarkers of structural CSC damage and myelopathy in MPS I and VI. Methods: Structural and diffusion magnetic resonance imaging (MRI) of the CSC was analyzed in 17 MPS I patients, 3 MPS VI patients (19{+/-}7 years), and 19 case-matched healthy controls (20{+/-}7 years). CSC macrostructure (cross-sectional area, diameters) and microstructure (fractional anisotropy [FA], radial [RD], mean, axial diffusivities) were evaluated within and beyond the maximal compression areas. Results: MPS patients demonstrated reduced CSC cross-sectional area and anterior-posterior diameter at upper cervical levels, alongside widespread microstructural alterations (lower FA, higher RD) throughout the CSC versus controls (pFDR<0.05). Restricted foramen magnum space was associated with microstructural damage at lower cervical levels without overt macrostructural compression. Morphological and microstructural metrics were sensitive to CSC compression and myelopathy severity (pFDR<0.05). Lower CSC integrity correlated with more advanced growth retardation (p<0.001). Among patients receiving hematopoietic stem cell transplantation, earlier treatment correlated with preserved upper CSC morphology (p<0.05). Distinct neuroimaging phenotypes were observed across MPS genotypes (pFDR<0.05). Conclusions: CSC MRI provides candidate neuroimaging biomarkers for early detection and characterization of myelopathy in MPS I and VI. Structural damage extends beyond primary maximal compression areas, highlighting these markers for clinical monitoring and future therapeutic trials.

Background: Although opioids are frequently prescribed for refractory chronic neuropathic pain, few data are available on baseline factors that may identify individuals more likely to respond and inform individually tailored practice. Methods: This was a post hoc, exploratory analysis of individual-level data from a placebo-controlled trial of methadone for chronic neuropathic pain (NCT05235191). Baseline clinical, psychological, psychophysical and radiological variables were tested for association with 30% or more pain reduction in the methadone group. The correlation between expectation of improvement and pain reduction was examined in both groups. Results: Of the 81 participants completing the 8-week follow-up, 28 (70%) on methadone and 14 (34.1%) on placebo achieved 30% or more pain reduction. In the methadone group, responders had higher baseline expectation of improvement (median 100 [80-100] vs. 55 [50-81]; p=0.004), which correlated moderately with percentage pain reduction (rs=0.508; p<0.001). Neither finding was observed in the placebo group (p=0.211 and p=0.161, respectively), although the correlation did not differ significantly between groups (p for interaction=0.728). Other clinical, sociodemographic, psychological and psychophysical variables were not associated with response. In the subsample with peripheral neuropathic pain and structural MRI (n=37), lower left precentral cortex volume was associated with response to methadone (p=0.041), and lower right paracentral volume with response to placebo (p=0.003). Conclusions: Baseline expectation may influence treatment outcomes, supporting its inclusion as a covariate to improve the precision of treatment effect estimates in trials, and its use in clinical practice to help tailor treatment to individual patients. These exploratory findings require confirmation in larger studies.

Introduction: Observation of a partner in pain elicits empathy-related cortical responses and social support can modulate pain. Objective: The aim of this study was to investigate empathy and the cortical response during observation of a romantic partner in pain with and without consoling touch. Methods: A total of 40 participants (20 couples) completed validated measures of handedness, pain and empathy. Each member of the couple was randomly assigned to be either the recipient of cold pressor pain or the consoling partner undergoing EEG. EEG activity was recorded from the consoling partner during baseline and pain conditions (with and without consoling touch) to investigate how observation of a partner in pain could alter mu rhythms. Results: Observing a romantic partner in pain significantly enhanced mu at electrodes C4 and Cz, yet addition of consoling touch did not significantly change mu rhythms. Personal Distress was positively associated with mu rhythm enhancement at electrode C4 during pain without consoling touch (r = .576, p = .008). Conclusion: Viewing a romantic partner in pain significantly increased mu rhythms, that was not further changed by offering consoling touch. The association between increases in mu rhythms and Personal Distress in the current study suggests that self-oriented distress may be especially relevant to sensorimotor cortex responses when witnessing a partner in pain, particularly when consoling touch is not possible. Keywords: pain; empathy, EEG, mu rhythms, cold pressor

Introduction: Neuroinflammation is a known pathophysiologic mechanism in multiple sclerosis and a proposed mechanism in fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Positron Emission Tomography (PET) imaging of the translocator protein (TSPO) has been widely used to measure neuroinflammation, though second-generation ligands are highly sensitive to a single nucleotide polymorphism, rs6971, resulting in high, mixed, and low affinity binders. It is unknown whether this polymorphism is associated with neuroinflammatory disorders. Materials and Methods: Eighty-six total participant genotypes for TSPO binding affinity were identified through Sanger sequencing (30 fibromyalgia, 21 ME/CFS, 11 multiple sclerosis, and 24 healthy controls). Associations between patient group and genotype were assessed with Fishers Exact test. Associations between genotype and symptom severity from self-report questionnaires were assessed with Kruskal-Wallis tests. Results: In the present study individuals with fibromyalgia, (ME/CFS), or multiple sclerosis were more likely to have a mixed- or low-affinity genotypes compared to healthy controls. Presence of the low or mixed genotypes were also associated with greater self-reported fatigue severity and depressive symptoms. Discussion: These findings should be confirmed in larger samples but suggest functional consequences of rs6971 polymorphism that may be related to the pathophysiology of pain and fatigue illnesses.

Despite urgent need for better analgesics, drug development has been complicated by incomplete bench-to-bedside translation. A likely contributing factor is the poor connection between the experimenter-evoked pain-related measures often used in preclinical models, and the clinical symptoms, like broader functional impairment, reported by patients. Here, we asked whether vertical climbing, a species-specific elective behaviour in mice, could serve as a measure of pain-related impairment. We tested male and female mice in a wide range of pain-related models including models of post-operative pain, inflammatory injury, osteoarthritis, rheumatoid arthritis, cancer-induced bone pain, fibrous dysplasia, neuropathic pain, migraine-related pain and facial neuropathy. Vertical climbing was reduced in all models, across five different laboratories, demonstrating the robustness and consistency of this type of behaviour as a novel pain-related outcome measure. Reduced climbing correlated significantly with established pain-related measures, but its time course diverged from that of evoked mechanical allodynia, while aligned more closely with other non-evoked behaviours, like burrowing, home cage activity, wheel running or weight bearing. Pharmacological validation was bidirectional: gabapentin restored climbing in mice with neuropathic injury, and naltrexone reinstated the climbing deficit in mice that had recovered from intraplantar CFA, consistent with persistent pain held in remission by endogenous opioid signalling. Overall, our results indicate that voluntary vertical climbing is a stable, elective behaviour that provides a robust and translationally relevant measure of pain-related functional impairment in mice.

Introduction Low back pain (LBP) is a common leading cause of functional disability in adults worldwide, presenting with Modic changes that are visible within the endplates of the vertebral body under magnetic resonance imaging (MRI). Modic changes (MC) are not just a coincidental imaging finding; they reflect underlying pathology that needs treatment focus. This study aimed to ascertain the prevalence and patterns of Modic changes in the lumbar spine among adult patients with a history of low back pain attending the Kilimanjaro Christian Medical Centre (KCMC) Orthopedic clinic. Methods A descriptive cross-sectional study was conducted at the KCMC orthopedic clinic from 2nd October 2024 to 30th May 2025. Data from adult patients with a history of low back pain who had undergone lumbar spine MRI were collected, cleaned, and analyzed in SPSS (version 25). Categorical variables were summarized by frequency and proportion, while continuous variables were summarized using the mean and standard deviation. Frequency tables, histograms, and pie charts were used for results presentation. Results Of the 283 patients enrolled in the study, the mean age was (57.2 {+/-}15.7) years, with the majority (145; 51.2%) being aged > 59 years. Most patients, 203 (71.7%), were females, while 176 (62.2%) were married, and 142 (50.2%) were overweight. The prevalence of MC on the lumbar spine among patients with a history of low back pain was 66.4% (n=188). Among patients with lumbar spine MC, the majority, 112 (59.6%), were aged over 59 years, and 125 (66.5%) had lumbar spine MC type II, which was the most predominant compared to other types of MC. Conclusion Modic changes on the lumbar spine are prevalent in adult patients with low back pain, particularly those over 59 years, with type II being the most common. Healthcare professionals and policymakers should recognize Modic changes as clinically relevant findings that require consideration in the management of patients with a history of low back pain rather than dismissing them as mere incidental or coincidental observations.

The genetic evidence for an essential role of sodium channel Nav1.7 in human pain conditions is compelling. Unfortunately, potent selective channel blockers of Nav1.7 are not useful analgesics because they have deleterious side effects, particularly on the autonomic nervous system. Here we have evaluated the downstream mechanisms induced by Nav1.7 loss in utero. Nav1.1 compensates for loss of Nav1.7 in sensory neurons and antisense Nav1.1 oligonucleotides diminish excitability in Nav1.7 embryonic null sensory neurons. Enhanced endogenous opioid signalling contributes substantially to analgesia. This is linked to altered gene expression that potentiates opioid signalling through lowered levels of proteins that terminate G-protein signalling (RGS4 and RGS8). There is also enhanced opioid drive through increased enkephalin levels linked to lowered sodium levels in Nav1.7 null neurons. Opioid signalling is the main driver of analgesia, but enhanced potassium channel expression (KCNC4 KCNK2, KCNMB2, KCNAB3) all implicated in pain control, may also contribute to the small level of naloxone-resistant analgesia. These findings suggest a potential new route to analgesia, through mimicking the events at Nav1.7 null sensory neuron terminals. Here we demonstrate potentiation of suzetrigine-evoked analgesia with RGS antagonists alone or in combination with normally inactive doses of morphine in formalin-evoked pain and CFA-induced inflammatory pain. Intriguingly, no analgesia is observed with acute pain. Cancer pain is under investigation. These data are of potential clinical interest.

Purpose: The aims of this study were to develop an externally validated deep learning vascular segmentation model for digital enhancement of vertebral artery dissection detection on CTA and to assess clinical utility of the model through a paired crossover reader study. Materials and Methods: This retrospective, IRB-approved study conducted from September 2024 to July 2026 included an internal training cohort of 84 manually segmented CTAs plus 17 CTAs from the RSNA Intracranial Aneurysm Challenge (101 CTAs total) and an external testing cohort of 40 CTAs (22 positive, 18 negative for vertebral artery dissection). A nnU-Net (version 2) model was trained using five-fold cross-validation with the entire training cohort. Technical performance was evaluated using the Dice similarity coefficient (DSC). A two-part crossover reader study included 10 readers who assessed diagnostic accuracy, confidence, and interpretation time with and without segmentation-based augmentation. Statistical analyses included McNemar's exact test (accuracy) and Wilcoxon signed-rank test (confidence, time), with P < .05 considered significant. Results: The model achieved a DSC of 0.96 (SD 0.01). In the reader study, diagnostic accuracy was lower with augmentation than without (0.72 vs 0.84, P < 0.001), while confidence (3.98 vs 3.96, P = .77) and interpretation time (137.3 vs 166.7 seconds, P = .54) did not differ significantly. Subjectively, 7 of 10 readers reported they would use the tool routinely in acute or trauma settings. Conclusion: Although the deep learning model demonstrated accurate segmentation of vascular structures, further validation is needed to establish its utility for enabling accurate diagnosis of VAD in fast-paced clinical settings.

Interoception is described as the sensitivity to internal bodily stimuli, and plays an important role in pain perception. Heightened interoceptive sensibility (i.e. self-reported interoceptive abilities) may reinforce misinterpretation of stimuli, enhancing pain perception. This study aimed to investigate the relationship between interoceptive sensibility and acute postoperative pain. Interoceptive sensibility was measured using the Private Body Consciousness Scale in two prospective observational surgical cohorts: a Caesarean delivery cohort (C-section cohort) of 146 patients, and a lower extremity orthopaedic surgery cohort (Ortho cohort) of 70 patients. One day after surgery, patients rated pain (primary outcome) and other postoperative symptoms (secondary outcomes) on a 0-10 scale. Bonferroni corrections were applied to secondary outcomes. Interoception positively correlated with pain (C-section cohort: Spearmans rho = 0.182, P = 0.028; Ortho cohort: rho = 0.259, P = 0.031), and with dizziness (C-section cohort: rho = 0.309, P = 0.002; Ortho cohort: rho = 0.348 P = 0.041) in both cohorts. In the C-section cohort, interoception correlated with shivering (rho = 0.321, P < 0.001). In the Ortho cohort, interoception correlated with nausea (rho = 0.366, P = 0.023) and helplessness (rho = 0.363, P = 0.026); whereas no correlation with pain catastrophising was found (rho = 0.240, P = 0.539). In pooled multiple linear regression analysis (n = 216), interoception predicted pain after controlling for age, sex and anaesthetic technique (B = 0.119, 95% CI [0.027-0.210], P = 0.011). These findings highlight the potential role of interoception in identifying patients at risk for acute postsurgical pain.

Background: Pressure pain threshold (PPT) is commonly assessed using pressure algometry. Self-administered algometry could reduce examiner involvement and may facilitate repeated assessment outside specialist settings. Objective: To examine the concurrent agreement of a previously described syringe-based pneumatic algometer with a commercially available comparator during self-administered PPT measurement in healthy adults. Methods: Thirty healthy volunteers completed researcher-administered and self-administered pain threshold measurements utilizing an AMF-500 device and the syringe-based pneumatic algometer. Results: During self-administration, measurements from the two devices were strongly correlated (r = 0.82, p < 0.05); the mean paired difference was 6.01 N (95% CI, -0.58 to 12.59 N). Self-administered test values were lower than researcher-administered test values in the fixed-order comparison (p = 0.0029). Conclusion: According to our findings the proposed device is a valid tool for autoalgometry and may potentially be introduced as an element of routine self-assessment of PPT.

Approximately 1 in 4 women with chronic pelvic pain (CPP) report persistent pelvic pain after hysterectomy. Centralized symptoms-fatigue, multisite pain, and sleep disturbance, quantified using the Fibromyalgia Survey Score (FSS)-often co-occur with this risk, but the trajectory of centralized symptom burden after surgery, independent of pelvic pain outcome, is not well understood. Whether presurgical differences in central nervous system pain processing distinguish women whose centralized symptoms improve (improvers) from those whose do not (non-improvers) has not been tested. In this observational study, we assessed whether individuals who do and do not report improvement in FSS scores six months post-operatively differ in their baseline/pre-operative phenotypes and brain function. Sensory sensitivity scores were significantly higher in non-improvers than in improvers at baseline. We identified no significant, presurgical differences in age, average pelvic pain intensity, widespread pain, or pain interference between improvers and non-improvers. Functional connectivity was examined at rest and during the application of a distal, sustained pressure pain. We identified no significant group differences at rest. During sustained pressure pain, non-improvers showed greater connectivity than improvers between primary somatosensory cortex and posterior thalamic seeds with frontal, motor, cerebellar and limbic regions, but lower connectivity between the periaqueductal gray and subgenual cingulate cortex. Non-improvers also showed a greater pain-evoked increase in connectivity between the pelvic and leg representations of the primary sensory cortex and other sensorimotor regions in the pain-versus-rest contrast. Overall, non-improvers showed increased functional connectivity between regions associated with the multisensory integration of ascending pain, and decreased connectivity between regions associated with descending pain modulation. In exploratory analyses, some of these connections were additionally associated with symptom burden: sensory sensitivity, number of painful regions, and pain interference. This work may inform mechanisms of persistent symptom burden and guide surgical decision-making in patients with high central sensitization.