European Journal of Pain

Although the biopsychosocial model of chronic pain is widely recognized, few studies include social-societal factors. Here, we examined how these interact with psychological factors to shape pain outcomes. We collected self-reported data from 262 participants with chronic pain about emotional states, pain coping strategies, social interactions, societal stressors and pain outcomes. After replicating previous partial correlation networks including only psychological factors, we extended our analysis to include social and societal factors, which demonstrated that these had strong direct relationships with quality of life and were indirectly related to pain intensity and pain disability. Our results indicate that social and societal factors are important for understanding pain outcomes and should be considered in interventions targeting chronic pain. Future work should examine the interactions among social-societal and psychological factors in more depth to inform ways to incorporate this into individual pain management and societal interventions for chronic pain.

Patients suffering from chronic pain are known to exhibit distinctive personality traits and impaired neuropsychological performance across various cognitive domains. However, there is currently a lack of comprehensive evidence regarding cognitive and behavioral functioning patterns in patients with trigeminal neuralgia. In this study, we aimed to thoroughly characterize a range of psychological and neuropsychological variables in a sample of 80 patients and 34 healthy controls, and to assess their relationship with pain intensity and duration. Our findings revealed that patients with trigeminal pain scored significantly higher on measures of anxiety, depression, perceived stress, alexithymia, pain catastrophizing, harm avoidance and lower on Self-transcendence subscale compared to healthy controls. Additionally, these patients demonstrated lower performance scores on tasks assessing working memory and verbal fluency. These findings may provide valuable insights for the development of personalized treatment plans for patients with trigeminal neuralgia, specifically targeting their unique personality traits and cognitive impairments.

BackgroundAlthough benign most of the time, neck pain (NP) has been observed as the early manifestation of various serious cervical pathologies (e.g., malignancies, fractures). Red flags (RF) are signs and symptoms that raise suspicion of serious spinal pathology. Considering that it has been estimated that the incidence of delayed diagnosis of serious cervical pathologies ranges from 5% to 20%, investigating RFs for NP remains a priority for an informed practice and the patients safety. Therefore, the following systematic review will aim to identify red flags recommendations to triage serious pathologies in current clinical practice guidelines (CPGs) for patients with NP, to evaluate the consistency between different CPGs regarding RF recommendations, and to investigate on what study type the recommendation of CPGs are based. Material and methodsWe will search for CPGs for patients with specific or non - specific NP by searching MEDLINE (via PubMed), EMBASE, and PEDro electronic databases. Guidelines will also be searched through forward and backward citation tracking strategies (Web of Science), by consulting experts in the field, and by checking guideline organization databases. Also, we will screen the references of two recently published systematic reviews on CPGs for NP. For all the CPGs included, we will extract bibliographic information, the serious pathologies considered, the RF considered for all serious pathologies, the reference used to support all the RF cited in the guideline, and, if available, the diagnostic accuracy data for all the RF. Two authors will independently perform the study selection and data extraction processes. Data synthesisResults will be presented descriptively and using graphs and tables. We will evaluate the consistency among the guidelines in their endorsement of red flags using Fleiss kappa. Fleiss kappa will be presented separately for all serious pathologies the CPGs consider.

ImportancePain is inherently aversive but provides emotional relief for individuals engaging in non-suicidal self-injury (NSSI). Despite the high prevalence and severity of NSSI, the neural mechanisms underlying pain processing in individuals with NSSI remain poorly understood. ObjectiveTo compare brain structure and functional connectivity between individuals with NSSI and controls and to relate brain function to pain inhibition. DesignCross-sectional, experimental. SettingMR Center at the Karolinska University Hospital in Stockholm, Sweden. ParticipantsWomen aged 18-35 years with NSSI (n=41) or matched healthy controls (n=40). ExposuresEngagment in self-injury [≥] 5 days during the last year. Main outcomes and measuresMagnetic Resonance Imaging (MRI) was used to examine brain structure and function related to pain regulation in individuals with NSSI (n=41) and healthy controls (n=40). The experimental pain test Conditioned Pain Modulation (CPM) was used to determine descending pain inhibition. ResultsWe found higher connectivity between the brains somatomotor networks and subcortical areas during resting-state functional MRI in NSSI compared to controls (P=.009; Bonferroni corrected), particularly involving the thalamus and caudate nucleus. The connectivity was linked to the level of descending pain inhibition during CPM. There was no difference between NSSI and controls regarding brain morphometry. Conclusions and relevanceOur findings suggest that individuals with NSSI may rely more on sensory-motor activations to regulate emotions. This study provides the first evidence linking specific brain circuits to pain regulation and self-injury behavior, highlighting potential pathways for more effective treatments for NSSI and related mental health conditions.

Background. Lifetime exposure to trauma is associated with chronic pain. Separate studies of chronic pain and trauma report overlapping alterations in white matter microstructure, yet their distinct and cumulative effects remain unclear. Methods. White matter microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) from the UK Biobank (N = 21,995) were analysed using linear mixed-effects models. First, group effects (chronic pain versus control) on white matter integrity within this cohort were established. To investigate distinct and cumulative impacts of trauma exposure at different developmental stages, main and interactive effects of group and trauma severity on FA and MD were examined in separate groups exposed to childhood maltreatment only, adulthood trauma only, and both. Sex-stratified analyses were conducted. Results. Chronic pain was associated with widespread alterations and was spatially refined to brainstem tracts and cingulum when accounting for maltreatment/trauma severity. Accounting for chronic pain, cumulative trauma severity was associated with alterations in brainstem, frontal and parietal tracts, whereas adulthood trauma showed comparable but attenuated patterns. Childhood maltreatment severity was associated with localised FA and MD reductions in brainstem tracts, sagittal stratum and superior longitudinal fasciculus. These effects were more pronounced in females than males. A chronic pain-by-maltreatment/trauma severity interaction was observed for FA in the superior cerebellar peduncle in females exposed to childhood maltreatment only. Conclusions. Distinct and interactive effects of chronic pain and maltreatment/trauma severity on white matter microstructure were evident. The findings suggest that trauma-informed care should be tailored by timing of exposure and sex in this population.

BackgroundPeople with malignant (primary or metastatic) or benign tumors may present in clinical practice with neck pain, with or without other symptoms (e.g., radicular pain or headache). When not presenting as an emergency, neck pain is most often assessed by primary care clinicians such as general practitioners, physiotherapists, chiropractors or osteopaths. Therefore, primary care clinicians must be able to screen for tumors when evaluating patients with neck pain. Despite clinical practice guidelines providing recommendations to triage serious conditions presenting as neck pain, there is a paucity of overviews on red flags for tumors in patients presenting with neck pain in primary care settings. The present scoping review aims to comprehensively map the existing literature on red flags for tumors in patients presenting with neck pain in primary care settings. Furthermore, we will aim to identify gaps in the literature to direct future research in this area. MethodsWe will search MEDLINE (via PubMed), Embase, CINHAL, and Scopus. In addition, we will use Web of Science to implement backward and forward citation tracking strategies. We will consider any primary study design written in English or Italian. No time or geographical restrictions will be applied to the search. Studies with a focus on the diagnostic pathway, considering patients of any age and gender with a diagnosis of tumor and a primary complaint of neck pain will be eligible for inclusion. Only studies conducted in primary care settings will be considered. Two authors will independently perform the study selection and data extraction phases. Results from the scoping review will be summarized descriptively through tables and diagrams. As a scoping review, we will highlight any gaps in the existing literature regarding our research questions.

BackgroundPeople with chronic pain report feelings of uncertainty and unpredictability around their future pain. A pain-forecasting model could provide important information to support individuals to manage their daily pain and improve their quality of life. To be useful, the model should be developed with people living with chronic pain. We conducted Patient and Public Involvement (PPI) work, with the aim of this PPI to design the content of a pain-forecasting model by (1) learning participants priorities in the features of pain provided by a pain forecast and (2) understanding the benefits that participants perceive they would gain from such a forecast. MethodsA focus group of 12 participants identified potential features, benefits and drawbacks of a pain forecast. In a survey, participants with chronic pain (n = 148) prioritised the identified pain features and perceived benefits. ResultsFocus group participants identified anticipatory anxiety and fears around data-sharing as potential drawbacks. Survey respondents prioritised forecasting of pain flares (68%) and fluctuations in pain severity (64%). Specific priorities about pain flares were the timing of the onset and the severity. Of those surveyed, 75% would use a future pain forecast and 80% perceived making plans (e.g. shopping, social) as a benefit. ConclusionsFor people with chronic pain, the timing of the onset of pain flares, the severity of pain flares and fluctuations in pain severity were prioritised as being key features of a pain forecast, and making plans was prioritised as being a key benefit. Plain English SummaryChronic pain is a symptom of many long-term health conditions. People with chronic pain have reported that the severity of their pain is both uncertain and unpredictable. To combat this, we want to build a pain forecast, to predict future pain severity. We hypothesise that a pain forecast would reduce pain-related uncertainty and improve quality of life. It is important that a pain forecast provides useful information to people living with chronic pain. Therefore, this work aimed to understand why participants might use a forecast, and what they would want to see in a pain forecast. A focus group was conducted to identify features, benefits and drawbacks of a pain forecast. A survey was then conducted to prioritise the features and benefits. Participants of the focus group highlighted concerns around data-sharing and potential anxiety about knowing when pain might happen. Survey participants prioritised a forecast that provided information about pain flares (periods of increased pain severity) and fluctuations in pain severity. The key perceived benefit of a forecast was the ability to make plans (such as shopping and social plans).

ObjectiveThe dynamic impact of chronic pain on attention can lead to impairments in overall cognitive functioning. Mindfulness is a practice often adopted for pain management that includes elements of attention training. It is thought to improve the experiential acceptance of pain, thus reducing pain-sensitivity and pain-related attentional biases. The aim of this study was to examine whether experience with mindfulness is associated with altered attentional functioning in participants with chronic pain. MethodsWe collected an online sample of 128 participants across four groups: 31 individuals with chronic pain who practice mindfulness (Pain-Meditators), 29 individuals with chronic pain who have not practiced mindfulness (PainNon-Meditators), 32 healthy individuals who practice mindfulness, and 36 healthy individuals who do not practice mindfulness. General attentional functioning was measured using the using the Short-Attention Network Task (short-ANT) and attention bias to pain was measured using the Pain Dot-Probe task. ResultsAn overall effect in reaction time (RT) was found across both (all p <.05), with post-hoc analyses finding that Pain-Meditators reacted faster on both the short-ANT (p = 0.014) and dot-probe attention tasks (p = < 0.001) compared to PainNon-meditators. PainNon-meditators showed higher alerting network scores on the short-ANT than all other groups (p = 0.005), indicating more reliance on cues to alert attention. No differences were found between the pain groups in attentional bias to pain-related words (p = 0.84). ConclusionThe results provide evidence that mindfulness practice is associated with altered attention performance in individuals with chronic pain and may mitigate the effects of chronic pain on attention functioning. Our results provide some of the only experimental research to investigate the effects of mindfulness training on attention processing in individuals with chronic pain.

Background Chronic pain and depression are leading causes of disability and frequently co-occur. Depression presents with diverse symptoms, but despite this variability, the prevalence of individual depressive symptoms in chronic pain and the genetic and causal associations linking these traits remain poorly characterised. Methods Using data from 142,688 age- and sex-matched UK Biobank participants, we compared depressive symptom severity levels and item-level Patient Health Questionnaire-9 (PHQ-9) prevalences, spanning affective, cognitive and somatic domains, between participants with and without chronic pain. Using genome-wide association study (GWAS) summary statistics of multisite chronic pain (MCP), major depressive disorder (MDD), and individual symptoms of depression, genetic correlations and bidirectional causal effects between MCP and depressive phenotypes (MDD and individual symptoms) were estimated via linkage disequilibrium score regression (LDSC) and two-sample Mendelian randomisation (MR), respectively. Results Depression (at every severity level) was more common in the chronic pain group compared to controls, with the largest between-group difference for severe symptoms (7.50-fold increase). All individual depressive symptoms were at least 2.79 times as prevalent in chronic pain. Additionally, chronic pain had a significant and positive genetic correlation with MDD (rg = 0.59) and all depressive symptoms (rg = [0.24, 0.55]). MR supported a bidirectional causal association between MCP and MDD (MCP[-&gt;]MDD: OR = 1.85, pFDR < 0.001, MDD[-&gt;]MCP: {beta} = 0.17, pFDR < 0.001). At the symptom level, MR indicated bidirectional effects between MCP and anhedonia (MCP[-&gt;]anhedonia: OR = 1.60, pFDR < 0.001, anhedonia[-&gt;]MCP: {beta} = 0.08, pFDR = 0.005), and unidirectional effects of MCP on appetite/weight gain (OR = 1.90, pFDR = 0.022) and appetite/weight loss (OR = 1.63, pFDR = 0.005), concentration problems (OR = 1.63, pFDR = 0.044), and suicidal thoughts (OR = 1.46, pFDR = 0.021). Additionally, genetic liability to concentration problems was associated with a lower risk of MCP ({beta} = -0.04, pFDR = 0.022). Conclusion Chronic pain is associated with a marked depressive burden spanning all symptom domains. Shared genetic architecture and symptom-specific causal pathways, particularly involving anhedonia, highlight potential targets for improved treatment of comorbid chronic pain and depression.

PurposeRural health disadvantages are well-documented in previous literature, however research on rural-urban disparities in chronic pain outcomes is scarce. This paper fills this gap by examining pain prevalences and transitions across the rural-urban continuum (i.e., large central metro, large fringe metro, medium and small metro, and nonmetropolitan). MethodsBased on the 2019-2020 National Health Interview Survey Longitudinal Cohort (NHIS-LC) data, we examined the disparities in pain prevalences and transitions among different pain states, including no pain, nonchronic pain, chronic pain and high-impact chronic pain (HICP), across the rural-urban continuum and by age, sex, race/ethnicity, and region. A test for linear trend was conducted to examine the significance of linear changes across the rural-urban continuum. FindingsThe findings reveal significant linear increases in the prevalence of chronic pain and HICP, as well as transitions from no pain to nonchronic pain and from nonchronic pain to more severe pain conditions, along the continuum from metropolitan to nonmetropolitan areas. Sub-group analyses indicate that rural-urban gaps are most pronounced among middle-aged (45-64) groups and non-Hispanic whites. ConclusionsThis study provides new evidence on rural-urban health disparities by focusing on pain, highlighting the urgent need to enhance healthcare services in remote and rural areas for effective pain prevention and management. Funding sourcesThe authors received no external financial support for the research, authorship, or publication of this article. DisclosuresThe authors declare no potential conflicts of interest with respect to the research, authorship, or publication of this article.

BackgroundAround one in five persons globally reports experiencing chronic pain. Chronic pain can lead to sleep disturbances, reduced resilience to chronic stressors, and quality of life. Exposure to childhood maltreatment is a risk factor for chronic pain that also reduces resilience abilities. However, the relationship between childhood maltreatment, resilience and sleep disturbance on quality of life in people with chronic pain remain poorly understood. MethodsTwo hundred and forty-one participants were included in this study, including 157 people with and 84 without chronic pain (controls). All participants responded to an online survey that included measures of childhood maltreatment, resilience, sleep disturbances and quality of life. A moderated serial mediation model tested how resilience and sleep disturbances mediate the relationship between group and quality of life, and how the severity of childhood maltreatment moderates the group difference in resilience. ResultsParticipants with chronic pain reported significantly lower quality of life than controls. This group difference in quality of life was significantly mediated by the level of resilience and sleep disturbance when people reported being exposed to low and average, but not high levels of childhood maltreatment. ConclusionsThe study found that exposure to childhood maltreatment reduced resilience abilities leading to more severe sleep problems and lower quality of life in participants with chronic pain. These findings suggest that interventions targeting childhood maltreatment and resilience may be beneficial to improve quality of life, through increased sleep quality, in individuals with chronic pain.

Manual therapy, such as spinal manipulation (SM), is commonly used to treat non-specific chronic low back pain (CLBP), although its mechanisms remain poorly understood. It has been hypothesized that the mechanical forces applied during spinal manipulation (SM) influence proprioceptive function, which is often impaired in patients with CLBP. This study aimed to investigate the effect of a single SM intervention on lumbar proprioceptive function and its potential relationship with analgesic effects in patients with CLBP. In a single-blind randomized controlled trial, data from 142 adults with or without CLBP were analyzed after random assignment to receive lumbar spinal manipulation (LMANIP), lumbar mobilization (LMOB), or no intervention (NI). The primary outcome was the proprioceptive weighting (PW) ratio, which reflects the central nervous systems preferred source of proprioceptive input for balance control, specifically from the lumbar and ankle muscles. PW ratios were assessed immediately before and after intervention by analyzing postural sway changes during vibrotactile stimulation (60 Hz). PW changed in both healthy participants and patients after the intervention, with a significantly stronger lumbar-steered PW following LMANIP compared to NI ({beta} = -0.047, t(422) = -2.71, p = 0.007) and LMOB ({beta} = -0.039, t(422) = - 2.17, p = 0.030). Moreover, LMANIP was particularly effective in reducing pain in patients with stronger lumbar-steered PW before intervention (p < 0.017). These findings suggest that a single SM session enhances proprioceptive input from the lumbar muscles and that the strength of the analgesic effect is associated with the baseline PW status.

BackgroundAnxiety, evoked by continuous inspiration of a 5 - 8% CO2 mixture, has been found to have an analgesic eLect on self-reported pain. The precise mechanism whereby this effect obtains remains unknown. MethodsThe present study tested whether temporal summation, the psychological counterpart of wind-up, is involved in hypercapnic analgesia. 21 healthy participants received painful transcutaneous electrical stimuli of varied intensity, during continuous inhalation of 7.5% CO2 mixture and medical air, presented in a single-blinded counterbalanced order. Continuous pain ratings were acquired to measure the temporal development of the pain response. Several points and events of interest that characterise the pain response profile were extracted from the continuous data. ResultsMixed-eLects modelling demonstrated a reduction of all pain measures during inspiration of the anxiogenic mixture, but not air. This was accompanied by an increase in the psychological and physiological measures of anxiety. Analyses of the characteristic measures of temporal summation suggested that the hypercapnic mixture has an analgesic property evident from the start of the pain response. The same was true for the remainder of the response, the adaptation period, where pain ratings were also inhibited. The reduced pain ratings persisted during the remainder of the response. Anxiety was found to be a mediating factor for summative pain ratings but not the temporally sensitive TS measures, suggesting an overall, cumulative effect. ConclusionsThe findings provide an explanation for the previously observed low self-reported pain during the inhalation of an anxiogenic hypercapnic mixture.

BackgroundEarly-life adversity (ELA) is a risk factor for enduring pain in youth and is associated with alterations in brain morphology and function. However, it remains unclear whether ELA-related neurobiological changes contribute to the development of enduring pain in early adolescence. MethodsUsing data from the Adolescent Brain Cognitive Development (ABCD) Study, we examined multimodal magnetic resonance imaging (MRI) markers in children assessed at baseline (ages 9-11 years) and at 2-year follow-up (ages 11-13 years). ELA exposure was defined at baseline to maximise temporal separation between early adversity and later enduring pain. Participants with enduring pain at follow-up (n = 322) were compared to matched pain-free controls (n = 644). Structural MRI, diffusion MRI (fractional anisotropy, mean diffusivity), and resting-state functional connectivity data were analysed. Linear models tested main effects of enduring pain, ELA, and their interaction on brain metrics, controlling for relevant covariates. ResultsELA exposure was associated with smaller caudate and nucleus accumbens volumes, and reduced surface area of the left rostral middle frontal gyrus. No significant effects of enduring pain or ELA-by-enduring pain interaction were observed across grey matter, white matter, or functional connectivity measures. ConclusionsELA was associated with alterations in fronto-striatal regions in late childhood, but these changes were not linked to enduring pain in early adolescence. These findings suggest that ELA-related neurobiological alterations may represent early markers of vulnerability rather than concurrent correlates of enduring pain. Longitudinal follow-up is needed to determine whether these alterations contribute to later chronic pain risk.

Pain intensity is difficult to predict. Mostly, because of modulatory processes underlying its formation. For example, when nociceptive stimulation occupies a larger body area, pain increases disproportionally. This modulation is called spatial summation of pain (SSp) and is responsible for coding pain intensity. To predict pain based on spatial variables, a profound understanding of the SSp effect is crucial. The aim of this study was i) to describe the SSp effect as a function of the size (or distance) of a stimulated area(s), ii) to investigate the effect of pain intensity on SSp and iii) to evaluate the influence of the SS type on the magnitude of SSp. Thirty-one healthy participants took part in a within-subject experiment. Participants were exposed to area- and distanced based SSp. In the former, electrocutaneous noxious stimuli were applied by up to 5 electrodes (5 areas) forming a line-like pattern at the ulnar side of the hand, while in the latter the same position and lengths of stimuli were used but only two electrodes were stimulated (5 separations). Each paradigm was repeated using pain of low, moderate and high intensity in a random and counterbalanced order. Each stimulus was assessed on a 0-100 scale. It was found that the pattern of increase in pain followed a logarithmic rather than a linear function. The dynamics of the pain increase were statistically different across pain intensities, with more summation occurring, if stimuli were calibrated to eliciting "high" pain. SSp was resistant to saturation in the area-based but not in the distance- based SSp, where 0.8cm separation between two electrodes produced a similar pain intensity as 1.6cm and 2.4cm. Results indicate that area-based SSp is more painful than distance-based SSp when low and moderate but not when high pain intensity is induced. Presented findings have important implications for all studies, in which the spatial dimension of pain is measured. When the area or separation between nociceptive stimulation increases, pain does not increase linearly. Furthermore, the pattern of the pain increase depends on i) intensity and ii) the number of sites of nociception. In conclusion, a logarithmic function should be considered when predicting the size of a nociceptive source. This pattern is indicative for inhibitory processes underlying SSp.

ObjectiveThis overview of systematic reviews aimed to summarize the point, annual, and lifetime prevalence of musculoskeletal pain in African countries. MethodsThe CINAHL, Embase, PsycINFO, PubMed were searched until October 6, 2023. Systematic reviews with meta-analyses evaluating the prevalence of musculoskeletal pain were included. The quality of reviews was assessed with AMSTAR 2 and the overlap among reviews was calculated. ResultsSix reviews were included. The pooled point prevalence rate of low back pain was 39%. The pooled annual prevalence rates of low back pain ranged from 54.05% to 64.07% among meta-analyses. The pooled annual prevalence rates of upper back pain, elbow pain, wrist and/or hand pain, knee and/or leg pain, foot and/or ankle pain, and hip and/or thigh pain were 27.1%, 19.7%, 24.2%, 25.0%, 20.2%, and 15.5%, respectively. The pooled lifetime prevalence rate of low back pain was 47%. A slight overlap was found among low back pain reviews. Ethiopia, Nigeria, and South Africa were mainly studied in low back pain. The rest of types of musculoskeletal pain were only studied in Ethiopia. DiscussionThe prevalence of musculoskeletal pain is high. More than 100 primary studies have been meta-analyzed on this topic, underlying the high prevalence of musculoskeletal pain in African countries. Important methodological concerns were detected and discussed that can help researchers to improve and guide the future agenda in this field. FundingNone. Review protocolhttps://doi.org/10.17605/OSF.IO/V72FY.

The locus coeruleus (LC) is a brainstem region involved in regulating pain. Chronic pain is common in older adulthood, but no studies have examined its association with the LC in humans. We used neuromelanin-sensitive imaging to study differences in LC integrity in older adults with and without chronic pain. Chronic pain was assessed in community-dwelling men from the Vietnam Era Twin Study of Aging (VETSA) in 3 study waves covering an average of 12 years. Pain was self-reported on the SF-36 Bodily Pain Scale. Chronic pain was defined as moderate to severe pain severity at the current and at least one prior wave; 17% had chronic pain (n=80). At the third wave, 481 participants (mean age=67.57) underwent neuromelanin-sensitive MRI scans from which we calculated an LC contrast-to-noise ratio (LCCNR) - an index of LC integrity. We examined associations between chronic pain and LCCNR (in the rostral LC and caudal regions) with generalized estimating equations after adjusting for age, race, education, depressive symptoms, medical comorbidities, and opioid medication use. Individuals with chronic pain had .35 standard deviation lower rostral LCCNR (95% CI: -.62 to -.05) compared to those without chronic pain. No differences in the caudal LCCNR were detected. Chronic pain was associated with decreased rostral LC integrity in older adults. Differences in the rostral LC, rather than caudal LC, suggest the association between lower LC integrity and chronic pain may be related to pain processing in cortical regions where rostral LC projections typically connect.

Background Chronic pain is associated with structural and functional brain alterations, particularly within prefrontal, insular, and cingulate cortices. The dorsolateral prefrontal cortex (DLPFC) shows consistent structural abnormalities across chronic pain conditions, whereas findings on intrinsic functional connectivity (FC) remains inconsistent. Anchoring FC analyses to structural alterations may help identify consistent patterns across chronic pain conditions. Methods We employed a voxel-based morphometry (VBM)-guided, seed-based resting-state FC approach. Structural and functional MRI data were obtained from patients with chronic neck pain (CNP; n=21) and healthy controls (HC; n=25). Regions showing significant gray matter volume (GMV) differences were used as seeds for whole-brain FC analysis. Associations with pain intensity and pain-related fear were examined. Findings were further evaluated in an independent cohort with chronic primary pain (CPP; n=38). Results VBM revealed reduced GMV in the left DLPFC in CNP compared with HC, replicated in CPP. Seed-based FC analysis demonstrated reduced connectivity between the left DLPFC and the right hippocampus in CNP, with a similar pattern in CPP. In CNP, GMV in the DLPFC was positively associated with DLPFC-hippocampal connectivity (r = 0.45, 95% CI 0.02 to 0.74, p = 0.043). Reduced DLPFC-hippocampal connectivity was associated with higher activity avoidance (r = -0.50, 95% CI -0.77 to -0.09, p = 0.021), whereas no associations were observed with pain intensity. Conclusions These findings indicate consistent structural and functional alterations across chronic pain cohorts. Reduced DLPFC-hippocampal connectivity may reflect altered interactions between prefrontal and hippocampal circuits involved in pain-related cognitive and affective processes.

The human hand has a refined mechanical sensitivity, allowing it to play crucial roles in tactile exploration and object manipulation. Despite its fundamental and clinical relevance, a comprehensive characterization of mechanical sensitivity across the human palm is still lacking. Here, we mapped the spatial distribution of innocuous and noxious mechanical sensitivity across the palmar surface of the human hand. We examined 66 hands from 33 healthy adults, dividing the palm into 27 areas, in each of which we measured the mechanical detection threshold, the mechanical pain threshold and the pain intensity evoked by a standard 300 g pinprick stimulus. We found distal areas (i.e., fingertips) to exhibit higher tactile sensitivity than proximal areas (i.e., the wrist). Notably, the sensitivity to innocuous and noxious mechanical stimuli were inversely correlated across areas, such that areas with higher tactile sensitivity displayed higher pain thresholds. In addition, the dominant hand was less sensitive than the non-dominant one, and women displayed higher sensitivity than men. Together, this work provides the first detailed spatial characterization of mechanical sensitivity across the human hand and introduces a systematic methodology for its assessment. These findings set the stage for future studies of the neurophysiological mechanisms of touch and pain in the human hand and for clinical research into pathological conditions involving the altered hand sensitivity.

Background Chronic pain and depression are prevalent and burdensome conditions that frequently co-occur. Separate neuroimaging studies of each disorder suggest overlapping brain-structure alterations, however, relatively few studies have examined their comorbidity directly, and the neuroanatomical profile of co-occurring chronic pain and depression remains unclear. Methods Using UK Biobank data (n = 71,214), we conducted cross-sectional pairwise association analyses of brain structure (cortical measures, subcortical volumes, and white matter microstructure) comparing participants with current comorbid chronic pain and depression, current chronic pain only, current depression only, and controls. Results Compared with controls, the comorbidity group showed regional differences in cortical surface area and thickness ({beta} range = -0.096 to 0.098, pFDR < 0.05), widespread lower cortical volume ({beta} range = -0.096 to -0.050, pFDR < 0.05), lower thalamic (left: {beta} = -0.048, pFDR = 0.038; right: {beta} = -0.060, pFDR = 0.007), hippocampal (left: {beta} = -0.062, pFDR = 0.035; right: {beta} = -0.088, pFDR = 0.002) and left accumbens volume ({beta} = -0.073, pFDR = 0.011), and evidence of widespread white matter microstructure alterations (fractional anisotropy: {beta} range = -0.116 to -0.080, pFDR < 0.05; mean diffusivity: {beta} range = 0.063 to 0.137, pFDR < 0.05). Pairwise comparisons with the disorder-specific groups also identified several alterations unique to the comorbidity group. Compared to controls, those with chronic pain only had widespread lower cortical surface area and volume ({beta} range = -0.043 to -0.015, pFDR < 0.05), whereas non-comorbid depression showed more regionally specific lower cortical thickness and volume ({beta} range = -0.140 to -0.062, pFDR < 0.05) and lower thalamic volume (left: {beta} = -0.067, pFDR = 0.016; right: {beta} = -0.066, pFDR = 0.015), alongside widespread white matter microstructure deficits (fractional anisotropy: {beta} range = -0.104 to -0.083, pFDR < 0.05; mean diffusivity: {beta} range = 0.079 to 0.149, pFDR < 0.05). Conclusion These results provide a robust characterisation of brain structure alterations in comorbid chronic pain and depression, highlighting a distinct neuroanatomical profile and advancing understanding of its underlying neurobiology.