European Journal of 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.

Objective: There is a bidirectional relationship between emotional distress and pain. However, this relationship is understudied in people with HIV in low-resource settings. This study sought to describe the temporal relationship between emotional distress and pain in people with HIV. Design: Longitudinal observational study. Methods: Participants with virally suppressed HIV, reporting either no pain or persistent pain at baseline, provided weekly remote ratings of distress, worst pain, and average pain using 0-10 visual analogue scales. Within-individual fluctuations in distress and pain were visualised over time. Group-level correlations were determined using Spearman's correlation tests. Cumulative link mixed models assessed whether distress and pain each predicted the other in the following week. Results: 72 participants provided responses over 49 weeks. The participants had a median (IQR) age of 43 (37-51) years, 63% (n=45) were unemployed and most were females (n=51;71%). Distress and pain fluctuated concurrently within individuals: distress was positively correlated with worst pain ({rho}=0.66, 95% CI= 0.60-0.72, p<0.001) and average pain ({rho}=0.70, 95% CI=0.64-0.75, p<0.001) intensity within the same week. Worst pain (OR=1.42, 95% CI=1.17-1.71, p<0.001) and average pain (OR=1.43, 95% CI=1.20-1.71, p<0.001) intensity both predicted distress in the next week. Distress predicted worst pain intensity (OR=1.25, 95% CI=1.07-1.46, p=0.023) but not average pain intensity (OR=1.19, 95% CI=1.01-1.40, p=0.152) in the next week. Conclusions: The temporal relationship between distress and worst pain intensity was bidirectional, whereas distress did not temporally predict average pain intensity. Both pain and emotional distress should receive attention from HIV research and clinical care in low-resource settings.

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.

Chronic pain is highly heterogeneous, with individuals varying substantially in symptoms. pain severity, disability, affective distress, cognitive functioning, and trauma-related symptoms. This study examined whether working memory, post-traumatic stress symptoms (PTSS), trauma exposure, and pain modulation explain distinct or shared dimensions of chronic pain variability. Individuals with chronic pain completed clinical, cognitive, trauma-related, and behavioural pain modulation measures, as well as resting-state functional magnetic resonance imaging. Multivariate regressions were used to determine whether working memory, PTSS, trauma exposure, and pain modulation independently predicted chronic pain outcomes. Principal component analysis was used to identify latent dimensions of chronic pain, and mediation analyses tested whether behavioural pain modulation explained relationships between dlPFC to vlPAG resting-state functional connectivity and clinical pain outcomes. PTSS independently predicted affective outcomes, including depression, state anxiety, and trait anxiety, whereas working memory independently predicted pain severity and pain interference. Trauma exposure was associated with greater PTSS and poorer working memory, but did not independently predict core pain outcomes after accounting for these more proximal factors. Principal component analysis identified partially distinct affective and sensory-disability dimensions, while trauma exposure loaded primarily on a separate component characterized by greater PTSS and poorer working memory. Behavioural pain modulation showed broader relationships across symptom dimensions and was associated with dlPFC to vlPAG connectivity. Exploratory mediation analyses demonstrated that pain modulation mediated relationships between dlPFC to vlPAG connectivity and both pain severity and affective distress. These findings support an integrated model where PTSS and working memory are more proximal predictors of affect and severity respectively, and trauma exposure represents a more distal vulnerability factor that predicts both. Thus, pain modulation represents a shared mechanism linking cortico-brainstem connectivity to chronic pain intensity and affect. These variables need further testing for phenotyping people with chronic pain based on their specific clinical needs.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

IntroductionOne in five Canadians lives with chronic pain. Evidence shows that some individuals experience pain that fluctuates in intensity following a circadian (24-hour) rhythm. Endogenous molecular rhythms regulate the function of most physiological processes, neuroimmunology functions that govern pain mechanisms. Addressing chronic pain rhythmicity on a molecular and biopsychosocial level can advance understanding of the disease and identify new treatment/management strategies. Our CircaHealth CircaPain study uses an online survey combined with ecological momentary assessments and bio-sample collection to investigate the circadian control of chronic pain and identify potential biomarkers. Our primary objective is to understand inter-individual variability in pain rhythmicity, by collecting biopsychosocial measures. The secondary objective accounts for seasonal variability and the effect of latitude on rhythmicity. Methods and analysisFollowing completion of a baseline questionnaire, participants complete a series of electronic symptom-tracking diaries to rate their pain intensity, negative affect, and fatigue on a 0-10 scale at 8:00, 14:00, and 20:00 daily over 10 days. These measures are repeated at 6- and 12-months post-enrolment to account for potential seasonal changes. Infrastructure is being developed to facilitate the collection of blood samples from subgroups of participants 2 times per day over 24-48 hours to identify rhythmic expression of circulating genes and/or proteins. Ethics and disseminationEthical approval for this study was obtained by the Queens University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board. Findings will be published in a relevant scientific journal and disseminated at national and international scientific meetings and online webinars. We maintain a website to post updated resources and engage with the community. We employ knowledge mobilization in the form of direct data sharing with participants. This study is funded by the Canadian Institutes of Health Research (CIHR) (grant PJT-497592) and the CIHR Strategy for Patient-Oriented Research (SPOR) Chronic Pain Network (CPN) (grant SCA-145102). Ethical approval date: 08 March 2024 Estimated start of the study: April 2024 Strengths and limitations of this studyO_LIData will be collected using self-report questionnaires only, which may lead to random or systematic misreporting. C_LIO_LIThe online nature of the study might affect the diversity in our sample (e.g., the representation of rural and/or underprivileged communities). C_LIO_LIPhysical distance from research laboratories with specialized equipment for analyses and biobanking storage might affect accessibility, however, this can be overcome by using mailable dried blood spot collection kits as described. C_LIO_LIQuestionnaires used in our study have previously been validated in the chronic pain population and used in several languages. C_LIO_LIUncovering distinct pain rhythmicity patterns and health outcomes associated with rhythmicity may help develop new treatments for different chronic pain conditions tailored to individual circadian rhythms. C_LI

BackgroundChronic pain is associated with heightened prevalence of trauma exposure. Separate studies of chronic pain and trauma report overlapping brain alterations in older adults (age over 60). Despite this close relationship, the interplay between chronic pain and trauma on brain morphology remains poorly understood. MethodsTabulated T1-weighted structural magnetic resonance imaging data were accessed from the UK biobank (N = 21,996). Linear mixed models were used to determine the main effects of group (control versus chronic pain), severity of trauma exposure and their interaction on measures of surface area, cortical thickness and subcortical volume. To examine the unique and cumulative impacts of trauma exposure at different developmental timing, group of participants exposed to childhood maltreatment only, trauma in adulthood only and both were derived. ResultsIndependently of the severity of trauma exposure, chronic pain was significantly associated with smaller surface area and thicker frontal, temporal, parietal, somatosensory, occipital and cingulate cortices. Independently of chronic pain, the severity of trauma exposure in adulthood and both childhood and adulthood, but not childhood alone, were associated with smaller bilateral nucleus accumbens, putamen, thalamus and left hippocampal volumes, as well as left inferior parietal gyrus surface area. No chronic pain-by-trauma severity interactions were significantly associated with variations in any regional measures. ConclusionsSpecific effects of chronic pain and trauma severity were evident among older adults exposed to trauma at different developmental timing. However, there was no evidence for unique brain signatures representing the combined effects of chronic pain and trauma in older adults.