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The evaluation of chronic pain is challenging because of the lack of specific biomarkers. We identified the Mu opioid receptor-positive (Mu+) B cell percentage of expression, named Mu-Lympho-Marker (MLM), as a candidate marker for chronic pain in fibromyalgia (FM) and osteoarthritis (OA) patients. Here, we investigate the role of MLM on natural killer (NK) cells in the same patients. Twenty-nine FM and twelve OA patients were analyzed, and twenty-three pain-free subjects were considered as the control group. Blood samples were collected to perform immunophenotyping and Western blot analysis. Biological and clinical data were statistically analyzed. The final results showed that the percentage of NK cells expressing Mu was statistically lower in FM and OA patients than in pain-free subjects, as already demonstrated for B cells. A Western blot analysis was performed in order to detect NK cells' functional status. Moreover, the correlation analysis of MLM expression with pharmacological therapy did not show any significant results. In conclusion, here, we confirm the role of MLM as a suitable marker for chronic pain and underline NK cells as a new possible immune cell type involved in the "Mu opioid receptor reserve theory". [ABSTRACT FROM AUTHOR]

Chronic pain represents one of the most serious worldwide medical problems, in terms of both social and economic costs, often causing severe and intractable physical and psychological suffering. The lack of biological markers for pain, which could assist in forming clearer diagnoses and prognoses, makes chronic pain therapy particularly arduous and sometimes harmful. Opioids are used worldwide to treat chronic pain conditions, but there is still an ambiguous and inadequate understanding about their therapeutic use, mostly because of their dual effect in acutely reducing pain and inducing, at the same time, tolerance, dependence, and a risk for opioid use disorder. In addition, clinical studies suggest that opioid treatment can be associated with a high risk of immune suppression and the development of inflammatory events, worsening the chronic pain status itself. While opioid peptides and receptors are expressed in both central and peripheral nervous cells, immune cells, and tissues, the role of opioids and their receptors, when and why they are activated endogenously and what their exact role is in chronic pain pathways is still poorly understood. Thus, in this review we aim to highlight the interplay between pain and immune system, focusing on opioids and their receptors. [ABSTRACT FROM AUTHOR]

Objective: The chronic pain syndromes (CPS) include syndromes such as chronic widespread pain (CWP), dry eye disease (DED) and irritable bowel syndrome (IBS). Highly prevalent and lacking pathognomonic biomarkers, the CPS are known to cluster in individuals in part due to their genetic overlap, but patient diagnosis can be difficult. The success of quantitative sensory testing (QST) and inflammatory biomarkers as phenotyping tools in conditions such as painful neuropathies warrant their investigation in CPS. We aimed to examine whether individual QST modalities and candidate inflammatory markers were associated with CWP, DED or IBS in a large, highly phenotyped population sample., Design: Cross-sectional study., Setting: Community-dwelling cohort., Participants: Twins from the TwinsUK cohort PRIMARY AND SECONDARY OUTCOME MEASURES: We compared 10 QST modalities, measured in participants with and without a CWP diagnosis between 2007 and 2012. We investigated whether inflammatory markers measured by Olink were associated with CWP, including interleukin-6 (IL-6), IL-8, IL-10, monocyte chemoattractant protein-1 and tumour necrosis factor. All analyses were repeated in DED and IBS with correction for multiple testing., Results: In N=3022 twins (95.8% women), no association was identified between individual QST modalities and CPS diagnoses (CWP, DED and IBS). Analyses of candidate inflammatory marker levels and CPS diagnoses in n=1368 twins also failed to meet statistical significance., Conclusion: Our findings in a large population cohort suggest a lack of true association between singular QST modalities or candidate inflammatory markers and CPS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Most Americans live in a state that has legalized cannabis as a medical treatment for pain, but it is unclear how chronic pain intensity relates to cannabis use. Our objective was to examine the association between patient-reported pain measures and cannabis among adults with chronic pain., Methods: This cross-sectional study of a representative sample of adults reporting chronic non-cancer pain in 36 states and DC with active medical cannabis programs from March to April 2022 assessed cannabis use for chronic pain, categorized as active (within 30 days), past (>31 days), or never use (referent). Measures were pain intensity (primary) and interference, Widespread Pain Index, and number of chronic pain diagnoses., Results: Among 1628 participants (57% female, 69% white), 352 (22%) actively used cannabis to treat chronic pain, 137 (8%) reported past cannabis use, and 1139 (70%) never used cannabis. In adjusted models, active cannabis use was associated with higher scores for pain intensity (score difference 1.03, 95% CI 0.05 to 2.02) and pain interference (score difference 1.82, 95% CI 0.99 to 2.65) compared with never use. Persons who actively used cannabis had higher Widespread Pain Index scores (score difference 0.56, 95% CI 0.26 to 0.86) and more chronic pain diagnoses (difference 0.45, 95% CI 0.06 to 0.83)., Conclusion: People with chronic non-cancer pain who used cannabis for pain reported non-clinically meaningful worse pain measures and greater burden of chronic pain conditions than their counterparts who never used cannabis. Alternatively, those with worse pain and greater burden of pain appear more likely to use cannabis., Competing Interests: Competing interests: MCB reports current grants from PCORI, CDC, NIH, Michigan Department of Health and Human Services and past grants from the Arnold Foundation. The other authors report no conflicts of interest., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: In this study, we describe the development and validation of a revised Pediatric Chronic Pain Grading (P-CPG) for children aged 8 to 17 years that adds emotional impairment to previously used measures of pain intensity and functional impairment. Such a measure enables the assessment of chronic pain severity in different epidemiological and clinical populations, the stratification of treatment according to pain severity, and the monitoring of treatment outcome. The P-CPG was developed using a representative sample of school children with chronic pain (n = 454; M age = 12.95, SD = 2.22). Construct validity and sensitivity to change were examined within a sample of N = 2448 children and adolescents (M age = 12.71, SD = 2.47) comprising 3 subsamples (school n = 1562, primary care n = 129, and tertiary care n = 757) affected by chronic pain to varying extents. Results showed that P-CPG grades differed significantly among the 3 subsamples, with school children being least affected by chronic pain and tertiary care patients being most affected. As P-CPG grade increased, so did pain intensity, functional impairment, pain-related school absence, and emotional impairment. Convergent validity was demonstrated by significant positive correlations between the P-CPG and global ratings of pain severity as well as objective claims data; the latter reflects greater health care costs with increasing P-CPG scores. Sensitivity to change was supported by a significant reduction in baseline P-CPG grades 3 and 6 months after intensive interdisciplinary pain treatment in tertiary care sample. In conclusion, the P-CPG is an appropriate measure of pain severity in children and adolescents with chronic pain in clinical as well as epidemiological settings., (Copyright © 2024 International Association for the Study of Pain.)

Abstract: Ecological momentary assessment (EMA) allows for the collection of participant-reported outcomes (PROs), including pain, in the normal environment at high resolution and with reduced recall bias. Ecological momentary assessment is an important component in studies of pain, providing detailed information about the frequency, intensity, and degree of interference of individuals' pain. However, there is no universally agreed on standard for summarizing pain measures from repeated PRO assessment using EMA into a single, clinically meaningful measure of pain. Here, we quantify the accuracy of summaries (eg, mean and median) of pain outcomes obtained from EMA and the effect of thresholding these summaries to obtain binary clinical end points of chronic pain status (yes/no). Data applications and simulations indicate that binarizing empirical estimators (eg, sample mean, random intercept linear mixed model) can perform well. However, linear mixed-effect modeling estimators that account for the nonlinear relationship between average and variability of pain scores perform better for quantifying the true average pain and reduce estimation error by up to 50%, with larger improvements for individuals with more variable pain scores. We also show that binarizing pain scores (eg, <3 and ≥3) can lead to a substantial loss of statistical power (40%-50%). Thus, when examining pain outcomes using EMA, the use of linear mixed models using the entire scale (0-10) is superior to splitting the outcomes into 2 groups (<3 and ≥3) providing greater statistical power and sensitivity., (Copyright © 2024 International Association for the Study of Pain.)

Purpose: During follow-up, patients in remission after oral or oropharyngeal cancer are few to express pain, depression or anxiety, their chief complain are dry mouth and difficulties to chewing. The aim of the study is to estimate prevalence of pain, quality of life and their evolution over four years., Methods: This prospective observational study included 21 patients between June and September 2017. Clinical examination, neurosensory examination and questionnaires (using visual analogic scale DN4, PCS-CF, HADS EORTC QLQ30 and H&N 35) were performed and a second time 4 years later., Results: After 4 years, 17 patients could be reviewed. In 2017 as in 2021, two patients (11.8 %) experience neuropathic pain. In 2017, 14 (82.3 %) reported paresthesia or dysesthesia or hypo/anesthesia, none of them have provoked pain to a mechanical or thermal stimulus. In 2021, only 9 (53 %) still report those symptoms. Global analysis of the questionnaire QLQC30 reveals a significant increase quality of life of all 17 patients (p = 0.0003). For the two questionnaires QLQC30 and QLQ-H&N 35, dry mouth, sticky saliva, difficulties for eating and relation with food, are strong grievances which an absence of amelioration or a degradation., Conclusions: Neurosensory disturbance is a frequent symptom but pain concerns only 11.8 % of patients. Quality of life increase globally, yet difficulties concerning oral cavity functions endure., Implications for Cancer Survivors: For remission patients, pain is an unfrequent situation unlike neurosensory disturbance. Support care improve life quality. In case of onset of pain, recurrence and osteoradionecrosis should be mentioned immediately., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier Masson SAS.)

In both pain research and clinical practice, patient-reported outcome measures are used to assess dimensions of health. Interpreting these instruments requires understanding their measurement error and what magnitude of change has subjective importance for patients. This study estimated the standard error of measurement, 1-year minimal detectable change, and 1-year minimal clinically important difference (MCID) for the Short Form-36 Health Survey physical component summary and mental component summary, the Hospital Anxiety and Depression Scale subscales for anxiety symptoms and depression symptoms, and the numeric rating scale for past-week average pain intensity. MCIDs for these instruments have not previously been estimated in a large sample of chronic pain patients participating in interdisciplinary pain rehabilitation. Data were drawn from the Swedish Quality Registry for Pain Rehabilitation (n = 8,854 patients). MCID was estimated as average change and change difference based on 3 different anchors. MCID estimates were 2.62 to 4.69 for Short Form-36 Health Survey physical component summary, 4.46 to 6.79 for Short Form-36 Health Survey mental component summary, .895 to 1.48 for numeric rating scale, 1.17 to 2.13 for anxiety symptoms in the Hospital Anxiety and Depression Scale, and 1.48 to 2.54 for depression symptoms in the Hospital Anxiety and Depression Scale. The common assumption of an identical standard error of measurement for pre- and post-treatment measurements was not always applicable. When estimating MCID, researchers should select an estimation method and anchor aligned with the study's context and objectives. PERSPECTIVE: This article presents estimates of MCID and minimal detectable change for several commonly used patient-reported outcome measures among patients with chronic pain. These estimates can help clinicians and researchers to determine when a measured health improvement is subjectively important to the patient and greater than measurement error., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Amidst broad changes to the somatic disorder diagnoses, DSM-IV pain disorder was absorbed into DSM-5's somatic symptom disorder (SSD) as a specifier. However, clinical research testing of its use for the chronic pain population has been limited and its utility remains inconclusive. Using the exemplar of fibromyalgia, this article evaluates the validity, reliability, clinical utility, and acceptability of the SSD pain specifier. The diagnosis appears to have moderate validity but low specificity for the fibromyalgia population. The pain specifier has neither undergone sufficient field testing nor been evaluated for use by medical providers, with available data suggesting low reliability. Further research is needed to establish clinical utility via assessment of differential treatment outcomes. Concerns about social, legal, and economic consequences of classifying pain patients with a mental health diagnosis are outstanding. The current SSD criteria should be used with caution among the fibromyalgia patient population until its application for chronic pain has been further researched., (© 2024. The Author(s).)

Increasing evidence is present to enable pain measurement by using frontal channel EEG-based signals with spectral analysis and phase-amplitude coupling. To identify frontal channel EEG-based biomarkers for quantifying pain severity, we investigated band-power features to more complex features and employed various machine learning algorithms to assess the viability of these features. We utilized a public EEG dataset obtained from 36 patients with chronic pain during an eyes-open resting state and performed correlation analysis between clinically labelled pain scores and EEG features from Fp1 and Fp2 channels (EEG band-powers, phase-amplitude couplings (PAC), and its asymmetry features). We also conducted regression analysis with various machine learning models to predict patients' pain intensity. All the possible feature sets combined with five machine learning models (Linear Regression, random forest and support vector regression with linear, non-linear and polynomial kernels) were intensively checked, and regression performances were measured by adjusted R-squared value. We found significant correlations between beta power asymmetry (r = -0.375), gamma power asymmetry (r = -0.433) and low beta to low gamma coupling (r = -0.397) with pain scores while band power features did not show meaningful results. In the regression analysis, Support Vector Regression with a polynomial kernel showed the best performance (R squared value = 0.655), enabling the regression of pain intensity within a clinically usable error range. We identified the four most selected features (gamma power asymmetry, PAC asymmetry of theta to low gamma, low beta to low/high gamma). This study addressed the importance of complex features such as asymmetry and phase-amplitude coupling in pain research and demonstrated the feasibility of objectively observing pain intensity using the frontal channel-based EEG, that are clinically crucial for early intervention., (© 2024. The Author(s).)

Purpose: To assess the test-retest and inter-rater reliability of goniometry and fleximetry in measuring cervical range of motion in individuals with chronic neck pain., Methods: A reliability study. Thirty individuals with chronic neck pain were selected. Cervical range of motion was measured by goniometry and fleximetry at two time points 7 days apart. To characterize the sample, we used the numerical pain rating scale, Pain-Related Catastrophizing Thoughts Scale, and Neck Disability Index. Intraclass correlation coefficient (ICC), standard error of measurement (SEM) and minimum detectable change (MDC) were calculated. Correlations between goniometry and fleximetry measurements were performed using Spearman's correlation coefficient (rho)., Results: For goniometry, we found excellent test-retest reliability (ICC ≥ 0.986, SEM ≤ 1.89%, MDC ≤ 5.23%) and inter-rater reliability (ICC ≥ 0.947, SEM ≤ 3.91%, MDC ≤ 10.84%). Similarly, we found excellent test-retest reliability (ICC ≥ 0.969, SEM ≤ 2.71%, MDC ≤ 7.52%) and inter-rater reliability (ICC ≥ 0.981, SEM ≤ 1.88%, MDC ≤ 5.20%) for fleximetry. Finally, we observed a strong correlation between the goniometry and the fleximetry for all cervical movements (rho ≥ 0.993)., Conclusion: Goniometry and fleximetry measurements are reliable for assessing cervical range of motion in individuals with chronic neck pain., (© 2024. The Author(s).)

Assessing physical activity is important in the treatment of chronic conditions, including chronic low back pain (cLBP). ActiGraph™, a widely used physical activity monitor, collects raw acceleration data, and processes these data through proprietary algorithms to produce physical activity measures. The purpose of this study was to replicate ActiGraph™ algorithms in MATLAB and test the validity of this method with both healthy controls and participants with cLBP. MATLAB code was developed to replicate ActiGraph™'s activity counts and step counts algorithms, to sum the activity counts into counts per minute (CPM), and categorize each minute into activity intensity cut points. A free-living validation was performed where 24 individuals, 12 cLBP and 12 healthy, wore an ActiGraph™ GT9X on their non-dominant hip for up to seven days. The raw acceleration data were processed in both ActiLife™ (v6), ActiGraph™'s data analysis software platform, and through MATLAB (2022a). Percent errors between methods for all 24 participants, as well as separated by cLBP and healthy, were all less than 2%. ActiGraph™ algorithms were replicated and validated for both populations, based on minimal error differences between ActiLife™ and MATLAB, allowing researchers to analyze data from any accelerometer in a manner comparable to ActiLife™.

Background: People with chronic musculoskeletal pain (CMSP) often have low physical activity. Various factors can influence the activity level. The aim of this study was to monitor physical activity, assessed by the number of steps per day, over time in people with CMSP and identify factors that could be associated with this activity feature., Methods: This prospective study involved people undergoing rehabilitation following an orthopedic trauma that had led to CMSP. At entry, participants completed self-reported questionnaires assessing pain, anxiety, depression, catastrophyzing, kinesiophobia, and behavioural activity patterns (avoidance, pacing and overdoing). They also underwent functional tests, assessing walking endurance and physical fitness. To determine daily step counts, participants wore an accelerometer for 1 week during rehabilitation and 3 months post-rehabilitation. The number of steps per day was compared among three time points: weekend of rehabilitation (an estimate of pre-rehabilitation activity; T1), weekdays of rehabilitation (T2), and post-rehabilitation (T3). Linear regression models were used to analyze the association between daily steps at T2 and at T3 and self-reported and performance-based parameters., Results: Data from 145 participants were analyzed. The mean number of steps was significantly higher during T2 than T1 and T3 (7323 [3047] vs. 4782 [2689], p < 0.001, Cohen's d = 0.769, and 4757 [2680], p < 0.001, Cohen's d = 0.693), whereas T1 and T3 results were similar (p = 0.92, Cohen's d = 0.008). Correlations of number of steps per day among time points were low (r ≤ 0.4). Multivariable regression models revealed an association between daily steps at T2 and pain interfering with walking, anxiety and overdoing behaviour. Daily steps at T3 were associated with overdoing behaviour and physical fitness., Conclusions: Despite chronic pain, people in rehabilitation after an orthopedic trauma increased their physical activity if they were given incentives to do so. When these incentives disappeared, most people returned to their previous activity levels. A multimodal follow-up approach could include both therapeutic and environmental incentives to help maintain physical activity in this population., (© 2024. The Author(s).)

Background: Calf circumference is currently recommended as a case-finding marker for sarcopenia, but its usefulness has not been determined in chronic pain conditions. Therefore, the present study aimed to evaluate the predictive performance of calf circumference in diagnosing sarcopenia in older patients with chronic low back pain., Methods: Ambulatory adult patients aged ≥ 65 years with chronic low back pain were enrolled. A diagnosis of sarcopenia was established based on the criteria outlined by the Asian Working Group for Sarcopenia in 2019. Patient demographics, pain-related factors, clinical factors, and sarcopenia-related measurements were compared between non-sarcopenic and sarcopenic patients. Linear regression analysis was used to evaluate the correlation of calf circumference with muscle mass, strength, and physical performance. Also, a receiver operating characteristic curve analysis for calf circumference in predicting sarcopenia was conducted; and area under the curve (AUC) values, along with their corresponding 95% confidence intervals (CI), were calculated., Results: Data from 592 patients were included in the analysis. Eighty-five patients were diagnosed with sarcopenia (14.3%), 71 of whom had severe sarcopenia (11.9%). A higher prevalence of sarcopenia was observed in female patients (9.0% vs. 16.7%, p = 0.016). After adjusting for age, BMI, and comorbidities, calf circumference correlated positively with muscle mass but not with muscle strength and physical performance. The AUC values for sarcopenia were 0.754 (95% CI = 0.636-0.871, p = 0.001) in males and 0.721 (95% CI = 0.657-0.786, p < 0.001) in females. The cut-offs for calf circumference in predicting sarcopenia were 34 cm (sensitivity 67.1%, specificity 70.6%) in males, and 31 cm (sensitivity 82.5%, specificity 51.5%) in females., Conclusions: Even though sex differences in its predictive value for sarcopenia should be considered, our findings suggest that calf circumference can be used as an indicator for predicting muscle mass and may serve as a potential marker for identifying sarcopenia in older patients with chronic low back pain., (© 2024. The Author(s).)

Background: Vulvodynia is a chronic pain condition without an identifiable cause. As such, it is a diagnosis of exclusion, and all other causes of vulvar pain should be excluded. Although a standard treatment for vulvodynia has not been established yet, multidisciplinary care programs appear to be effective., Puropose: The aim of this retrospective monocentric study was to analyze the prevalence of vulvodynia among women referred to our institution for a suspected diagnosis and to evaluate the efficacy of a multidimensional treatment plan. The primary outcome was the prevalence of vulvodynia following differential diagnosis. Secondary outcomes included: prevalence of the differential diagnoses, symptom resolution rate following treatment, and the relation between persistence of symptoms and (a) patients' age; (b) coexisting chronic overlapping pain conditions (COPCs)., Results: After having ruled out all other causes of vulvar pain, only 40.1% of women were considered as affected by vulvodynia. The most frequent differential diagnoses included lower genital tract infections (25.3%), vulvar lichen sclerosus (17.6%) and vulvovaginal atrophy (8.2%). Following a multidisciplinary care program, resolution of symptoms was observed in 13.6% cases, improvement in 64.3% and persistence in 21.9%. We did not find a statistically significant association between persistence of symptoms and age > 38 years (OR 2.10; p = 0.30). Women with one or more COPCs other than vulvodynia had a 75% increased risk of not obtaining a resolution of symptoms (OR 1.75; p = 0.44)., Conclusion: A thorough differential diagnosis and a multidisciplinary care program may represent a first way out of the muddle in the management of these patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The Pain Responses Scale and its Short Form (PRS-SF) were recently developed to assess the affective, behavioral, and cognitive responses to pain based on the behavioral inhibition system (BIS) and behavioral activation system (BAS) model of chronic pain. The purpose of this study was to provide additional tests of the psychometric properties of the PRS-SF in a new sample of individuals with chronic pain., Methods: A sample of Spanish adults (N = 190) with chronic non-cancer pain completed a translated version of the PRS-SF and a battery of questionnaires measuring validity criteria hypothesized the be associated with BIS and BAS activation, including measures of sensitivity to punishment, sensitivity to reward, pain intensity, pain interference, catastrophizing, and pain acceptance., Results: Confirmatory factor analysis supported a 4-factor structure for the PRS-SF assessing despondent, escape, approach, and relaxation responses (S-B χ 2 [5] = 1.49, Comparative Fit Index = 0.99, Non-Normed Fit Index = 0.99, root-mean-square error of approximation = 0.051, Akaike Information Criterion = 4113.66), with marginal internal consistency for 1 scale (relaxation) and adequate to good internal consistency for the others. The pattern of associations found between the PRS-SF Scale scores and the validity criterion supports the validity of the instrument., Conclusion: The results provide additional support for the validity of the 4 PRS-SF Scale scores, and the reliability of 3 of the scales. If these findings are replicated in future research, investigators may wish to administer more items from the original Relaxation Scale when assessing this domain to ensure adequate reliability for this scale. The other items from the PRS-SF assessing despondent, escape, and approach responses appear to provide at least adequate reliability. When used in this way, the PRS-SF may be used to measure BIS and BAS responses to pain to: (1) provide further tests of the BIS-BAS model of chronic pain and/or (2) understand the potential mediating effects of BIS and BAS responses on the effects of psychological pain treatments to help determine which specific responses are most responsible for the benefits of treatment, and, therefore, which responses should be specifically targeted to enhance treatment response., Competing Interests: This research was supported in part by Spanish Ministry of Science and Innovation (Madrid, Spain, Grant number: PID2019-106086RB-I00) and by the Regional Council of Economy and Knowledge (Andalusian Regional Government, Sevilla, Spain, Grant number: UMA20-FEDERJA-118). In addition, this research was also supported by another grant from the Ministerio de Ciencia e Innovación (Spain, Programa de Formación de Profesorado Universitario, Grant number: FPU20/05484) to GST. R.V. is supported by the Spanish Ministry of Science and Innovation with a Ramón y Cajal contract (RYC2018-024722-I). The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Though pain sensitivity impairments contribute to chronic pain in younger adults, it is unclear if pain hypersensitivity manifests with aging and is heightened in the geriatric chronic low back pain population. The cross-sectional study preliminarily addressed this gap by measuring pain sensitivity in older adults with chronic low back pain (n = 25) as well as pain-free sex-matched older (n = 25) and younger adults (n = 25). Pain sensitivity was quantified by 8 distinct measures that were subdivided as static (ie, pressure pain thresholds, heat pain thresholds, fixed mechanical pain, and fixed cold pain) and dynamic pain sensitivity (ie, mechanical temporal summation, thermal ramp and hold, heat pain aftersensations, and conditioned pain modulation). Test-retest reliability values for pain sensitivity ranged from moderate to excellent (intraclass correlation coefficients ≥ .500; p's < .05). The main effect for the group was significant (partial η 2 = .413, P < .001), revealing between-group differences in pain sensitivity on 5 out of 8 tests (p's ≤ .043). Predominantly, both older adult groups demonstrated increased pain facilitation and decreased pain inhibition during dynamic pain sensitivity testing compared to pain-free younger adults (p's ≤ .044). Despite qualitative differences, static and dynamic pain sensitivity responses were statistically similar between older adults with and without chronic LBP (p's > .05). Findings suggest pain sensitivity can be reliably measured in older adults and that pain hypersensitivity develops with chronological aging, providing partial support for the theory that pain hypersensitivity may impact geriatric chronic pain populations. Further study is needed to more definitively parse out whether pain hypersensitivity is comparatively heightened in older adults with chronic LBP beyond the influence of chronological aging. PERSPECTIVE: This article establishes that surrogate measures of centrally mediated pain sensitization are heightened with aging. Impaired endogenous pain modulation may influence chronic pain development, maintenance, treatment efficacy, and/or ensuing disability, necessitating research to comprehensively characterize how pain hypersensitivity contributes to geriatric chronic pain conditions., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to identify meaningful response patterns in self-report survey data collected from Canadian military veterans with chronic pain and to create an algorithm intended to facilitate triage and prioritization of veterans to the most appropriate interventions. An online survey was presented to former members of the Canadian military who self-identified as having chronic pain. Variables collected were related to pain, physical and mental interference, prior traumatic experiences, and indicators from each of the 7 potential drivers of the pain experience. Maximum likelihood estimation-based latent profile analysis was used to identify clinically and statistically meaningful profiles using the 7-axis variables, and classification and regression tree (CRT) analysis was then conducted to identify the most parsimonious set of indicators that could be used to accurately classify respondents into the most relevant profile group. Data from N = 322 veterans were available for analysis. The results of maximum likelihood estimation-based latent profile analysis indicated a 5-profile structure was optimal for explaining the patterns of responses within the data. These were: Mood-Dominant (13%), Localized Physical (24%), Neurosensory-Dominant (33%), Central-Dominant with complex mood and neurosensory symptoms (16%), and Trauma- and mood-dominant (14%). From CRT analysis, an algorithm requiring only 3 self-report tools (central symptoms, mood screening, bodily coherence) achieved 83% classification accuracy across the 5 profiles. The new classification algorithm requiring 16 total items may be helpful for clinicians and veterans in pain to identify the most dominant drivers of their pain experience that may be useful for prioritizing intervention strategies, targets, and relevant health care disciplines. PERSPECTIVE: This article presents the results of latent profile (cluster) analysis of responses to standardized self-report questionnaires by Canadian military veterans with chronic pain. It identified 5 clusters that appear to represent different drivers of the pain experience. The results could be useful for triaging veterans to the most appropriate pain care providers., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Chronic overlapping pain conditions (COPCs) by definition, frequently co-occur, perhaps reflecting their shared etiologies. Their overlapping nature presents a methodological challenge, possibly masking associations between COPCs and health outcomes attributable to either general or specific processes. To address this challenge, we used population-based cohort data to evaluate the predictive validity of a bifactor model of 9 self-reported COPCs by assessing its association with incident pain-related clinical diagnoses; pain-relevant pharmacotherapy; and other health outcomes. We obtained data from a 2005 to 2006 study of Swedish adult twins linked with health data from nationwide registers through 2016 (N = 25,418). We then fit a bifactor model comprising a general COPC factor and 2 independent specific factors measuring pain-related somatic symptoms and neck and shoulder pain. Accounting for age, biological sex, and cancer, the general factor was associated with increased risk of all pain-related outcomes (eg, COPC diagnosis adjusted odds ratio [aOR], 1.71; 95% confidence interval [1.62, 1.81]), most mental health-related outcomes (eg, depression aOR, 1.72 [1.60, 1.85]), and overdose and mortality (eg, all-cause mortality aOR, 1.25 [1.09, 1.43]). The somatic symptoms specific factor was associated with pain-relevant pharmacotherapy (eg, prescribed opioids aOR, 1.25 [1.15, 1.36]), most mental health-related outcomes (eg, depression aOR, 1.95 [1.70, 2.23]), and overdose (eg, nonfatal overdose aOR, 1.66 [1.31, 2.10]). The neck and shoulder pain-specific factor was weakly and inconsistently associated with the outcomes. Findings provide initial support for the validity and utility of a general-factor model of COPCs as a tool to strengthen understanding of co-occurrence, etiology, and consequences of chronic pain. PERSPECTIVE: This article presents associations between a novel measurement model of COPCs and various health outcomes. Findings provide support for measuring pain across multiple domains rather than only measuring pain specific to one physical location in both research and clinical contexts., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: The management of pain patients has not evolved as rapidly as envisioned when IASP was founded almost 50 years ago. We sought to identify factors that could contribute to this situation, with a focus on concepts of pain and the education of pain physicians., Methods: Relevant literature describing new strategies for diagnosing and managing patients with high-impact chronic pain was reviewed., Results: It appears that the acute-chronic dichotomy has outlived its usefulness and pains should be identified as of peripheral origin or due to central processing errors. Pains of peripheral origin and those of central processing errors require different diagnostic and therapeutic strategies., Discussion: Peripheral treatments and opioids are not effective for central pains. When the cause of the pain lies in the central nervous system, a more centrally focused approach is needed to minimize wasteful pursuit of peripheral causes. The education and training of pain physicians should reflect the skills needed to address these 2 very different clinical problems., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Recruitment for clinical trials and large-scale studies is challenging, especially for patients with complex conditions like chronic pain. Email recruitment has the potential to increase efficiency, to reduce costs, and to improve access for underrepresented patient populations. The objective of this study was to examine the effectiveness, efficiency, and equitability of email versus postal mail recruitment for the Learning to Apply Mindfulness to Pain (LAMP) study, a three-site clinical trial of mindfulness-based interventions for chronic pain., Methods: Patients with chronic pain diagnoses were recruited from three United States Department of Veterans Affairs (VA) facilities using the VA electronic health record (EHR). Recruitment materials were sent using either postal mail (n = 7986) or email (n = 19,333). Patients in the email recruitment group were also mailed introductory postcards before any emails. Mailing addresses and email addresses were obtained from the EHR. Effectiveness was measured by the response rate of patients who logged into the secure LAMP study website. Efficiency was measured by the number of days from when the recruitment materials were sent to when patients logged into the LAMP portal as well as the estimated costs of each recruitment approach. To assess equitability, we examined whether email recruitment was less effective for underrepresented populations, based on demographic information from the EHR., Results: Effectiveness-unadjusted response rates were greater for email versus postal-mail recruitment (18.9% versus 6.3%), and adjusted response rates were over three times greater for email recruitment (RR = 3.5, 95% CI 3.1-3.8) based on a multivariable analysis controlling for age, gender, race, ethnicity, rurality, and site. Efficiency-email recruitment had a significantly lower mean response time (1 day versus 8 days) and a lower cost. Equity-email recruitment led to higher response rates for all subpopulations, including older, non-White, Hispanic, rural, and female Veterans., Conclusions: Email recruitment is an effective, efficient, and equitable way to recruit VA patients to large-scale, chronic pain clinical trials., Trial Registration: Clinical Trial Registration Number: NCT04526158. Patient enrollment began on December 4, 2020., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Thoracic sympathetic ganglion block (TSGB) is a procedure to manage sympathetically maintained upper extremity pain (sympathetically maintained pain). To date, only a few studies have evaluated the clinical effectiveness of TSGB in pain medicine. This study investigated (1) the relationship between technical success of TSGB and pain reduction in patients with chronic upper extremity pain and (2) relevant clinical factors for a positive TSGB outcome., Methods: We retrospectively reviewed medical data in 232 patients who received TSGB from 2004 to 2020. Technical success and a positive outcome of TSGB were defined as a temperature increase of ≥1.5°C at 20 min and a pain reduction with ≥2 points on the 11-point Numerical Rating Scale at 2 weeks post-TSGB, respectively. Correlations were assessed using correlation coefficients (R), and multivariable regression model was used to identify factors relevant to TSGB outcomes., Results: 207 patients were ultimately analyzed; among them, 115 (55.5%) patients positively responded to TSGB, and 139 (67.1%) achieved technical success after TSGB. No significant relationship existed between the pain reduction and the temperature increase after TSGB ( R =0.013, p=0.855). Comorbid diabetes (OR 4.200) and adjuvant intake (OR 3.451) were positively associated, and psychiatric comorbidity (OR 0.327) and pain duration (OR 0.973) were negatively associated with TSGB outcome., Conclusions: We found no significant association between the temperature increase and pain reduction after TSGB. Further studies are warranted to identify significant factors associated with TSGB outcomes in patients with complex regional pain syndrome and neuropathic pain diseases., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic pain is a debilitating and common health issue. General Practitioners (GPs) often prescribe opioids to treat chronic pain, despite limited evidence of benefit and increasing evidence of harms, including prescription Opioid Use Disorder (pOUD). Australian GPs are worried about the harms of long-term opioids, but few are involved in the treatment of pOUD. There is little research on GPs' experiences diagnosing and managing pOUD in their chronic pain patients., Methods: This qualitative research used semi-structured interviews and a case study to investigate GPs' experiences through the lens of the Theory of Planned Behaviour (TPB). TPB describes three factors, an individual's perceived beliefs/attitudes, perceived social norms and perceived behavioural controls. Participants were interviewed via an online video conferencing platform. Interviews were transcribed verbatim and thematically analysed., Results: Twenty-four GPs took part. Participants were aware of the complex presentations for chronic pain patients and concerned about long-term opioid use. Their approach was holistic, but they had limited understanding of pOUD diagnosis and suggested that pOUD had only one treatment: Opioid Agonist Treatment (OAT). Participants felt uncomfortable prescribing opioids and were fearful of difficult, conflictual conversations with patients about the possibility of pOUD. This led to avoidance and negative attitudes towards diagnosing pOUD. There were few positive social norms, few colleagues diagnosed or managed pOUD. Participants reported that their colleagues only offered positive support as this would allow them to avoid managing pOUD themselves, while patients and other staff were often unsupportive. Negative behavioural controls were common with low levels of knowledge, skill, professional supports, inadequate time and remuneration described by many participants. They felt OAT was not core general practice and required specialist management. This dichotomous approach was reflected in their views that the health system only supported treatment for chronic pain or pOUD, not both conditions., Conclusions: Negative beliefs, negative social norms and negative behavioural controls decreased individual behavioural intention for this group of GPs. Diagnosing and managing pOUD in chronic pain patients prescribed opioids was perceived as difficult and unsupported. Interventions to change behaviour must address negative perceptions in order to lead to more positive intentions to engage in the management of pOUD., (© 2024. The Author(s).)

Background: Neck pain is a prevalent global musculoskeletal issue, significantly contributing to the loss of years of healthy life due to disability. Chronic nonspecific neck pain (CNNP) involves diverse symptoms impacting mobility and quality of life. While therapeutic exercises demonstrate efficacy, the role of photobiomodulation therapy (PBMT) remains uncertain. This study aims to assess the additional effects of PBMT within a multimodal therapeutic intervention for CNNP., Methods: A randomized, two-arm, controlled, blind clinical trial follows CONSORT and SPIRIT guidelines. Participants diagnosed with CNNP will receive a stand-alone multimodal therapeutic intervention or the same program with additional PBMT. The primary outcomes will be assessed by the functional disability identified through applying the NDI (Neck Disability Index). Secondary outcomes will be pain intensity during rest and active neck movement, catastrophizing and kinesiophobia, functionality, and disability assessed at baseline, after 8 weeks, and at a 4-week follow-up. Both groups receive pain education before personalized interventions, including resistance exercises, neuromuscular activities, mobility, and body balance. The PBMT group undergoes low-level light therapy. Intention-to-treat analysis, using linear mixed models, employs data presented as mean, standard deviation, and differences with a 95% confidence interval. Non-normally distributed variables transform. Statistical significance is set at 5%., Discussion: This study addresses a critical gap in understanding the combined effects of PBMT and therapeutic exercises for CNNP. The findings aim to guide clinicians, researchers, and CNNP sufferers through rigorous methodology and diverse outcome assessments, offering valuable insights into evidence-based practices for CNNP management. Data confidentiality is maintained throughout, ensuring participant privacy during statistical analysis., Trial Registration: Effects of adding photobiomodulation to a specific therapeutic exercise program for the treatment of individuals with chronic nonspecific neck pain, registration number: NCT05400473, on 2022-05-27., (© 2024. The Author(s).)

Currently-used assessments for fibromyalgia require clinicians to suspect a fibromyalgia diagnosis, a process susceptible to unintentional bias. Automated assessments of standard patient-reported outcomes (PROs) could be used to prompt formal assessments, potentially reducing bias. We sought to determine whether hierarchical clustering of patient-reported pain distribution on digital body map drawings predicted fibromyalgia diagnosis. Using an observational cohort from the University of Pittsburgh's Patient Outcomes Repository for Treatment registry, which contains PROs and electronic medical record data from 21,423 patients (March 17, 2016-June 25, 2019) presenting to pain management clinics, we tested the hypothesis that hierarchical clustering subgroup was associated with fibromyalgia diagnosis, as determined by ICD-10 code. Logistic regression revealed a significant relationship between the body map cluster subgroup and fibromyalgia diagnosis. The cluster subgroup with the most body areas selected was the most likely to receive a diagnosis of fibromyalgia when controlling for age, gender, anxiety, and depression. Despite this, more than two-thirds of patients in this cluster lacked a clinical fibromyalgia diagnosis. In an exploratory analysis to better understand this apparent underdiagnosis, we developed and applied proxies of fibromyalgia diagnostic criteria. We found that proxy diagnoses were more common than ICD-10 diagnoses, which may be due to less frequent clinical fibromyalgia diagnosis in men. Overall, we find evidence of fibromyalgia underdiagnosis, likely due to gender bias. Coupling PROs that take seconds to complete, such as a digital pain body map, with machine learning is a promising strategy to reduce bias in fibromyalgia diagnosis and improve patient outcomes. PERSPECTIVE: This investigation applies hierarchical clustering to patient-reported, digital pain body maps, finding an association between body map responses and clinical fibromyalgia diagnosis. Rapid, computer-assisted interpretation of pain body maps would be clinically useful in prompting more detailed assessments for fibromyalgia, potentially reducing gender bias., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: We investigated differences in somatosensory profiles (SSPs) assessed by quantitative sensory testing in children and adolescents with cerebral palsy (CCP) with and without chronic pain and compared these differences to those in a group of typically developed children and adolescents (TDC) with and without chronic pain., Method: All included subjects were consecutively recruited from and tested at the same outpatient orthopedic clinic by the same investigator. The subjects had their reaction times tested. The SSP consisted of the following tests: warmth (WDT), cool (CDT), mechanical (MDT), and vibration (VDT) detection thresholds; heat (HPT), pressure (PPT), and mechanical (MPT) pain thresholds; wind-up ratio (WUR); dynamic mechanical allodynia (DMA) and cold pressor test (CPT) using a conditioned pain modulation (CPM) paradigm., Results: We included 25 CCP and 26 TDC. TDC without chronic pain served as controls. In TDC with chronic pain, WDT, HPT, HPT intensity, and PPT were higher than in controls. No differences in SSPs between CCP with and without chronic pain were observed. In CCP, the MDT, WDT, CDT, and HPT intensity were higher than in controls. CCP had longer reaction times than TDC. There were no differences regarding the remaining variables., Discussion: In CCP, the SSPs were independent of pain status and findings on MR images. In all CCP the SSPs resembled TDC with chronic pain, compared to TDC without chronic pain. This suggests that CCP do not have the normal neuroplastic adaptive processes that activate and elicit functional changes in the central and peripheral nervous systems., (© 2024 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

The evaluation of chronic pain is challenging because of the lack of specific biomarkers. We identified the Mu opioid receptor-positive (Mu+) B cell percentage of expression, named Mu-Lympho-Marker (MLM), as a candidate marker for chronic pain in fibromyalgia (FM) and osteoarthritis (OA) patients. Here, we investigate the role of MLM on natural killer (NK) cells in the same patients. Twenty-nine FM and twelve OA patients were analyzed, and twenty-three pain-free subjects were considered as the control group. Blood samples were collected to perform immunophenotyping and Western blot analysis. Biological and clinical data were statistically analyzed. The final results showed that the percentage of NK cells expressing Mu was statistically lower in FM and OA patients than in pain-free subjects, as already demonstrated for B cells. A Western blot analysis was performed in order to detect NK cells’ functional status. Moreover, the correlation analysis of MLM expression with pharmacological therapy did not show any significant results. In conclusion, here, we confirm the role of MLM as a suitable marker for chronic pain and underline NK cells as a new possible immune cell type involved in the “Mu opioid receptor reserve theory”.

Complex regional pain syndrome (CRPS) is a debilitating chronic pain condition that, although exceedingly rare, carries a significant burden for the affected patient population. The complex and ambiguous pathophysiology of this condition further complicates clinical management and therapeutic interventions. Furthermore, being a diagnosis of exclusion requires a diligent workup to ensure an accurate diagnosis and subsequent targeted management. The development of the Budapest diagnostic criteria helped to consolidate existing definitions of CRPS but extensive work remains in identifying the underlying pathways. Currently, two distinct types are identified by the presence (CRPS type 1) or absence (CRPS type 2) of neuronal injury. Current management directed at this disease is broad and growing, ranging from non-invasive modalities such as physical and psychological therapy to more invasive techniques such as dorsal root ganglion stimulation and potentially amputation. Ideal therapeutic interventions are multimodal in nature to address the likely multifactorial pathological development of CRPS. Regardless, a significant need remains for continued studies to elucidate the pathways involved in developing CRPS as well as more robust clinical trials for various treatment modalities.

Introduction: The Pain Sensitivity Questionnaire (PSQ) was developed to assess general pain sensitivity., Objective: This study aimed to validate the Greek version of PSQ., Methods: The questionnaire was translated into Greek (PSQ-GR) and piloted in a small sample of patients with chronic pain (n = 35). A total of 146 chronic pain patients and healthy volunteers completed the PSQ-GR, the Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS) and Central Sensitization Inventory (CSI). To evaluate the test-retest reliability, 36 volunteers completed the PSQ-GR twice over 7 ± 2 days., Results: Internal consistency was excellent (Cronbach's alpha 0.90-0.96) for PSQ-total, PSQ-minor, and PSQ-moderate. The Intraclass Correlation Coefficient was estimated at 0.90-0.96 for PSQ-total, PSQ-minor and PSQ-moderate and the SEM was 0.59-0.90 for PSQ-total, PSQ-minor and PSQ-moderate approximately. The smallest detectable change was 0.48 for PSQ-total, 0.47 for PSQ-minor and 0.44 for PSQ-moderate. Positive and significant correlations were observed between PSQ-GR and HADS (r = 0.38, p < 0.01), PCS (r = 0.41, p < 0.01) and CSI (r = 0.30, p < 0.01). Statistically significant differences in PSQ-GR scores were identified between the healthy volunteers and the chronic pain patients., Conclusion: The PSQ-GR is a reliable and valid tool that can assess pain sensitivity in healthy individuals and chronic musculoskeletal pain patients., (© 2024 John Wiley & Sons Ltd.)

Background: The objective of the present study was to evaluate the effect of dexmedetomidine administration during video-assisted thoracoscopic surgery for lung cancer on perioperative inflammatory response and chronic post-surgical pain., Methods: A cohort of 152 patients with lung cancer scheduled for elective video-assisted thoracoscopic surgery participated in this randomized controlled trial. Patients were randomly divided into 2 groups and administered an equivalent volume of dexmedetomidine (n = 63) or normal saline (n = 63). Dexmedetomidine was administered at a dose of 0.6 μg/kg 10 minutes before anesthesia induction and maintained at 0.5 μg/kg/h until 0.5 hours before surgery completed. Anesthesia and postoperative pain management protocols were standardized for both groups. The analysis included vital signs, numerical rating scales of pain, blood inflammatory and oxidative stress biomarkers, pain type and location, patient-controlled intravenous analgesia usage, consumption of general anesthetics and pain rescue medications, as well as complications., Results: The administration of dexmedetomidine resulted in decreased levels of inflammatory cytokines (interleukin-1 beta, interleukin-6, alongside tumor necrosis factor-alpha) and oxidative stress biomarkers (reactive oxygen species alongside malondialdehyde) but elevated levels of interleukin-10 and superoxide dismutase. In addition, the dexmedetomidine group showed lower postoperative numerical rating scale scores, reduced consumption of anesthetics, faster chest-tube removal, fewer patient-controlled intravenous analgesia presses, and shorter postoperative hospital stays., Conclusion: The administration of dexmedetomidine effectively attenuated surgical inflammation, oxidative stress, and postoperative pain, thereby promoting patient recovery after lung cancer surgery without increasing the risk of adverse effects or complications., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose of Review: This paper is an update of the publications on Transitional Pain Services and explores the viability of a dedicated transitional pain service for women., Recent Findings: We address common pain pathologies establishing referral criteria, pathways, and effective strategies to decrease chronification of pain during pregnancy., Summary: This review highlights the importance establishing transitional pain service models at every institution and in particular in obstetric population as pain is normalized by Society during pregnancy., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Consequences of the expanding commercial spaceflight industry include an increase in total number of spaceflight participants and an accompanying surge in the average number of medical comorbidities compared with government-based astronaut corps. A sequela of these developments is an anticipated rise in acute and chronic pain concerns associated with spaceflight. This review will summarize diagnostic and therapeutic areas of interest that can support the comfort of humans in spaceflight., Recent Findings: Painful conditions that occur in space may be due to exposure to numerous stressors such as acceleration and vibration during launch, trauma associated with extravehicular activities, and morbidity resulting directly from weightlessness. Without normal gravitational forces and biomechanical stress, the hostile environment of space causes muscle atrophy, bone demineralization, joint stiffness, and spinal disc dysfunction, resulting in a myriad of pain generators. Repeated insults from abnormal environmental exposures are thought to contribute to the development of painful musculoskeletal and neuropathic conditions., Summary: As humanity invests in Lunar and Martian exploration, understanding the painful conditions that will impede crew productivity and mission outcomes is critical. Preexisting pain and new-onset acute or chronic pain resulting from spaceflight will require countermeasures and treatments to mitigate long-term health effects., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Study Objective: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by the congenital absence of the uterus and vagina, sometimes with associated extragenital anomalies. Currently, there is limited literature on pelvic pain and comorbid pain syndromes in people with MRKH. The aims of this scoping review were to summarize existing literature on pelvic and generalized persistent pain syndromes associated with MRKH and to identify knowledge gaps for further research into this field., Methods: This scoping review followed the Joanna Briggs Institute framework. The population of interest was patients with a diagnosis of MRKH. MEDLINE, CINAHL, Scopus, Cochrane, Embase, and Emcare databases were searched. Articles that did not meet the inclusion criteria or critical appraisal standards were excluded. The resultant articles were reviewed by 2 independent researchers, and a third was used in cases of disagreement. A descriptive analytical method was used for data analysis., Results: We screened 3348 articles for eligibility. Of these, 39 articles, which described 1353 cases of MRKH, met the criteria. Four studies described baseline pelvic pain in MRKH, 19 described acute presentations, and 13 described postintervention pain levels., Conclusion: Despite the paucity of research, this review found that cyclic pelvic pain was mostly present in women with uterine remnants, whereas pelvic pain in those without remnants was poorly understood. There were no studies exploring generalized persistent pain syndromes in MRKH. Further cross-sectional studies are needed to elucidate the prevalence and levels of pain syndromes in MRKH., Competing Interests: Conflicts of interest RUG, CP, and IW have no potential conflicts to disclose. SRG is a consultant obstetrician and gynecologist and pain medicine specialist at The Royal Children's Hospital, Melbourne. ND is a consultant obstetrician and gynecologist at Cairns Hospital., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: It is estimated that approximately a third of patients undergoing certain surgeries may report some degree of persistent pain postoperatively. Chronic postsurgical pain (CPSP) reduces quality of life, is challenging to treat, and has significant socio-economic impact., Recent Findings: From an epidemiological perspective, factors that predispose patients to the development of CPSP may be considered in relation to the patient, the procedure or, the care environment. Prevention or management of transition from acute to chronic pain often need a multidisciplinary approach beginning early in the preoperative period and continuing beyond surgical admission. The current concepts regarding the role of central and peripheral nervous systems in chronification of pain may provide targets for future therapies but, the current evidence seems to suggest that a multimodal analgesic approach of preventive analgesia along with a continued follow-up and treatment after hospital discharge may hold the key to identify and manage the transitioning of acute to chronic pain., Summary: A comprehensive multidisciplinary approach with prior identification of risk factors, minimizing the surgical insult and a culture of utilizing multimodal analgesia and continued surveillance beyond the period of hospitalization is an important step towards reducing the development of chronic pain. A transitional pain service model may accomplish many of these goals., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Joint hypermobility syndromes, particularly chronic pain associated with this condition, including Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders (HSD), present diagnostic challenges due to their multifactorial origins and remain poorly understood from biomechanical and genomic-molecular perspectives. Recent diagnostic guidelines have differentiated hEDS, HSD, and benign joint hypermobility, providing a more objective diagnostic framework. However, incorrect diagnoses and underdiagnoses persist, leading to prolonged journeys for affected individuals. Musculoskeletal manifestations, chronic pain, dysautonomia, and gastrointestinal symptoms illustrate the multifactorial impact of these conditions, affecting both the physical and emotional well-being of affected individuals. Infrared thermography (IRT) emerges as a promising tool for joint assessment, especially in detecting inflammatory processes. Thermal distribution patterns offer valuable insights into joint dysfunctions, although the direct correlation between pain and inflammation remains challenging. The prevalence of neuropathies among hypermobile individuals accentuates the discordance between pain perception and thermographic findings, further complicating diagnosis and management. Despite its potential, the clinical integration of IRT faces challenges, with conflicting evidence hindering its adoption. However, studies demonstrate objective temperature disparities between healthy and diseased joints, especially under dynamic thermography, suggesting its potential utility in clinical practice. Future research focused on refining diagnostic criteria and elucidating the underlying mechanisms of hypermobility syndromes will be essential to improve diagnostic accuracy and enhance patient care in this complex and multidimensional context., (Copyright ©2024, Yale Journal of Biology and Medicine.)

Background: Fibromyalgia (FM) is a complex disorder with widespread pain and emotional distress, posing diagnostic challenges. FM patients show altered cognitive and emotional processing, with a preferential allocation of attention to pain-related information. This attentional bias towards pain cues can impair cognitive functions such as inhibitory control, affecting patients' ability to manage and express emotions. Sentiment analysis using large language models (LLMs) can provide insights by detecting nuances in pain expression. This study investigated whether open-source LLM-driven sentiment analysis could aid FM diagnosis., Methods: 40 patients with FM, according to the 2016 American College of Rheumatology Criteria and 40 non-FM chronic pain controls referred to rheumatology clinics, were enrolled. Transcribed responses to questions on pain and sleep were machine translated to English and analysed by the LLM Mistral-7B-Instruct-v0.2 using prompt engineering targeting FM-associated language nuances for pain expression ('prompt-engineered') or an approach without this targeting ('ablated'). Accuracy, precision, recall, specificity and area under the receiver operating characteristic curve (AUROC) were calculated using rheumatologist diagnosis as ground truth., Results: The prompt-engineered approach demonstrated accuracy of 0.87, precision of 0.92, recall of 0.84, specificity of 0.82 and AUROC of 0.86 for distinguishing FM. In comparison, the ablated approach had an accuracy of 0.76, precision of 0.75, recall of 0.77, specificity of 0.75 and AUROC of 0.76. The accuracy was superior to the ablated approach (McNemar's test p<0.001)., Conclusion: This proof-of-concept study suggests LLM-driven sentiment analysis, especially with prompt engineering, may facilitate FM diagnosis by detecting subtle differences in pain expression. Further validation is warranted, particularly the inclusion of secondary FM patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic low back pain (CLBP) is a frequent disease. It is a critical health concern that can influence functional capacity by restricting living activities., Objectives: The current study is to investigate the effects of transcutaneous vagus nerve stimulation (TVNs) in the management of CLBP., Methods: We searched the databases on Google Scholar, PubMed, Web of Science, Cochrane, and Pedro for randomized clinical trial (RCT) studies published in any language that looked at the effectiveness of TVNs in people with chronic LBP. The inclusion criteria were PICO. Participants in the research were people (≥ 18 years) diagnosed with persistent low back pain for more than 3 months. Study quality was assessed using Cochrane ROB 2., Results: Our database search found 1084 RCT. A number of studies that were not necessary for the issue were removed, and the overall outcome was six trials. Risk of bias (ROB) evaluations at the study level (derived from outcomes) are reported. In the six studies, two (33.3%) had an overall uncertain ROB (i.e., some concerns), whereas one (16.7%) had a high overall ROB. Three trials (50%) had a low overall RoB., Conclusion: There is still no evidence to support the use of transcutaneous vagus nerve stimulation as a viable therapeutic rehabilitation strategy. Therefore, we recommend high-quality trials and long-term follow-up to evaluate disability, quality of life, and pain outcomes in these patients., (© 2024. The Author(s).)

Objective: To explore and characterize somatosensory dysfunction in patients with post-polio syndrome and chronic pain, by conducting examinations with Quantitative Sensory Testing., Design: A cross-sectional, descriptive, pilot study conducted during 1 month., Subjects/patients: Six patients with previously established post-polio syndrome and related chronic pain., Methods: All subjects underwent a neurological examination including neuromuscular function, bedside sensory testing, a thorough pain anamnesis, and pain drawing. Screening for neuropathic pain was done with 2 questionnaires. A comprehensive Quantitative Sensory Testing battery was conducted with z-score transformation of obtained data, enabling comparison with published reference values and the creation of sensory profiles, as well as comparison between the study site (more polio affected extremity) and internal control site (less affected extremity) for each patient., Results: Derived sensory profiles showed signs of increased prevalence of sensory aberrations compared with reference values, especially Mechanical Pain Thresholds, with significant deviation from reference data in 5 out of 6 patients. No obvious differences in sensory functions were seen between study sites and internal control sites., Conclusion: Post-polio syndrome may be correlated with a mechanical hyperalgesia/allodynia and might be correlated to a somatosensory dysfunction. With lack of evident side-to-side differences, the possibility of a generalized dysfunction in the somatosensory system might be considered.

Exercise is a front-line intervention to increase functional capacity and reduce pain and disability in people with low strength levels or disorders. However, there is a lack of validated field-based tests to check the initial status and, more importantly, to control the process and make tailored adjustments in load, intensity, and recovery. We aimed to determine the test-retest reliability of a submaximal, resistance-band test to evaluate the strength of the trunk stability muscles using a portable force sensor in middle-aged adults (48 ± 13 years) with medically diagnosed chronic low back pain and healthy peers ( n = 35). Participants completed two submaximal progressive tests of two resistance-band exercises (unilateral row and Pallof press), consisting of 5 s maintained contraction, progressively increasing the load. The test stopped when deviation from the initial position by compensation movements occurred. Trunk muscle strength (CORE muscles) was monitored in real time using a portable force sensor (strain gauge). Results revealed that both tests were highly reliable (intra-class correlation [ICC] > 0.901) and presented low errors and coefficients of variation (CV) in both groups. In particular, people with low back pain had errors of 14-19 N (CV = 9-12%) in the unilateral row test and 13-19 N (CV = 8-12%) in the Pallof press. No discomfort or pain was reported during or after the tests. These two easy-to-use and technology-based tests result in a reliable and objective screening tool to evaluate the strength and trunk stability in middle-aged adults with chronic low back pain, considering an error of measurement < 20 N. This contribution may have an impact on improving the individualization and control of rehabilitation or physical training in people with lumbar injuries or disorders.

Background: The disability and significant economic costs accredited to Low back pain (LBP) are likely to rise which is an essential problem in low and middle-income countries like Pakistan. The associated factors of LBP are age, sex, and race including physical activity, high spinal load, lifting, bending, and twisting occupations. The literature highlighted there is substantial differences in associated factors of LBP within available studies in developing countries. The objective is to investigate the association of demographic factors and lumbar range of motion with disability in patients with chronic low back., Methods: A baseline data analysis was performed as an analytical cross-sectional study among 150 patients with chronic low back in a randomized controlled trial with a duration from March 2020 and January 2021. After recording demographics, Modified-Modified Schober's test was used to measure lumbar flexion and extension and Oswestry disability index for disability. After the descriptive analysis the continuous variables, age and pain were analyzed with Spearman's correlation. Variables that were significant in bivariate analysis were then fitted in a multivariable linear regression. The Kruskal-Wallis test was used to analyze variations of disability in gender, marital status, work status, education level, and duration of pain. The p-value of 0.05 was significant., Results: The results showed a significant correlation between age and pain in sitting (rh=-0.189, p = 0.021 and rh = 0.788, p < 0.001) with the disability but no significant effects of age and pain in sitting (B=-0.124, p = 0.212 and B = 1.128, p = 0.082) on disability were found. The decrease in lumbar flexion and extension was found to increase disability (B=-6.018 and - 4.032 respectively with p < 0.001). Female gender (x2(1) = 15.477, p = < 0.001) and unmarried marital status (x2(1) = 4.539, p = 0.033) had more disability than male gender and married marital status, respectively. There was a significance between groups of the duration of pain regarding disability (x2 (2) = 70.905, p < 0.001). Age, education level, and work status showed no significance (p > 0.05)., Conclusions: The female gender and unmarried marital status are associated with functional disability. Decreased lumbar range of motion accompanies more disability, while age, education level, and work status do not effect on disability., (© 2024. The Author(s).)

Objective: The present pilot study aimed to propose an innovative scale-independent measure based on electroencephalographic (EEG) signals for the identification and quantification of the magnitude of chronic pain., Methods: EEG data were collected from three groups of participants at rest: seven healthy participants with pain, 15 healthy participants submitted to thermal pain, and 66 participants living with chronic pain. Every 30 s, the pain intensity score felt by the participant was also recorded. Electrodes positioned in the contralateral motor region were of interest. After EEG preprocessing, a complex analytical signal was obtained using Hilbert transform, and the upper envelope of the EEG signal was extracted. The average coefficient of variation of the upper envelope of the signal was then calculated for the beta (13-30 Hz) band and proposed as a new EEG-based indicator, namely Piq β , to identify and quantify pain., Main Results: The main results are as follows: (1) A Piq β threshold at 10%, that is, Piq β ≥ 10%, indicates the presence of pain, and (2) the higher the Piq β (%), the higher the extent of pain., Conclusions: This finding indicates that Piq β can objectively identify and quantify pain in a population living with chronic pain. This new EEG-based indicator can be used for objective pain assessment based on the neurophysiological body response to pain., Significance: Objective pain assessment is a valuable decision-making aid and an important contribution to pain management and monitoring.

Background: Despite recent improvements in cancer detection and survival rates, managing cancer-related pain remains a significant challenge. Compared to neuropathic and inflammatory pain conditions, cancer pain mechanisms are poorly understood, despite pain being one of the most feared symptoms by cancer patients and significantly impairing their quality of life, daily activities, and social interactions. The objective of this work was to select a panel of biomarkers of central pain processing and modulation and assess their ability to predict chronic pain in patients with cancer using predictive artificial intelligence (AI) algorithms., Methods: We will perform a prospective longitudinal cohort, multicentric study involving 450 patients with a recent cancer diagnosis. These patients will undergo an in-person assessment at three different time points: pretreatment, 6 months, and 12 months after the first visit. All patients will be assessed through demographic and clinical questionnaires and self-report measures, quantitative sensory testing (QST), and electroencephalography (EEG) evaluations. We will select the variables that best predict the future occurrence of pain using a comprehensive approach that includes clinical, psychosocial, and neurophysiological variables., Discussion: This study aimed to provide evidence regarding the links between poor pain modulation mechanisms at precancer treatment in patients who will later develop chronic pain and to clarify the role of treatment modality (modulated by age, sex and type of cancer) on pain. As a final output, we expect to develop a predictive tool based on AI that can contribute to the anticipation of the future occurrence of pain and help in therapeutic decision making., (© 2024. The Author(s).)

Background: Understanding the association of acute pain intensity and opioid consumption after cardiac surgery with chronic postsurgical pain (CPSP) can facilitate implementation of personalized prevention measures to improve outcomes. The objectives were to (1) examine acute pain intensity and daily mg morphine equivalent dose (MME/day) trajectories after cardiac surgery, (2) identify factors associated with pain intensity and opioid consumption trajectories, and (3) assess whether pain intensity and opioid consumption trajectories are risk factors for CPSP., Methods: Prospective observational cohort study design conducted between August 2012 and June 2020 with 1-year follow-up. A total of 1115 adults undergoing cardiac surgery were recruited from the preoperative clinic. Of the 959 participants included in the analyses, 573 completed the 1-year follow-up. Main outcomes were pain intensity scores and MME/day consumption over the first 6 postoperative days (PODs) analyzed using latent growth mixture modeling (GMM). Secondary outcome was 12-month CPSP status., Results: Participants were mostly male (76%), with a mean age of 61 ± 13 years. Three distinct linear acute postoperative pain intensity trajectories were identified: "initially moderate pain intensity remaining moderate" (n = 62), "initially mild pain intensity remaining mild" (n = 221), and "initially moderate pain intensity decreasing to mild" (n = 251). Age, sex, emotional distress in response to bodily sensations, and sensitivity to pain traumatization were significantly associated with pain intensity trajectories. Three distinct opioid consumption trajectories were identified on the log MME/day: "initially high level of MME/day gradually decreasing" (n = 89), "initially low level of MME/day remaining low" (n = 108), and "initially moderate level of MME/day decreasing to low" (n = 329). Age and emotional distress in response to bodily sensations were associated with trajectory membership. Individuals in the "initially mild pain intensity remaining mild" trajectory were less likely than those in the "initially moderate pain intensity remaining moderate" trajectory to report CPSP (odds ratio [95% confidence interval, CI], 0.23 [0.06-0.88]). No significant associations were observed between opioid consumption trajectory membership and CPSP status (odds ratio [95% CI], 0.84 [0.28-2.54] and 0.95 [0.22-4.13])., Conclusions: Those with moderate pain intensity right after surgery are more likely to develop CPSP suggesting that those patients should be flagged early on in their postoperative recovery to attempt to alter their trajectory and prevent CPSP. Emotional distress in response to bodily sensations is the only consistent modifiable factor associated with both pain and opioid trajectories., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Purpose of Review: To provide an updated summary on the epidemiology, pathophysiology, and treatment strategies of chronic pain in pediatric patients and its differences with chronic pain in adults., Recent Findings: Chronic pain in children is common, can be debilitating and can progress into adulthood, thus it requires an interdisciplinary evaluation and management. Targeting interdisciplinary care, including psychology, physical, and/or occupational therapy, has been shown to improve pain and function. Recent decline in mental health post pandemic has correlated with increase in pediatric chronic pain thus the need to identify patients at risk and offer early interdisciplinary treatment., Summary: Chronic pediatric pain should be addressed under the biopsychosocial model, where the biological, psychological, and social factors are evaluated on how they influence the pain perception, pain experience, functional ability, and treatment focus. Pain education to patients and their families is the crucial initial step towards a functional rehabilitation of pain., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Central sensitivity (CS) is defined as an increased responsiveness of nociceptive neurons in the central nervous system to normal or subthreshold inputs. CS has recently been linked to the psychological burden associated with chronic pain, such as fibromyalgia (FM). The primary objective of this study is to investigate the impact of specific psychological constructs on CS in patients with FM. In Study 1, we explore the influence of temperament, personality, childhood trauma, defence mechanisms, and mental pain on CS. In Study 2, our goal is to test the role of the best predictors of CS in influencing quality of life (QoL) and FM functioning through a path analysis model., Methods: A total of 510 women with FM participated online, completing a self-administered protocol. Data collection took place between April and June of 2023., Results: In Study 1, higher levels of low sensory threshold (β=0.210), traumatic experiences of physical threat (β=0.141), neurotic defences (β=0.124), and mental pain (β=0.241) emerged as the strongest predictors of increased CS. In Study 2, the presented model demonstrated a satisfactory fit (chi2=27.200; df=10; p=0.002; GFI=0.984; NFI=0.949; CFI=0.967; RMSEA=0.061 [95% CI 0.034-0.090]) with large and medium effect sizes on physical (-0.576) and psychological (-0.190) QoL., Conclusions: The study underscores the pivotal role of psychological dimensions in influencing CS levels and their relationships with QoL in patients with FM.

Based on the presence of chronic pain and the potential use of common treatment agents in Notalgia Paresthetica (NP) and Fibromyalgia Syndrome (FMS) for improvement, we aimed to investigate the frequency of FMS symptoms in NP patients and its impact on quality of life. This study is a case control cohort study including 26 patients diagnosed with NP and a total of 26 controls matched for age and gender. The 2016 revised fibromyalgia diagnostic criteria by the American College of Rheumatology (ACR) were used to inquire about FMS diagnosis criteria in the study. According to the 2016 ACR revised FMS diagnostic criteria, the frequency of FMS was significantly higher in the patient group (n = 9, 34.6%) compared to the control group (n = 2, 7.7%) (p = 0.042). The Wide Pain Index (WPI) score in the control group was 2.00 (3.25), while in the patient group, it was 4.00 (8.00), with a statistically significant difference between them (p < 0.035). Furthermore, significant statistical differences were found between the two groups in terms of Symptom Severity Scale (SSS), Fibromyalgia Score (FS), and FIQ (p < 0.035, p < 0.001, p < 0.001, respectively). In NP patients with accompanying FMS, Dermatology Life Quality Index was significantly more affected compared to those without FMS (p = 0.025). In conclusion, we recommend that NP patients be questioned about FMS, which is characterized by generalized pain, as well as regional neuropathic symptoms. Treatment success can be enhanced by using common agents in the treatment choice for accompanying FMS., (© 2024. The Author(s).)

Chronic nonbacterial osteitis (CNO) is a rare musculoskeletal disease causing chronic bone pain. It is known that chronic musculoskeletal pain may involve other mechanisms than nociceptive pain only. We investigate the prevalence of neuropathic and nociplastic pain in adult CNO and their association with clinical characteristics and treatment outcomes. Survey study among the Dutch adult CNO cohort (n = 84/195 participated), including PAIN-detect for neuropathic pain, and the Central Sensitization Inventory (CSI), Fibromyalgia Rapid Screening Tool (FiRST), and ACTTION-APS Pain Taxonomy (AAPT) for nociplastic pain. Clinical characteristics and CNO-related bone pain scores were compared between patients with exclusive nociceptive pain and those with nociceptive pain plus neuropathic and/or nociplastic pain (mixed pain). 31% (95% CI 21-41) of patients classified as likely having neuropathic pain according to PAIN-detect. 53% (41-64) of patients displayed central sensitization on CSI, 61% (50-72) screened positive for fibromyalgia on FiRST and 14% (7-23) of patients fulfilled the AAPT criteria, all indicative of nociplastic pain. Mixed pain was associated with longer diagnostic delay (mean difference 2.8 years, 95% CI 0.4-5.2, p = 0.023), lower educational level (72% versus 20%, p < 0.001), and opioid use (37% versus 13%, p = 0.036). Despite comparable disease severity and extent, patients with mixed pain reported significantly higher CNO-related bone pain scores. This study demonstrates the high prevalence of mixed pain in adult CNO, in which neuropathic and nociplastic pain exist alongside nociceptive inflammatory bone pain. Disease burden in CNO may extend beyond inflammatory activity, highlighting the need for a multifaceted management approach., (© 2024. The Author(s).)