Brain-derived neurotrophic factor (BDNF) in chronic pain research: A decade of bibliometric analysis and network visualization.

Chronic pain research, with a specific focus on the brain-derived neurotrophic factor (BDNF), has made impressive progress in the past decade, as evident in the improved research quality and increased publications. To better understand this evolving landscape, a quantitative approach is needed. The main aim of this study is to identify the hotspots and trends of BDNF in chronic pain research. We screened relevant publications from 2013 to 2022 in the Scopus database using specific search subject terms. A total of 401 documents were selected for further analysis. We utilized several tools, including Microsoft Excel, Harzing's Publish or Perish, and VOSViewer, to perform a frequency analysis, citation metrics, and visualization, respectively. Key indicators that were examined included publication growth, keyword analyses, topmost influential articles and journals, networking by countries and co-citation of cited references. Notably, there was a persistent publication growth between 2015 and 2021. "Neuropathic pain" emerged as a prominent keyword in 2018, alongside "microglia" and "depression". The journal Pain® was the most impactful journal that published BDNF and chronic pain research, while the most influential publications came from open-access reviews and original articles. China was the leading contributor, followed by the United States (US), and maintained a leadership position in the total number of publications and collaborations. In conclusion, this study provides a comprehensive list of the most influential publications on BDNF in chronic pain research, thereby aiding in the understanding of academic concerns, research hotspots, and global trends in this specialized field.

The sex-dependent impact of adipose tissue and inflammation on chronic pain - A cross-sectional study from the all of us research program.

Emerging evidence suggests an association between chronic pain and elevated body fat. We sought to determine if individuals with higher body fat, measured by hip circumference (HC) and waist circumference (WC), are at risk for chronic pain when they demonstrate higher expression of inflammatory markers. We investigated the incidence and severity of pain in patients with varying WC/HC and inflammatory markers (C-Reactive Protein, IL-6, leptin) using the NIH-sponsored All of Us Database. For each inflammatory marker and sex, participants were divided into four groups based on combinations of normal/high marker levels and small/large WC/HC. We used statistical analysis to compare WC/HC and pain severity (mean NRS pain score) between groups of the same sex. In females, but not males, combinations of elevated CRP with large WC/HC exerted additive effects on the incidence of chronic pain (p < 0.01) and severe pain (p < 0.001), as well as on the severity of pain evaluated by the mean NRS pain score (p < 0.01). This relationship held true for females with high IL-6 or leptin and large WC or HC (p < 0.001 for chronic pain and severe pain incidence, and p < 0.05 for pain severity). Neither IL-6 nor leptin showed any significant impact on pain in males. Obesity status and CRP exert additive prognostic effects for chronic pain in females, but not in males. The concomitant evaluation of other inflammatory factors, such as IL-6 or leptin in females, may further augment the prediction of chronic pain. PERSPECTIVE: This article investigates the relationship between chronic pain, obesity, and inflammatory markers. It could help elucidating sex difference in pain mechanisms, as well as the risk factors for chronic pain, potentially improving patient diagnosis, follow-up and treatment.

Distinct Functional Connectivity Patterns for Intermittent Vs Constant Neuropathic Pain Phenotypes in Persistent Spinal Pain Syndrome Type 2 Patients.

Background: Chronic low back pain (cLBP) has been associated with alterations in brain functional connectivity (FC) but based upon heterogeneous populations and single network analyses. Our goal is to study a more homogeneous cLBP population and focus on multiple cross-network (CN) connectivity analysis. We hypothesize that within this population: 1) altered CN FC, involving emotion and reward/aversion functions are related to their pain levels and 2) altered relationships are dependent upon pain phenotype (constant neuropathic vs intermittent pain). Methods: In this case series, resting state fcMRI scans were obtained over a study duration of 60 months from 23 patients (13 constant neuropathic and 10 intermittent pain) with Persistent Spinal Pain Syndrome (PSPS Type 2) being considered for spinal cord stimulation (SCS) therapy at a single academic center. Images were acquired using a Discovery MR750 GE scanner. During the resting state acquisitions, they were asked to close their eyes and relax. The CN analysis was performed on 7 brain networks and compared to age-matched controls. Linear regression was used to test the correlation between CN connectivity and pain scores. Results: CN FC involving emotion networks (STM: striatum network index) was significantly lower than controls in all patients, regardless of pain phenotype (P < 0.003). Pain levels were positively correlated with emotional FC for intermittent pain but negatively correlated for constant pain. Conclusion: This is the first report of 1) altered CN FC involving emotion/reward brain circuitry in 2) a homogeneous population of cLBP patients with 3) two different pain phenotypes (constant vs intermittent) in PSPS Type 2 patients being considered for SCS. FC patterns were altered in cLBP patients as compared to controls and were characteristic for each pain phenotype. These data support fcMRI as a potential and objective tool in assessing pain levels in cLBP patients with different pain phenotypes.

Designing a primary care pharmacist-led review for people treated with opioids for persistent pain: a multi-method qualitative study.

BACKGROUND: Opioids are frequently prescribed for persistent non-cancer pain despite limited evidence of long-term effectiveness and risk of harm. Evidence-based interventions to address inappropriate opioid prescribing are lacking. AIM: To explore perspectives of people living with persistent pain to understand barriers and facilitators in reducing opioids in the context of a pharmacist-led primary care review, and identify review components and features for optimal delivery. DESIGN & SETTING: Primary care multi-method qualitative study. METHOD: Adults with experience of persistent pain and taking opioids participated in semi-structured interviews (n=15, 73% female) and an online discussion forum (n=31). The Theoretical Domains Framework (TDF) provided a framework for data collection and thematic analysis, involving deductive analysis to TDF domains, inductive analysis within-domains to generate subthemes, and subtheme comparison to form across-domain overarching themes. The behaviour change technique taxonomy v.1 and motivational behaviour change technique classification system were used to systematically map themes to behaviour change techniques to identify potential review components and delivery features. RESULTS: 32 facilitator and barrier subthemes for patients reducing opioids were identified across 13 TDF domains. These combined into six overarching themes: learning to live with pain, opioid reduction expectations, assuming a medical model, pharmacist-delivered reviews, pharmacist-patient relationship and patient engagement. Subthemes mapped to 21 unique behaviour change techniques, yielding 17 components and five delivery features for the proposed PROMPPT review. CONCLUSION: This study generated theoretically-informed evidence for design of a practice pharmacist-led PROMPPT review. Future research will test the feasibility and acceptability of the PROMPPT review and pharmacist training.

Update on Musculoskeletal Pain Management.

Pain is the most common complaint reported to orthopedists in the outpatient clinic, emergency room, or booth. Numerous publications report the inadequate management of both acute and chronic pain by health professionals. This updated article aims to provide information about musculoskeletal pain, its classification, evaluation, diagnosis, and the multimodal therapeutic approach for each case. For acute pain, adequate control allows for earlier rehabilitation to work and reduces the rates of pain chronification. For chronic pain, the goal is to reduce its intensity and improve the quality of life. Currently, some procedures are increasingly used and aided by imaging tests for diagnostic and therapeutic purposes.

Latent Profile Analysis of Canadian Military Veterans with Chronic Pain Identifies 5 Meaningful Classes through Self-Report Measures.

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 seven potential drivers of the pain experience. Maximum Likelihood-based Latent Profile Analysis (MLE-LPA) was used to identify clinically and statistically meaningful profiles using the seven-axis variables, and Classification and Regression Tree (CART) 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 MLE-LPA 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 healthcare 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.

Claustrum projections to the anterior cingulate modulate nociceptive and pain-associated behavior.

The anterior cingulate cortex (ACC) is critical for the perception and unpleasantness of pain.1,2,3,4,5,6 It receives nociceptive information from regions such as the thalamus and amygdala and projects to several cortical and subcortical regions of the pain neuromatrix.7,8 ACC hyperexcitability is one of many functional changes associated with chronic pain, and experimental activation of ACC pyramidal cells produces hypersensitivity to innocuous stimuli (i.e., allodynia).9,10,11,12,13,14 A less-well-studied projection to the ACC arises from a small forebrain region, the claustrum.15,16,17,18,19,20 Stimulation of excitatory claustrum projection neurons preferentially activates GABAergic interneurons, generating feed-forward inhibition onto excitatory cortical networks.21,22,23,24 Previous work has shown that claustrocingulate projections display altered activity in prolonged pain25,26,27; however, it remains unclear whether and how the claustrum participates in nociceptive processing and high-order pain behaviors. Inhibition of ACC activity reverses mechanical allodynia in animal models of persistent and neuropathic pain,1,9,28 suggesting claustrum inputs may function to attenuate pain processing. In this study, we sought to define claustrum function in acute and chronic pain. We found enhanced claustrum activity after a painful stimulus that was attenuated in chronic inflammatory pain. Selective inhibition of claustrocingulate projection neurons enhanced acute nociception but blocked pain learning. Inversely, chemogenetic activation of claustrocingulate neurons had no effect on basal nociception but rescued inflammation-induced mechanical allodynia. Together, these results suggest that claustrocingulate neurons are a critical component of the pain neuromatrix, and dysregulation of this connection may contribute to chronic pain.

Partners' Experiences of Chronic Pain: A Qualitative Evidence Synthesis.

This systematic review of qualitative studies synthesised evidence on the experience chronic pain from the perspective of romantic partners. Medline via Ovid, Embase via Ovid, CINAHL via EBSCO, APA PsycInfo via Ovid, Scopus, and Web of Science databases were searched. Studies exploring the impact of chronic pain from partners' perspectives using qualitative data collection methods were eligible for inclusion. Thematic synthesis was conducted, and confidence in the review findings was assessed using GRADE CERQual criteria. A total of 198 participants were represented from 15 primary studies. Four interconnected analytical themes were developed: 'life is different', 'internal conflict between two worlds', 'togetherness vs separateness', and 'coping in the longer term'. Out of 27 review findings, 9 were assessed as high confidence, 12 as moderate confidence, 4 as low confidence, and 2 as very low confidence. Socially isolated partners, those in strained relationships, and partners who continually sacrificed their own needs were more likely to experience distressing emotions. Greater recognition of partners' needs is needed within pain management services.

Ultramicronized N-palmitoylethanolamine associated with analgesics: Effects against persistent pain.

Current epidemiological data estimate that one in five people suffers from chronic pain with considerable impairment of health-related quality of life. The pharmacological treatment is based on first- and second-line analgesic drugs, including COX-2 selective and nonselective nonsteroidal anti-inflammatory drugs, paracetamol, antidepressants, anti-seizure drugs and opioids, that are characterized by important side effects. N-palmitoylethanolamine (PEA) is a body's own fatty-acid ethanolamide belonging to the family of autacoid local injury antagonist amides. The anti-inflammatory and pain-relieving properties of PEA have been recognized for decades and prompted to depict its role in the endogenous mechanisms of pain control. Together with its relative abundance in food sources, this opened the way to the use of PEA as a pain-relieving nutritional intervention. Naïve PEA is a large particle size lipid molecule with low solubility and bioavailability. Reducing particle size is a useful method to increase surface area, thereby improving dissolution rate and bioavailability accordingly. Micron-size formulations of PEA (e.g., ultramicronized and co-(ultra)micronized) have shown higher oral efficacy compared to naïve PEA. In particular, ultramicronized PEA has been shown to efficiently cross the intestinal wall and, more importantly, the blood-brain and blood-spinal cord barrier. Several preclinical and clinical studies have shown the efficacy, safety and tolerability of ultramicronized PEA. This narrative review summarizes the available pharmacokinetic/pharmacodynamic data on ultramicronized PEA and focuses to its contribution to pain control, in particular as 'add-on' nutritional intervention. Data showing the ability of ultramicronized PEA to limit opioid side effects, including the development of tolerance, have also been reviewed.

Peer victimization, posttraumatic stress symptoms, and chronic pain: A longitudinal examination.

Chronic pain and posttraumatic stress disorder symptoms (PTSS) co-occur at high rates in youth and are linked to worse pain outcomes and quality of life. While peer victimization has been posited as a mechanism underlying the PTSS-pain relationship in youth, empirical evidence suggests that it may exacerbate both PTSS and pain. The present study aimed to longitudinally examine PTSS as a mediator in the relationship between peer victimization at baseline and pain-related outcomes at 3 months in youth with chronic pain. Participants included 182 youth aged 10-18 years recruited from a tertiary level children's hospital in Western Canada. At baseline, participants completed measures to assess pain (intensity and interference), peer victimization (relational and overt), and PTSS. Pain was re-assessed at 3-month follow-up. Primary hypotheses were tested utilizing a series of mediation analyses with PTSS as a proposed mediator in the associations between peer victimization and pain outcomes. Youth PTSS mediated the relationship between higher baseline relational victimization and higher 3-month pain interference, while controlling for baseline pain interference. Three-month pain intensity was not correlated with peer victimization; thus, pain intensity was not included in analyses. These findings reveal that PTSS may be an underlying factor in the co-occurrence of peer victimization and chronic pain in youth. Further research is needed to better understand the role of peer victimization in the maintenance of chronic pain to ensure appropriate, effective, and timely interventions that address the social and mental health issues impacting the lives of these youth as well as their pain. PERSPECTIVE: PTSS may be an underlying factor in the co-occurrence between peer victimization and chronic pain in youth, highlighting the need to assess for both peer relationship problems and PTSS in youth with chronic pain.

Impact of Shared Decision-Making on Opioid Prescribing Among Patients with Chronic Pain: A Retrospective Cohort Study.

Shared decision-making (SDM) involving patient and physician is a desirable goal that is recommended in chronic pain management guidelines. This study measured whether SDM affects opioid prescribing frequency for chronic low back pain. A retrospective cohort study involving 1478 participants was conducted within a national pain research registry. The patient participation and patient orientation (PPPO) scale of the Communication Behavior Questionnaire was used to measure SDM, including classification of greater SDM (PPPO scale score≥80) or lesser SDM (PPPO scale score<80). Opioid prescribing frequency was measured at quarterly intervals from enrollment through 12 months. Baseline and longitudinal covariates were collected to adjust for potential confounding using generalized estimating equations. The mean age of participants was 53.1 (SD, 13.2) years and 1098 (74.3%) were female. A total of 473 (32.0%) participants were prescribed opioids at baseline. Participants completed 5968 encounters wherein multivariable analyses demonstrated that PPPO scale scores were associated with more frequent opioid prescribing (ß=0.013; 95% CI, 0.005 to 0.021; P<0.001). Greater SDM was associated with more frequent opioid prescribing than lesser SDM (ß=0.441; 95% CI, 0.160 to 0.722; P=0.002). Opioids were prescribed in 34.3% vs. 25.2% of encounters with greater vs. lesser SDM (OR, 1.55; 95% CI, 1.17-2.06). SDM remained associated with more frequent opioid prescribing in a series of sensitivity analyses. Although SDM is desirable in chronic pain management, complex issues and challenging patient conversations may arise during serial assessments of the appropriateness of opioid therapy. Physicians need better education and training to address such difficult situations. PERSPECTIVE: The more frequent use of opioid therapy among patients who reported greater shared decision-making with their physicians underscores the need for better medical education and training in dealing with the complex issues and challenges pertaining to serial assessments of the appropriateness of opioid therapy for chronic pain.

Psychometric Properties and Domains Covered by Patient-Reported Outcome Measures Used in Trials Assessing Interventions for Chronic Pain.

OBJECTIVE: To identify the patient reported outcome measures (PROMs) used in clinical trials assessing interventions for chronic pain, describe their psychometric properties and the clinical domains they cover. STUDY DESIGN AND SETTING: We identified phase 3 or 4 interventional trials on adult participants (age >18) registered in clinicaltrials.gov between January 1, 2021 to December 31, 2022 and which provided "chronic pain" as a keyword condition. We excluded diagnostic studies and phase 1 or 2 trials. In each trial, one reviewer extracted all outcomes registered and identified those captured using PROMs. For each PROM used in more than 1% of identified trials, two reviewers assessed whether it covered the six important clinical domains from the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT): pain, emotional functioning, physical functioning, Participant ratings of global improvement of global improvement, symptoms and adverse events, and participant disposition (e.g., adherence to medication). Second, reviewers searched PubMed for both the initial publication and latest review reporting the psychometric properties of each PROM and their content validity, structural validity, internal consistency, reliability, measurement error, hypotheses testing, criterion validity and responsiveness using published criteria from the literature. RESULTS: In total, 596 trials assessing 4843 outcomes were included in the study (median sample size 60, interquartile range 40 to 100). Trials evaluated behavioral (22%), device-based (21%) and drug-based (10%) interventions. Of 495 unique PROMs, 55 were used in more than 1% trials (16 were generic pain measures; 8 were pain measures for specific diseases; 30 were measures of other symptoms or consequences of pain). About 50% PROMs had more than 50% of psychometric properties rated as sufficient. Scales often focused on a single clinical domain. Only 25% trials measured at least three clinical domains from IMMPACT. CONCLUSION: Only half of PROMs used in trials for chronic pain had sufficient psychometric properties for more than 50% of criteria assessed. Few PROMs assess more than one important clinical domain. Only 25% of trials measure more than 3/6 clinical domains considered important by IMMPACT.

Effects of Receiving Pain-Related Support on Psychological Well-Being: The Moderating Roles of Emotional Responses to Support.

OBJECTIVES: We investigated whether receiving greater pain-related instrumental support is associated with poorer psychological well-being among chronic pain patients who report less positive (e.g., grateful) or more negative (e.g., angry) emotional responses to support. METHODS: We conducted regression analyses, utilizing data from two waves of interviews with 152 knee osteoarthritis patients. Three indicators of psychological well-being were examined: depressive symptoms, positive affect, and negative affect. RESULTS: Receiving greater support was associated with poorer psychological well-being at baseline, as well as higher depressive symptoms and negative affect at the 18-month follow-up, only among patients with low positive emotional responses to support. Furthermore, receiving greater support was related to poorer psychological well-being at baseline only among patients with high negative emotional responses to support. DISCUSSION: Care recipients' less positive emotional responses to support may be a risk factor for poorer psychological well-being in both the short- and long-term, when receiving greater support.

Development of a Personalized Feedback Intervention Targeting Pain-Related Anxiety for Adults Reporting Hazardous Drinking and Chronic Pain: A Randomized Controlled Trial.

OBJECTIVE: Among individuals with chronic pain, the rate of hazardous alcohol use is elevated compared to the general population. Yet, hazardous drinkers with chronic pain remain an underserved group. There is a need to develop and test alternative and complementary interventions to reduce hazardous alcohol use among this high-risk segment of the general population; targeting pain-related anxiety, a candidate mechanism, is one theoretically-informed route. METHOD: Our approach followed a staged model (1a/1b) to develop and test a novel personalized feedback intervention (PFI). Phase 1A collected qualitative feedback from (N = 9; 77.8% female, Mage = 33.86, SD = 8.75) participants to refine intervention content and evaluate treatment acceptability and feasibility. For phase 1B, individuals (N=118; 57.3% male, Mage = 35.24, SD = 11.90) participated in a pilot randomized clinical trial for our novel PFI compared to a health information control condition on alcohol use, intention/motivation to reduce drinking, pain-related anxiety, and expectancies for alcohol analgesia/pain coping for hazardous drinkers with chronic pain. RESULTS: Phase 1a results provided support for the feasibility of using a PFI to target pain-related anxiety, and results from Phase 1b indicated that participants reduced drinking and primary outcomes changed in the expected directions, but there were no differential effects of the intervention. CONCLUSIONS: The current data provide preliminary evidence for the utility of computer-based brief interventions to encourage behavior change. However, further refinement of the intervention to target pain-related anxiety is warranted.

Healthcare experiences of fibromyalgia patients and their associations with satisfaction and pain relief. A patient survey.

OBJECTIVES: The etiology of fibromyalgia (FM) is disputed, and there is no established cure. Quantitative data on how this may affect patients' healthcare experiences are scarce. The present study aims to investigate FM patients' pain-related healthcare experiences and explore factors associated with high satisfaction and pain relief. METHODS: An anonymous, online, and patient-administered survey was developed and distributed to members of the Norwegian Fibromyalgia Association. It addressed their pain-related healthcare experiences from both primary and specialist care. Odds ratios for healthcare satisfaction and pain relief were estimated by binary logistic regression. Directed acyclic graphs guided the multivariable analyses. RESULTS: The patients (n = 1,626, mean age: 51 years) were primarily women (95%) with a 21.8-year mean pain duration and 12.7 years in pain before diagnosis. One-third did not understand why they had pain, and 56.6% did not know how to get better. More than half had not received satisfactory information on their pain cause from a physician, and guidance on how to improve was reported below medium. Patients regretted a lack of medical specialized competence on muscle pain and reported many unmet needs, including regular follow-up and pain assessment. Physician-mediated pain relief was low, and guideline adherence was deficient. Only 14.8% were satisfied with non-physician health providers evaluating and treating their pain, and 21.5% were satisfied (46.9% dissatisfied) with their global pain-related healthcare. Patients' knowledge of their condition, physicians' pain competence and provision of information and guidance, agreement in explanations and advice, and the absence of unmet needs significantly increased the odds of both healthcare satisfaction and pain relief. CONCLUSIONS: Our survey describes deficiencies in FM patients' pain-related healthcare and suggests areas for improvement to increase healthcare satisfaction and pain relief. (REC# 2019/845, 09.05.19).

Mindfulness-Based Therapy for Military Populations with Chronic Pain: A Systematic Review.

Background: Due to the limited role of chronic pain medication in military personnel and the distress caused to the military population, mindfulness-based therapy has been considered for the follow-up treatment of military personnel with chronic pain. The purpose of this review is to explore the effect and the implementation of mindfulness-based therapy for the military population with chronic pain. Methods: The keywords for the search included "mindfulness" AND ("pain" OR "chronic pain") AND ("military" OR "veteran"). The PubMed, Embase, and Cochrane Library databases were searched. The Cochrane Collaboration tool was used to independently assess the risk of bias of the included randomized controlled trials, and the Newcastle-Ottawa Scale was used to independently assess the risk of bias of the included case-control studies. Results: A total of 175 papers were identified; 65 duplicates were excluded, and 59 papers that did not meet the inclusion criteria were excluded after reading the titles and abstracts. The remaining 51 papers were read in full, 42 of which did not meet the inclusion criteria. Nine papers met the inclusion criteria and were included in the study. The nine studies included 507 veterans and 56 active-duty female military personnel. All pain interventions were mindfulness-based therapy, and all of them were integrated into or adapted from standard mindfulness courses. The results all showed that after mindfulness-based therapy, the relevant indicators improved. Conclusions: Mindfulness-based therapy is an effective treatment method for the military population with chronic pain. The review indicates that future research should focus on the best setting for mindfulness-based therapy, including the course content and time.

Identifying Predictors of Neck Disability in Patients with Cervical Pain Using Machine Learning Algorithms: A Cross-Sectional Correlational Study.

(1) Background: Neck pain intensity, psychosocial factors, and physical function have been identified as potential predictors of neck disability. Machine learning algorithms have shown promise in classifying patients based on their neck disability status. So, the current study was conducted to identify predictors of neck disability in patients with neck pain based on clinical findings using machine learning algorithms. (2) Methods: Ninety participants with chronic neck pain took part in the study. Demographic characteristics in addition to neck pain intensity, the neck disability index, cervical spine contour, and surface electromyographic characteristics of the axioscapular muscles were measured. Participants were categorised into high disability and low disability groups based on the median value (22.2) of their neck disability index scores. Several regression and classification machine learning models were trained and assessed using a 10-fold cross-validation method; also, MANCOVA was used to compare between the two groups. (3) Results: The multilayer perceptron (MLP) revealed the highest adjusted R2 of 0.768, while linear discriminate analysis showed the highest receiver characteristic operator (ROC) area under the curve of 0.91. Pain intensity was the most important feature in both models with the highest effect size of 0.568 with p < 0.001. (4) Conclusions: The study findings provide valuable insights into pain as the most important predictor of neck disability in patients with cervical pain. Tailoring interventions based on pain can improve patient outcomes and potentially prevent or reduce neck disability.

Impaired Carbohydrate Metabolism among Women with Chronic Low Back Pain and the Role of Dietary Carbohydrates: A Randomized Controlled Cross-Over Experiment.

Background: Impaired glucose regulation is suggested to be related to chronic low back pain (CLBP), although it is not clear how they interact with each other. Thus, the primary aim of this study was to investigate differences in postprandial glycemic responses (PPGRs) (the first sign of impaired glucose metabolism) to high- (sucrose) and low-glycemic index (GI) (isomaltulose) beverages in normoglycemic women with CLBP and healthy controls (HCs) and explore whether any group that showed greater PPGRs to high-GI beverage intake would benefit when the high-GI beverage was replaced with a low-GI beverage. Secondly, this study aimed to explore the association between PPGR and pain in patients with CLBP. Methods: This study was registered at clinicaltrials.org (NCT04459104) before the start of the study. In this study, 53 CLBP patients and 53 HCs were recruited. After 11-12 h of fasting, each participant randomly received isomaltulose or sucrose. Blood glucose levels were measured during the fasting state and 15, 30, 45, 60, 90, and 120 min after the beverage intake, and each participant underwent experimental pain measures. Results: Compared to the HCs, the CLBP group showed significantly higher PPGRs to sucrose (p < 0.021). Additionally, the CLBP group showed a significantly higher decrease in PPGR (p = 0.045) when comparing PPGR to sucrose with PPGR to isomaltulose. Correlation analysis revealed a positive association between self-reported pain sensitivity and PPGR to sucrose, while there was no association found between any experimental pain measures and glycemic responses. Conclusions: Overall, these findings suggest that normoglycemic CLBP patients might have a higher risk of developing impaired glucose tolerance than the HCs and might benefit more when high-GI foods are replaced with low-GI ones.

Prescription opioid dispensing patterns among patients with schizophrenia or bipolar disorder.

BACKGROUND: Patients with schizophrenia (SZ) or bipolar disorder (BD) may have increased risk of complications from prescribed opioids, including opioid-induced respiratory depression. We compared prescription opioid pain medication dispensing for patients with SZ or BD versus controls over 5 years to assess dispensing trends. METHODS: This retrospective, observational study analysed US claims data from the IBM® MarketScan® Commercial and Multi-State Medicaid databases for individuals aged 18-64 years with prevalent SZ or BD for years 2015-2019 compared with age- and sex-matched controls. Baseline characteristics, comorbidities, and medication use were assessed. Proportions of individuals dispensed prescription opioids chronically (ie, ≥70 days over a 90-day period or ≥ 6 prescriptions annually) or nonchronically (≥1 prescription, chronic definition not met) were assessed. RESULTS: In 2019, the Commercial and Medicaid databases contained records for 4773 and 30,179 patients with SZ and 52,780 and 63,455 patients with BD, respectively. Patients with SZ or BD had a higher prevalence of comorbidities, including pain, versus controls in each analysis year. From 2015 to 2019, among commercially insured patients with SZ, chronic opioid-dispensing proportions decreased from 6.1% (controls: 2.7%) to 2.3% (controls: 1.2%) and, for patients with BD, from 11.4% (controls: 2.7%) to 6.4% (controls: 1.6%). Chronic opioid dispensing declined in Medicaid-covered patients with SZ from 15.0% (controls: 14.7%) to 6.7% (controls: 6.0%) and, for patients with BD, from 27.4% (controls: 12.0%) to 12.4% (controls: 4.7%). Among commercially insured patients with SZ, nonchronic opioid dispensing decreased from 15.5% (controls: 16.4%) to 10.7% (controls: 11.0%) and, for patients with BD, from 26.1% (controls: 17.5%) to 20.0% (controls: 12.2%). In Medicaid-covered patients with SZ, nonchronic opioid dispensing declined from 22.5% (controls: 24.4%) to 15.1% (controls: 12.7%) and, for patients with BD, from 32.3% (controls: 25.9%) to 24.6% (controls: 13.6%). CONCLUSIONS: The proportions of individuals dispensed chronic or nonchronic opioid medications each year were similar between commercially and Medicaid-insured patients with SZ versus controls and were higher for patients with BD versus controls. From 2015 to 2019, the proportions of individuals who were dispensed prescription opioids chronically or nonchronically decreased for patients with SZ or BD and controls.

Peripheral direct current reduces naturally evoked nociceptive activity at the spinal cord in rodent models of pain.

Objective.Electrical neuromodulation is an established non-pharmacological treatment for chronic pain. However, existing devices using pulsatile stimulation typically inhibit pain pathways indirectly and are not suitable for all types of chronic pain. Direct current (DC) stimulation is a recently developed technology which affects small-diameter fibres more strongly than pulsatile stimulation. Since nociceptors are predominantly small-diameter Aδand C fibres, we investigated if this property could be applied to preferentially reduce nociceptive signalling.Approach.We applied a DC waveform to the sciatic nerve in rats of both sexes and recorded multi-unit spinal activity evoked at the hindpaw using various natural stimuli corresponding to different sensory modalities rather than broad-spectrum electrical stimulus. To determine if DC neuromodulation is effective across different types of chronic pain, tests were performed in models of neuropathic and inflammatory pain.Main results.We found that in both pain models tested, DC application reduced responses evoked by noxious stimuli, as well as tactile-evoked responses which we suggest may be involved in allodynia. Different spinal activity of different modalities were reduced in naïve animals compared to the pain models, indicating that physiological changes such as those mediated by disease states could play a larger role than previously thought in determining neuromodulation outcomes.Significance.Our findings support the continued development of DC neuromodulation as a method for reduction of nociceptive signalling, and suggests that it may be effective at treating a broader range of aberrant pain conditions than existing devices.