Sex-specific post-inflammatory dysbiosis mediates chronic visceral pain in colitis.

BACKGROUND: Despite achieving endoscopic remission, over 20% of inflammatory bowel disease (IBD) patients experience chronic abdominal pain. Visceral pain and the microbiome exhibit sex-dependent interactions, while visceral pain in IBD shows a sex bias. Our aim was to evaluate whether post-inflammatory microbial perturbations contribute to visceral hypersensitivity in a sex-dependent manner. METHODS: Males, cycling females, ovariectomized, and sham-operated females were given dextran sodium sulfate to induce colitis and allowed to recover. Germ-free recipients received sex-appropriate and cross-sex fecal microbial transplants (FMT) from post-inflammatory donor mice. Visceral sensitivity was assessed by recording visceromotor responses to colorectal distention. The composition of the microbiota was evaluated via 16S rRNA gene V4 amplicon sequencing, while the metabolome was assessed using targeted (short chain fatty acids - SCFA) and semi-targeted mass spectrometry. RESULTS: Post-inflammatory cycling females developed visceral hyperalgesia when compared to males. This effect was reversed by ovariectomy. Both post-inflammatory males and females exhibited increased SCFA-producing species, but only males had elevated fecal SCFA content. FMT from post-inflammatory females transferred visceral hyperalgesia to both males and females, while FMT from post-inflammatory males could only transfer visceral hyperalgesia to males. CONCLUSIONS: Female sex, hormonal status as well as the gut microbiota play a role in pain modulation. Our data highlight the importance of considering biological sex in the evaluation of visceral pain.

Associations between pain-related fear and lumbar movement variability during activities of daily living in patients with chronic low back pain and healthy controls.

Low back pain (LBP) is a global issue involving biological, psychological, and social factors. Pain-related fear has been shown to influence movement behavior, however, its association with some measures of movement behavior, such as spinal movement variability, remains inconclusive. To further investigate this, spinal kinematics during various activities of daily living (i.e., walking, running, lifting, and stair climbing) of 49 patients with chronic LBP and a group of 51 sex-, age-, and BMI-matched healthy controls were used to calculate lumbar spine movement variability which was quantified using different indices (i.e., coefficient of variation, coupling angle variability in vector coding, deviation phase of the continuous relative phase and an angle-angular velocity variability). General and task-specific pain-related fear was assessed using the Tampa Scale of Kinesiophobia and the Photograph Series of Daily Activities-Short Electronic Version, respectively. Linear regression analyses showed no significant association between movement variability and pain-related fear, however, the sample consisted of younger individuals with moderate disability and with low levels of pain and pain-related fear. In addition, the different variability indices were weakly correlated and varied greatly depending on the method used and the task performed. Therefore, comparisons between studies with different movement variability calculation methods or different activities should be treated with caution.

Cortical kappa opioid receptors integrate negative affect and sleep disturbance.

Sleep disruption and negative affect are attendant features of many psychiatric and neurological conditions that are often co-morbid including major depressive disorder, generalized anxiety disorder and chronic pain. Whether there is a causal relationship between negative affect and sleep disruption remains unclear. We therefore asked if mechanisms promoting negative affect can disrupt sleep and whether inhibition of pathological negative affect can normalize disrupted sleep. Signaling at the kappa opioid receptor (KOR) elicits dysphoria in humans and aversive conditioning in animals. We tested the possibility that (a) increased KOR signaling in the anterior cingulate cortex (ACC), a brain region associated with negative emotions, would be sufficient to promote both aversiveness and sleep disruption and (b) inhibition of KOR signaling would normalize pathological negative affect and sleep disruption induced by chronic pain. Chemogenetic Gi-mediated inhibition of KOR-expressing ACC neurons produced conditioned place aversion (CPA) as well as sleep fragmentation in naïve mice. CRISPR/Cas9 editing of ACC KOR normalized both the negative affect and sleep disruption elicited by pathological chronic pain while maintaining the physiologically critical sensory features of pain. These findings suggest therapeutic utility of KOR antagonists for treatment of disease conditions that are associated with both negative affect and sleep disturbances.

Association between movement speed and instability catch kinematics and the differences between individuals with and without chronic low back pain.

Studies reported the existence of instability catch (IC) during trunk flexion in patients with chronic low back pain (CLBP). However, different movement speeds can cause different neuromuscular demands resulting in altered kinematic patterns. In addition, kinematic characterization corresponding to clinical observation of IC is still limited. Therefore, this study aimed to determine (1) the association between movement speed and kinematic parameters representing IC during trunk flexion and (2) the differences in kinematic parameters between individuals with and without CLBP. Fifteen no low back pain (NoLBP) and 15 CLBP individuals were recruited. Inertial measurement units (IMU) were attached to T3, L1, and S2 spinous processes. Participants performed active trunk flexion while IMU data were simultaneously collected. Total trunk, lumbar, and pelvic mean angular velocity (T_MV, L_MV, and P_MV), as well as number of zero-crossings, peak-to-peak, and area of sudden deceleration and acceleration (Num, P2P, and Area), were derived. Pearson's correlation tests were used to determine the association between T_MV and L_MV, P_MV, Num, P2P, and Area. An ANCOVA was performed to determine the difference in kinematic parameters between groups using movement speed as a covariate. Significant associations (P < 0.05) were found between movement speed and other kinematic parameters, except for Area. Results showed that L_MV significantly differed from the P_MV (P = 0.002) in the CLBP group, while a significant between-group difference (P = 0.037) was found in the P_MV. Additionally, significant between-group differences (P < 0.05) in P2P and Area were observed. The associations between movement speed and kinematic parameters suggest that movement speed changes can alter kinematic patterns. Therefore, clinicians may challenge lumbopelvic neuromuscular control by modifying movement speed to elicit greater change in kinematic patterns. In addition, the NoLBP group used shared lumbar and pelvic contributions, while the CLBP group used less pelvic contribution. Finally, P2P and Area appeared to offer the greatest sensitivity to differentiate between the groups. Overall, these findings may enhance the understanding of the mechanism underlying IC in CLBP.

A distinct neuronal ensemble of prelimbic cortex mediates spontaneous pain in rats with peripheral inflammation.

The absence of a comprehensive understanding of the neural basis of spontaneous pain limits the development of therapeutic strategies targeting this primary complaint of patients with chronic pain. Here we report a distinct neuronal ensemble within the prelimbic cortex which processes signals related to spontaneous pain in rats with chronic inflammatory pain. This neuronal ensemble specifically encodes spontaneous pain-related behaviors, independently of other locomotive and evoked behaviors. Activation of this neuronal ensemble elicits marked spontaneous pain-like behaviors and enhances nociceptive responses, whereas prolonged silencing of its activities alleviates spontaneous pain and promotes overall recovery from inflammatory pain. Notably, afferents from the primary somatosensory cortex and infralimbic cortex bidirectionally modulate the activities of the spontaneous pain-responsive prelimbic cortex neuronal ensemble and pain behaviors. These findings reveal the cortical basis of spontaneous pain at the neuronal level, highlighting a distinct neuronal ensemble within the prelimbic cortex and its associated pain-regulatory brain networks.

Pain neuroscience education and motor imagery-based exercise protocol for patients with fibromyalgia: A randomized controlled trial.

BACKGROUND: This study is a randomized controlled, biopsychosocial study investigating the effectiveness of pain neuroscience education (PNE) and motor imagery-based exercise protocol (MIEP) on fibromyalgia pain. METHODS: Our study has four groups (MIEP n = 12, PNE n = 12, MIEP + PNE n = 14, Control n = 12) and all participants (n = 50) consist of patients diagnosed with fibromyalgia with chronic back pain. The primary outcome measure was pain intensity, and secondary outcome measures were beliefs, kinesiophobia, anxiety-depression, cognitive-mood, self-esteem, and body awareness. RESULTS: A statistically significant decrease in pain intensity was observed in all experimental groups, without any group being superior (Visual Analog Scale [VAS]: MIEP + PNE p = .003, 95% confidence interval [CI], -4.7078 to -0.9922; MIEP p = .003, 95% CI, -5.4806 to -1.0194; PNE p = .002, 95% CI, -3.6139 to -1.5461). There was a significant improvement in organic beliefs in both groups where PNE was applied (MIEP + PNE: p = .017, 95% CI, -7.8211 to -0.3189; PNE: p = .003, 95% CI, -9.7999 to -0.0401). A significant superiority in organic pain beliefs was detected in the MIEP + PNE group compared to the control group (p = .008, 95% CI, 1.7241-9.4959). CONCLUSIONS: According to this study, in which MIEP and PNE were combined, there was a decrease in pain intensity when both applications were applied together and when they were applied one by one. MIEP has improved her motor imagery ability, improved pain and increased body awareness. PNE has improved people's organic pain beliefs; removed people from fears, catastrophizing, and negative thoughts about pain; improved easier management of psychological processes and cognitive-emotion regulation ability.

The endocannabinoid system as a therapeutic target in neuropathic pain: a review.

INTRODUCTION: This review highlights the critical role of the endocannabinoid system (ECS) in regulating neuropathic pain and explores the therapeutic potential of cannabinoids. Understanding the mechanisms of the ECS, including its receptors, endogenous ligands, and enzymatic routes, can lead to innovative treatments for chronic pain, offering more effective therapies for neuropathic conditions. This review bridges the gap between preclinical studies and clinical applications by emphasizing ECS modulation for better pain management outcomes. AREAS COVERED: A review mapped the existing literature on neuropathic pain and the effects of modulating the ECS using natural and synthetic cannabinoids. This analysis examined ECS components and their alterations in neuropathic pain, highlighting the peripheral, spinal, and supraspinal mechanisms. This review aimed to provide a thorough understanding of the therapeutic potential of cannabinoids in the management of neuropathic pain. EXPERT OPINION: Advances in cannabinoid research have shown significant potential for the management of chronic neuropathic pain. The study emphasizes the need for high-quality clinical trials and collaborative efforts among researchers, clinicians, and regulatory bodies to ensure safe and effective integration of cannabinoids into pain management protocols. Understanding the mechanisms and optimizing cannabinoid formulations and delivery methods are crucial for enhancing therapeutic outcomes.

ADHD-pain: Characteristics of chronic pain and association with muscular dysregulation in adults with ADHD.

OBJECTIVES: A high incidence of attention-deficit hyperactivity disorder (ADHD) has been reported in chronic pain (ChP) patients. Furthermore, an association between ChP and muscular dysregulation has been reported in adults with ADHD. The present study investigated whether ADHD was more prevalent among psychiatric outpatients with ChP than those without ChP, and if there was an association between ChP, muscular dysregulation and characteristics of pain in patients with ADHD. METHODS: One-hundred and twenty-one individuals remitted to an outpatient psychiatry unit took part in this naturalistic epidemiological cross-sectional study. They were assessed with a pain self-report form (localization, intensity, and onset) and a test of muscle dysregulation (the Motor Function Neurological Assessment). Prevalence of ADHD among patients with ChP, as well as the qualitative characteristics of ChP within the ADHDgroup are reported. Both ChP and pain intensity correlated with muscular dysregulation through Spearman's rho analysis. Additionally, the relationship between various diagnostic categories (ADHD, affective disorders, anxiety, or personality disorders) and incidence of axial pain was evaluated in logistic regression. RESULTS: ADHD was significantly more prevalent in patients with ChP, than in patients without ChP. In the ADHD group, ChP and pain intensity was associated with muscular dysregulation, particularly with high muscle tone. ChP was more axial and widespread, than for the patients without ADHD, and started at an early age. ADHD diagnosis predicted axial pain, whereas affective-, anxiety-, or personality disorders did not. CONCLUSIONS: The study suggests that ChP in ADHD is associated with muscular dysregulation and is qualitatively different from ChP in psychiatric patients without ADHD. These findings may lead to further understanding of potential mechanisms involved in ADHD and ChP, and in turn to new treatment strategies for both disorders.

Identifying the Problem Side with Single-Leg Squat and Hamstrings Flexibility for Non-Specific Chronic Low Back Pain.

Background and Objectives: In patients with non-specific chronic low back pain (LBP), their pain and problem sides can differ. Clinical Pilates assessment provides an approach to identify the problem side, but this approach requires experience and can be subjective. This study aimed to investigate if objective measures of single-leg squat postural control and hamstrings flexibility could identify the problem side in adults with non-specific chronic LBP. Materials and Methods: Forty adults with non-specific chronic LBP were tested on single-leg squat postural control and hamstrings flexibility. The problem side of participants was assessed with the Clinical Pilates method. Paired t-tests were used to compare the postural sway parameters of the single-leg squat and hamstrings flexibility between the problem and non-problem sides. Cohen's kappa was then used to assess the agreement of postural sway and flexibility measures with the Clinical Pilates method. Results: The problem side showed smaller vertical force variance, larger sway path distances, lower peak vertical force, smaller terminal knee flexion angle, longer time to complete the five single-leg squats, and tighter hamstrings as compared to the non-problem side. However, only the overall and anteroposterior sway path distances, terminal knee flexion angle, total squat duration, and hamstrings flexibility yielded moderate to strong agreement with the Clinical Pilates method. Conclusions: Single-leg squat postural sway parameters and hamstrings flexibility can objectively identify the problem side in adults with non-specific chronic LBP.

Effects of Integrating Jaw Opening and Closing Movements with Active Neck Exercises in the Management of Chronic Non-Specific Neck Pain: A Randomized Controlled Trial.

Background and Objectives: It has been seen that jaw opening is associated with neck extension and jaw closing is associated with neck flexion. This natural association between the jaw and neck can be used as a novel approach to treat chronic non-specific neck pain, although the effects of this concept have never been previously evaluated as a treatment strategy. This article intends to study the effects of integrating jaw opening and closing movements along with active neck exercises versus active neck exercises alone in the management of chronic non-specific neck pain. Materials and Methods: A total of 80 patients, aged 20 to 50, with chronic non-specific neck pain were included in a double-blind randomized controlled trial, conducted at the Sindh Institute of Physical Medicine and Rehabilitation, Karachi, Pakistan from 2018 to 2022. The patients were divided into two groups: Group A patients were assigned jaw movements with active neck exercises, while Group B patients were assigned only active neck exercises. Both groups were assigned isometric strengthening exercises and self-resisted strengthening exercises for cervical spine muscles as a home plan. The study used various outcome measures, including the numerical pain rating scale (NPRS), neck disability index (NDI), neck flexion endurance (NFE), neck extension endurance (NEE), the neck proprioception error (NPE): neck flexion proprioception error (NFPE), neck extension proprioception error (NEPE), neck right rotation proprioception error (NRRPE), and neck left rotation proprioception error (NLRPE), with measurements taken at week 1 and week 6, respectively; the mean differences between the groups were measured using a two-way repeated ANOVA. Results: The experimental group showed better improvements compared to the control group, NPRS (73%), NDI (57%), NFE (152%), NEE (83%), NFPE (58%), NEPE (65%), NRRPE (65%), and NLRPE (62%), with a significant difference (p < 0.05). Conclusions: Active neck extension and flexion movements combined with jaw opening and closing are more effective in reducing pain and disability, improving neck muscles endurance and normalizing neck proprioception in patients with chronic neck pain.

Diurnal cortisol patterns in chronic pain: Associations with work-family spillover, work, and home stress.

Chronic pain is a prevalent condition with significant impacts on individuals' lives, including heightened stress and impaired physiological functioning. Given that work and family are the two main social domains where stress manifests, this study aimed to investigate the interactions between chronic pain, work-family stressors, and diurnal cortisol patterns to understand how chronic pain affects daily life and physiological stress responses. We identified 1,413 adults with chronic pain and 1,413 matched controls within MIDUS II samples to examine work-family spillover, daily work and home stressors, and cortisol levels across multiple days. The chronic pain group reported more negative work to family spillover and experienced more instances of stressful home events, particularly avoided arguments. These results align with literature suggesting chronic pain exacerbates tensions in close relationships and increases stress. The chronic pain group also had higher cortisol levels cross late-day periods, indicative of hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This dysregulation is associated with poorer health outcomes, including increased inflammation and psychological distress. We did not find any differences in previously identified cortisol profiles, which are higher-level summaries of cortisol levels within each day. We discuss why such difference might not have appeared in this sample.

Data-driven analysis of whole-brain intrinsic connectivity in patients with chronic low back pain undergoing osteopathic manipulative treatment.

BACKGROUND: Chronic Low Back Pain (cLBP) poses a significant health challenge, leading to functional disability and reduced quality of life. Osteopathic Manipulative Treatment (OMT) is emerging as a therapeutic option for cLBP, but the brain mechanisms underlying its analgesic effect remain unclear. MATERIALS AND METHODS: Thirty cLBP patients were randomly exposed to either four weekly sessions of OMT (N=16) or Sham treatment (N=14). Resting-state Magnetic Resonance Imaging (rs-MRI) scans and pain perception questionnaires were collected before and after treatment. A voxel-wise, rs-fMRI data-driven analysis was conducted to identify changes in the intrinsic functional connectivity across the whole brain that were associated with the OMT. Spearman's correlations were used to test for the association between changes in intrinsic connectivity and individual reports of pain perception. RESULTS: Compared to the Sham group, participants who received OMT showed significant alterations in the functional connectivity of several regions belonging to the pain matrix. Specifically, OMT was associated with decreased connectivity of a parietal cluster that includes the somatosensory cortex and an increase of connectivity of the right anterior insula and ventral and dorsal anterolateral prefrontal areas. Crucially, the change in connectivity strength observed in the ventral anterolateral prefrontal cortex, a putative region of the affective-reappraisive layer of the pain matrix, correlates with the reduction in pain perception caused by the OMT. CONCLUSIONS: This study offers insights into the brain mechanisms underlying the analgesic effect of OMT. Our findings support a link between OMT-driven functional cortical architecture alterations and improved clinical outcomes.

Neuropathic pain has sex-specific effects on oxycodone-seeking and non-drug-seeking ensemble neurons in the dorsomedial prefrontal cortex of mice.

Approximately 50 million Americans suffer from chronic pain, and nearly a quarter of chronic pain patients have reported misusing opioid prescriptions. Repeated drug seeking is associated with reactivation of an ensemble of neurons sparsely scattered throughout the dorsomedial prefrontal cortex (dmPFC). Prior research has demonstrated that chronic pain increases intrinsic excitability of dmPFC neurons, which may increase the likelihood of reactivation during drug seeking. We tested the hypothesis that chronic pain would increase oxycodone-seeking behaviour and that the pain state would differentially increase intrinsic excitability in dmPFC drug-seeking ensemble neurons. TetTag mice self-administered intravenous oxycodone. After 7 days of forced abstinence, a drug-seeking session was performed, and the ensemble was tagged. Mice received spared nerve injury (SNI) to induce chronic pain during the period between the first and second seeking session. Following the second seeking session, we performed electrophysiology on individual neurons within the dmPFC to assess intrinsic excitability of the drug-seeking ensemble and non-ensemble neurons. SNI had no impact on sucrose seeking or intrinsic excitability of dmPFC neurons from these mice. In females, SNI increased oxycodone seeking and intrinsic excitability of non-ensemble neurons. In males, SNI had no impact on oxycodone seeking or neuron excitability. Data from females are consistent with clinical reports that chronic pain can promote drug craving and relapse and support the hypothesis that chronic pain itself may lead to neuroadaptations which promote opioid seeking.

The brain's duck test in phantom percepts: Multisensory congruence in neuropathic pain and tinnitus.

Chronic neuropathic pain and chronic tinnitus have been likened to phantom percepts, in which a complete or partial sensory deafferentation results in a filling in of the missing information derived from memory. 150 participants, 50 with tinnitus, 50 with chronic pain and 50 healthy controls underwent a resting state EEG. Source localized current density is recorded from all the sensory cortices (olfactory, gustatory, somatosensory, auditory, vestibular, visual) as well as the parahippocampal area. Functional connectivity by means of lagged phase synchronization is also computed between these regions of interest. Pain and tinnitus are associated with gamma band activity, reflecting prediction errors, in all sensory cortices except the olfactory and gustatory cortex. Functional connectivity identifies theta frequency connectivity between each of the sensory cortices except the chemical senses to the parahippocampus, but not between the individual sensory cortices. When one sensory domain is deprived, the other senses may provide the parahippocampal 'contextual' area with the most likely sound or somatosensory sensation to fill in the gap, applying an abductive 'duck test' approach, i.e., based on stored multisensory congruence. This novel concept paves the way to develop novel treatments for pain and tinnitus, using multisensory (i.e. visual, vestibular, somatosensory, auditory) modulation with or without associated parahippocampal targeting.

Reduced variability of erector spinae activity in people with chronic low back pain when performing a functional 3D lifting task.

BACKGROUND: Chronic low back pain (LBP) is a leading cause of disability, which is exacerbated in some by repeated lifting. Electromyography (EMG) assessments of isolated erector spinae (ES) regions during lifting identified conflicting results. Here, high-density EMG comprehensively assesses the lumbar and thoracolumbar ES activity in people with and without LBP performing a multiplanar lifting task. METHODS: Four high-density EMG grids (two bilaterally) and reflective markers were affixed over the ES and trunk to record muscle activity and trunk kinematics respectively. The task involved cyclical lifting of a 5 kg box for ∼7 min from a central shelf to five peripheral shelves, returning to the first between movements, while monitoring perceived exertion. RESULTS: Fourteen LBP (26.9 ± 11.1 years) and 15 control participants (32.1 ± 14.6 years) completed the study. LBP participants used a strategy characterised by less diffuse and more cranially-focussed ES activity (P < 0.05). LBP participants also exhibited less variation in ES activity distribution between sides during movements distal to the central shelf (P < 0.05). There were few consistent differences in kinematics, but LBP participants reported greater exertion (P < 0.05). CONCLUSION: In the presence of mild LBP, participants used a less variable motor strategy, with less diffuse and more cranially-focussed ES activity; this motor strategy occurred concomitantly with increased exertion while completing this dynamic task.

Pain-related threat and coordination in adults with chronic low back pain during a lifting task: A cross-sectional study.

OBJECTIVES: People with low back pain (LBP) exhibit altered coordination, possibly indicating guarded movement. The connection between these changes and pain-related threat remains unclear. We aimed to determine if pain-related threat was related to spinal coordination and variability, during a lifting task, in people with chronic LBP. METHODS: Participants were adults with chronic LBP (n = 47). Upper lumbar, lower lumbar, and hipkinematics were measured during 10crate lifting/lowering repetitions. Coordination and variability of the Hip-Lower Lumbar, and Lower Lumbar-Upper Lumbar joint pairs were calculated. Pain-related threat was measured using the Tampa Scale for Kinesiophobia, the Pain Catastrophizing Scale, and task-specific fear. Linear regression analyses tested the relationship between pain-related threat and coordination. RESULTS: Adding catastrophizing to our base model (sex) explained variance in Hip-Lower lumbar coordination (r2 change = 0.125, p = 0.013). General and task specific measures of fear were unrelated to coordination and variability at both joint pairs (r2 change < 0.064, p > 0.05). Exploratory t-tests revealed subgroups aligned with phenotypes of "tight" and "loose" control, where "tight" control was characterized by greater catastrophizing and disability. CONCLUSION: Pain catastrophizing, but not measures of fear, was related to more in-phase ("tight") Hip-Lower Lumbar coordination during lifting/lowering. Considering this relationship based on subgroups may add clarity.

Algorithm Validation for Quantifying ActiGraph™ Physical Activity Metrics in Individuals with Chronic Low Back Pain and Healthy Controls.

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™.

Resting-state frontal electroencephalography (EEG) biomarkers for detecting the severity of chronic neuropathic pain.

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.

Precision of trunk movement in people with chronic low back pain.

BACKGROUND: Motor control exercise is commonly applied in people with chronic low back pain (CLBP), but possibly not all people with CLBP have motor control impairments. We suggest movement precision as measure to identify motor control impairments. Movement precision has been operationalized as trunk movement variability (TMV) and as trunk tracking error(s) (TTE). OBJECTIVES: To compare the known-group validity and the responsiveness of TMV and TTE. DESIGN: We used a case-control comparison (Healthy controls (n = 30) vs CLBP (n = 60)) to assess the known-group validity. A cohort study, (measurements in week 3 and week 12 of treatment), was used to assess responsiveness. METHODS: TMV (temporal (CyclSD) and spatial (MeanSD)) was analyzed during standing, repetitive flexion and rotation tasks (35x). TTE was measured during movement target tracking tasks, again in flexion and rotation. Participants with CLBP followed a multidisciplinary intervention and both measures were assessed in week 3 and week 12 of treatment. 2-way MANOVA and 2-way ANOVA were used to assess the effect of Group (CLBP vs healthy controls) and direction (flexion vs rotation) on TMV and TTE. For responsiveness, 2-way MANOVA and 2-way ANOVA were used to assess the effect of treatment and direction on both measures. FINDINGS: At baseline, TMV was not different between groups, while TTE was higher in the people with CLBP (p = 0.005, np2 = 0.09). Treatment strongly decreased temporal TMV (p = 0.025, np2 = 0.33) and TTE (p < 0.001, np2 = 0.844). CONCLUSIONS: These results demonstrate that TTE is more sensitive to CLBP and more responsive to treatment than TMV.

The Locus Coeruleus in Chronic Pain.

Pain perception is the consequence of a complex interplay between activation and inhibition. Noradrenergic pain modulation inhibits nociceptive transmission and pain perception. The main source of norepinephrine (NE) in the central nervous system is the Locus Coeruleus (LC), a small but complex cluster of cells in the pons. The aim of this study is to review the literature on the LC-NE inhibitory system, its influence on chronic pain pathways and its frequent comorbidities. The literature research showed that pain perception is the consequence of nociceptive and environmental processing and is modulated by the LC-NE system. If perpetuated in time, nociceptive inputs can generate neuroplastic changes in the central nervous system that reduce the inhibitory effects of the LC-NE complex and facilitate the development of chronic pain and frequent comorbidities, such as anxiety, depression or sleeping disturbances. The exact mechanisms involved in the LC functional shift remain unknown, but there is some evidence that they occur through plastic changes in the medial and lateral pathways and their brain projections. Additionally, there are other influencing factors, like developmental issues, neuroinflammatory glial changes, NE receptor affinity and changes in LC neuronal firing rates.