Resting-state brain activity as a biomarker of chronic pain impairment and a mediator of its association with pain resilience.

Past cross-sectional chronic pain studies have revealed aberrant resting-state brain activity in regions involved in pain processing and affect regulation. However, there is a paucity of longitudinal research examining links of resting-state activity and pain resilience with changes in chronic pain outcomes over time. In this prospective study, we assessed the status of baseline (T1) resting-state brain activity as a biomarker of later impairment from chronic pain and a mediator of the relation between pain resilience and impairment at follow-up. One hundred forty-two adults with chronic musculoskeletal pain completed a T1 assessment comprising a resting-state functional magnetic resonance imaging scan based on regional homogeneity (ReHo) and self-report measures of demographics, pain characteristics, psychological status, pain resilience, pain severity, and pain impairment. Subsequently, pain impairment was reassessed at a 6-month follow-up (T2). Hierarchical multiple regression and mediation analyses assessed relations of T1 ReHo and pain resilience scores with changes in pain impairment. Higher T1 ReHo values in the right caudate nucleus were associated with increased pain impairment at T2, after controlling for all other statistically significant self-report measures. ReHo also partially mediated associations of T1 pain resilience dimensions with T2 pain impairment. T1 right caudate nucleus ReHo emerged as a possible biomarker of later impairment from chronic musculoskeletal pain and a neural mechanism that may help to explain why pain resilience is related to lower levels of later chronic pain impairment. Findings provide empirical foundations for prospective extensions that assess the status of ReHo activity and self-reported pain resilience as markers for later impairment from chronic pain and targets for interventions to reduce impairment. PRACTITIONER POINTS: Resting-state markers of impairment: Higher baseline (T1) regional homogeneity (ReHo) values, localized in the right caudate nucleus, were associated with exacerbations in impairment from chronic musculoskeletal pain at a 6-month follow-up, independent of T1 demographics, pain experiences, and psychological factors. Mediating role of ReHo values: ReHo values in the right caudate nucleus also mediated the relationship between baseline pain resilience levels and later pain impairment among participants. Therapeutic implications: Findings provide empirical foundations for research extensions that evaluate (1) the use of resting-state activity in assessment to identify people at risk for later impairment from pain and (2) changes in resting-state activity as biomarkers for the efficacy of treatments designed to improve resilience and reduce impairment among those in need.

Vertebral bone quality score was associated with paraspinal muscles fat infiltration, but not modic classification in patients with chronic low back pain: a prospective cross-sectional study.

BACKGROUND: The lumbar vertebra and paraspinal muscles play an important role in maintaining the stability of the lumbar spine. Therefore, the aim of this study was to investigate the relationship between paraspinal muscles fat infiltration and vertebral body related changes [vertebral bone quality (VBQ) score and Modic changes (MCs)] in patients with chronic low back pain (CLBP). METHODS: Patients with CLBP were prospectively collected in four hospitals and all patients underwent 3.0T magnetic resonance scanning. Basic clinical information was collected, including age, sex, course of disease (COD), and body mass index (BMI). MCs were divided into 3 types based on their signal intensity on T1 and T2-weighted imaging. VBQ was obtained by midsagittal T1-weighted imaging (T1WI) and calculated using the formula: SIL1-4/SICSF. The Proton density fat fraction (PDFF) values and cross-sectional area (CSA) of paraspinal muscles were measured on the fat fraction map from the iterative decomposition of water and fat with the echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) sequences and in/out phase images at the central level of the L4/5 and L5/S1 discs. RESULTS: This study included 476 patients with CLBP, including 189 males and 287 females. 69% had no Modic changes and 31% had Modic changes. There was no difference in CSA and PDFF for multifidus(MF) and erector spinae (ES) at both levels between Modic type I and type II, all P values>0.05. Spearman correlation analysis showed that VBQ was weakly negatively correlated with paraspinal muscles CSA (all r values < 0.3 and all p values < 0.05), moderately positive correlation with PDFF of MF at L4/5 level (r values = 0.304, p values<0.001) and weakly positively correlated with PDFF of other muscles (all r values<0.3 and all p values<0.001). Multivariate linear regression analysis showed that age (ß = 0.141, p < 0.001), gender (ß = 4.285, p < 0.001) and VBQ (ß = 1.310, p = 0.001) were related to the total PDFF of muscles. For MCs, binary logistic regression showed that the odds ratio values of age, BMI and COD were 1.092, 1.082 and 1.004, respectively (all p values ＜ 0.05). CONCLUSIONS: PDFF of paraspinal muscles was not associated with Modic classification. In addition to age and gender, PDFF of paraspinal muscles is also affected by VBQ. Age and BMI are considered risk factors for the MCs in CLBP patients.

Prevalence and location of inflammatory and structural lesions in patients with rheumatoid arthritis and radiographic axial spondyloarthritis with chronic neck pain evaluated by magnetic resonance imaging.

OBJECTIVE: Define the prevalence and location of inflammatory and structural lesions on magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) and radiographic axial spondyloarthritis (r-axSpA) with neck pain as leading clinical symptom. METHODS: Patients with diagnosis of RA and r-axSpA were consecutively included if they had chronic (> 3 months) neck pain. Clinical assessment, neck pain questionnaires and MRIs of the cervical spine (CS) were performed. RESULTS: 107 patients (59 RA and 48 r-axSpA) were included. While there was no difference in the Northwick-Park-Neck-Pain-questionnaire, patients with RA reported higher neck pain compared to r-axSpA on a numeric rating scale (5.0 ± 3.6 vs. 3.0 ± 3.1; p = 0.003). Inflammatory lesions occurred predominantly in the craniocervical area in RA and in the lower CS segments in r-axSpA. Bone marrow edema (BME) was more frequent in axSpA (BME-score axSpA/RA: 0.35vs0.17; p < 0.001) while synovitis was visible in both but was more prevalent in RA (synovitis-score axSpA/RA: 0.02vs0.1; p < 0.001). BME was found in 8 (13.6%) vertebral corner vs. 9 (18.8%), in 2 (3.4%) facet joints vs. 7 (14.6%) and in 1 (1.7%) spinous processes vs. 9 (18.8%) in patients with RA/r-axSpA. In contrast, more patients with RA (30.5% vs6.3%) showed erosive osteochondrosis with endplate BME (p = 0.002). CONCLUSION: While involvement of upper cervical inflammation was typically present in RA, r-axSpA patients showed more BME in lower CS segments, vertebral corners, facet joints and spinous processes. Neck pain is linked to upper and lower inflammatory and structural lesions of the CS in both diseases.

Bibliometric analysis of functional magnetic resonance imaging studies on chronic pain over the past 20 years.

PURPOSE: The utilization of functional magnetic resonance imaging (fMRI) in studying the mechanisms and treatment of chronic pain has gained significant popularity. However, there is currently a dearth of literature conducting bibliometric analysis on fMRI studies focused on chronic pain. METHODS: All the literature included in this study was obtained from the Science Citation Index Expanded of Web of Science Core Collection. We used CiteSpace and VOSviewer to analyze publications, authors, countries or regions, institutions, journals, references and keywords. Additionally, we evaluated the timeline and burst analysis of keywords, as well as the timeline and burst analysis of references. The search was conducted from 2004 to 2023 and completed within a single day on October 4th, 2023. RESULTS: A total of 1,327 articles were retrieved. The annual publication shows an overall increasing trend. The United States has the highest number of publications and the main contributing institution is Harvard University. The journal PAIN produces the most articles. In recent years, resting-state fMRI, the prefrontal cortex, nucleus accumbens, thalamus, and migraines have been researched hotspots of fMRI studies on chronic pain. CONCLUSIONS: This study provides an in-depth perspective on fMRI for chronic pain research, revealing key points, research hotspots and research trends, which offers valuable ideas for future research activities. It concludes with a summary of advances in clinical practice in this area, pointing out the need for critical evaluation of these findings in the light of guidelines and expert recommendations. It is anticipated that further high-quality research outputs will be generated in the future, which will facilitate the utilization of fMRI in clinical decision-making for chronic pain.

Association of MRI findings with paraspinal muscles fat infiltration at lower lumbar levels in patients with chronic low back pain: a multicenter prospective study.

OBJECTIVE: In chronic low back pain (CLBP), the relationship between spinal pathologies and paraspinal muscles fat infiltration remains unclear. This study aims to evaluate the relationship between MRI findings and paraspinal muscles morphology and fat infiltration in CLBP patients by quantitative MRI. METHODS: All the CLBP patients were enrolled from July 2021 to December 2022 in four medical institutions. The cross-sectional area (CSA) and proton density fat fraction (PDFF) of the multifidus (MF) and erector spinae (ES) muscles at the central level of the L4/5 and L5/S1 intervertebral discs were measured. MRI findings included degenerative lumbar spondylolisthesis (DLS), intervertebral disc degeneration (IVDD), facet arthrosis, disc bulge or herniation, and disease duration. The relationship between MRI findings and the paraspinal muscles PDFF and CSA in CLBP patients was analyzed. RESULTS: A total of 493 CLBP patients were included in the study (198 females, 295 males), with an average age of 45.68 ± 12.91 years. Our research indicates that the number of MRI findings are correlated with the paraspinal muscles PDFF at the L4/5 level, but is not significant. Moreover, the grading of IVDD is the primary factor influencing the paraspinal muscles PDFF at the L4-S1 level (BES at L4/5=1.845, P < 0.05); DLS was a significant factor affecting the PDFF of MF at the L4/5 level (B = 4.774, P < 0.05). After including age, gender, and Body Mass Index (BMI) as control variables in the multivariable regression analysis, age has a significant positive impact on the paraspinal muscles PDFF at the L4-S1 level, with the largest AUC for ES PDFF at the L4/5 level (AUC = 0.646, cut-off value = 47.5), while males have lower PDFF compared to females. BMI has a positive impact on the ES PDFF only at the L4/5 level (AUC = 0.559, cut-off value = 24.535). CONCLUSION: The degree of paraspinal muscles fat infiltration in CLBP patients is related to the cumulative or synergistic effects of multiple factors, especially at the L4/L5 level. Although age and BMI are important factors affecting the degree of paraspinal muscles PDFF in CLBP patients, their diagnostic efficacy is moderate.

ACR Appropriateness Criteria® Chronic Hand and Wrist Pain: 2023 Update.

Chronic hand and wrist pain is a common presenting complaint. The intricate anatomy results in a variety of pain generators-multiple bones, articular cartilage, intrinsic ligaments, triangular fibrocartilage complex, joint capsules and synovium, tendons and tendon sheaths, muscles, and nerves-in a compact space. The need for imaging and the choice of the appropriate imaging modality are best determined by the patient's presentation, physical examination, and the clinician's working differential diagnosis. Radiography is usually appropriate as the initial imaging study in the evaluation of chronic hand or wrist pain. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Increased water content in multifidus muscles of young adults with chronic nonspecific low back pain detected by dual-energy CT and MRI.

OBJECTIVES: To demonstrate the feasibility of better diagnosing young adults with chronic nonspecific low back pain (CNLBP) by measuring water content in paraspinal muscles using water-muscle decomposition technique in dual-energy CT (DECT) and T2-mapping in MRI. METHODS: This prospective cross-sectional study included 110 young individuals (56 with CNLBP at age of 25.7 ± 2.0 years and 54 of asymptomatic at age of 25.1 ± 1.9 years) who underwent both MRI and DECT on the spine. T2 values on T2 mapping in MRI and water density (WD) value on water(muscle) images in DECT were generated at the L1-L4 levels for erector spinae muscle and L2-L5 for multifidus muscle. Pain duration time, Oswestry Disability Index (ODI), Visual Analogue Scale (VAS) were recorded for CNLBP patients. Difference of T2 value and WD between the two patient groups, and correlations between T2 value and WD, and T2 value and WD with clinical indicators were analyzed. RESULTS: Compared with asymptomatic participants, the mean WD of multifidus muscle at L4-L5 and mean T2 values of multifidus muscle at L5 were significantly higher in CNLBP patients (all P < 0.05). T2 values had moderate to strong positive correlations (r = 0.34-0.60, all P < 0.05) with DECT WD in CNLBP patients and healthy volunteers. There was a weak correlation between VAS and WD in L5-level multifidus muscle (r = 0.29, P < 0.05). CONCLUSIONS: The T2 values in MRI and WD in DECT are higher in multifidus muscles of lower vertebra levels for young CNLBP patients, and there exists positive correlation between WD and T2 values, providing useful information for diagnosing CNLBP.

Neuroimaging of opioid effects in humans across conditions of acute administration, chronic pain therapy, and opioid use disorder.

Evidence of central nervous system (CNS) exogenous opioid effects in humans has been primarily gained through neuroimaging of three participant populations: individuals after acute opioid administration, those with opioid use disorder (OUD), and those with chronic pain receiving opioid therapy. In both the brain and spinal cord, opioids alter processes of pain, cognition, and reward. Opioid-related CNS effects may persist and accumulate with longer opioid use duration. Meanwhile, opioid-induced benefits versus risks to brain health remain unclear. This review article highlights recent accumulating evidence for how exogenous opioids impact the CNS in humans. While investigation of CNS opioid effects has remained largely disparate across contexts of opioid acute administration, OUD, and chronic pain opioid therapy, integration across these contexts may enable advancement toward effective interventions.

The relationship between the psoas major muscle morphology characteristics with disability index and pain in patients with chronic nonspecific low back pain.

BACKGROUND: Chronic nonspecific low back pain (CNLBP) is a common disorder in people of active ages and significantly affects their quality of life. Different structures in the lumbar area can cause LBP. The lumbar muscle disorders, including the psoas major (PM) muscles, have an essential role in LBP. Magnetic Resonance Imaging (MRI) has been introduced as a safe and useful instrument for investigating the morphological properties of skeletal muscle. In general, PM morphology changes may be one reason for the pain and disability experienced in CNLBP patients. Thus, this study aimed to assess the relationship among the PM's Cross-sectional area (CSA), medial-lateral (ML), and anterior-posterior (AP) diameters, with disability index and pain score in patients with CNLBP. METHOD: One hundred twenty patients with CNLBP (60 men and 60 women) participated in this cross-sectional study. Axial MRIs were obtained from L3/L4 and L4/L5 disc levels. Then, patients filled out Rolland Morris Disability Questionnaires, demographic data forms, and the Numeric Pain Rating Scale (NPRS). Image J software was used to analyze the images. Using Linear Regression and the Pearson test, the correlation between muscle CSA and diameters, as well as data obtained from questionnaires and NPRS, was analyzed. RESULTS: Results from the statistical analysis showed no statistically significant relationship among morphological characteristics of the psoas major muscle in L3/L4 and L4/L5 disc levels with disability index and pain score (p < 0.05). CONCLUSIONS: There is no significant relationship between the PM morphological characteristics and disability index and pain score. Therefore, muscle CSA and diameters are insufficient to determine the cause of CNLBP.

Measuring myofascial shear strain in chronic shoulder pain with ultrasound shear strain imaging: a case report.

BACKGROUND: Dysfunctional gliding of deep fascia and muscle layers forms the basis of myofascial pain and dysfunction, which can cause chronic shoulder pain. Ultrasound shear strain imaging may offer a non-invasive tool to quantitatively evaluate the extent of muscular dysfunctional gliding and its correlation with pain. This case study is the first to use ultrasound shear strain imaging to report the shear strain between the pectoralis major and minor muscles in shoulders with and without chronic pain. CASE PRESENTATION: The shear strain between the pectoralis major and minor muscles during shoulder rotation in a volunteer with chronic shoulder pain was measured with ultrasound shear strain imaging. The results show that the mean ± standard deviation shear strain was 0.40 ± 0.09 on the affected side, compared to 1.09 ± 0.18 on the unaffected side (p<0.05). The results suggest that myofascial dysfunction may cause the muscles to adhere together thereby reducing shear strain on the affected side. CONCLUSION: Our findings elucidate a potential pathophysiology of myofascial dysfunction in chronic shoulder pain and reveal the potential utility of ultrasound imaging to provide a useful biomarker for shear strain evaluation between the pectoralis major and minor muscles.

Ultrasonographic measurement indicated patients with chronic neck pain had reduced diaphragm thickness and mobility along with declined respiratory functions.

BACKGROUND: Chronic neck pain (CNP) is a prevalent musculoskeletal condition including notable impairments in respiratory function. The diaphragm, serving dual roles in respiration and spinal stability, is intricately linked to the cervical spine through fascial, neurophysiological, and biomechanical connections. However, to date, none has investigated the diaphragm function in patients with CNP. OBJECTIVES: To investigate the diaphragm function, respiratory muscle strength, and pulmonary function in patients with CNP. In addition, their associations were also examined. DESIGN: A case-control study. METHODS: A total of 54 participants were recruited including 25 patients with CNP (CNP group) and 29 healthy adults (CON group). Pulmonary function including forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), and respiratory muscle strength represented by maximal inspiratory (MIP) and maximal expiratory pressure (MEP), as well as diaphragm function including ultrasonographic measures of mobility and thickness changes during maximal inspiration and expiration were assessed in all participants. Additionally, the intensity of pain and disability were evaluated using a Visual Analog Scale and Neck Disability Index only in patients with CNP. RESULTS: Significant reductions of the FVC, FEV1, MIP, and MEP were found in the CNP group compared to the CON group (p < 0.05). The diaphragm mobility and thickness changes were also significantly decreased in the CNP group than the CON group with medium effect sizes (p < 0.05). Only diaphragm thickness change was positively correlated with FVC, FEV1, and MEP in patients with CNP. Furthermore, MEP showed the strongest contribution to diaphragm thickness change based on the regression analysis. CONCLUSIONS: Impaired diaphragm function, respiratory muscle strength, and pulmonary function were observed in patients with CNP. Patients with smaller diaphragm thickness change had poorer pulmonary function and reduced maximal expiratory muscle strength. Diaphragm assessment and intervention may be considered in CNP management.

Thoracolumbar fascia and chronic low back pain in idiopathic lumbar scoliosis: an ultrasonographic study.

PURPOSE: The role of thoracolumbar fascia (TLF) in the development of chronic low back pain (CLBP) has growing evidence in the literature. Although CLBP is reported in individuals with idiopathic scoliosis (IS), its relationship with the TLF has yet not been established. This study aims to evaluate the TLF and its relationship with CLBP in IS. METHODS: A total of 60 individuals were included in the study. They were divided into three groups as follows: painful scoliosis (n = 20, age: 17.1 ± 3.7 years, Cobb angle: 15-43°), non-painful scoliosis (n = 20, age: 16.4 ± 3.4 years, Cobb angle: 15-45°), and healthy group (n = 20, age: 16.4 ± 4.7 years). Pain was evaluated using the short form of the McGill Pain Questionnaire. TLF thickness was evaluated on the lumbar region using ultrasonography. Trunk range of motion was assessed using a universal goniometer, and flexibility was assessed with sit-and-reach test. RESULTS: The thickness of the right TLF was greatest in the painful group, followed by non-painful (p = 0.007) and healthy (p < 0.001) groups. The thickness of the left TLF in the non-painful and painful groups was greater compared to the healthy group (p < 0.001). In the painful group, right TLF thickness was negatively correlated with trunk flexion/extension (r = -0.540, p = 0.014/r = -0.514, p = 0.020) and left rotation (r = -0.499, p = 0.025) but positively correlated with pain (r = 0.562, p = 0.01). CONCLUSIONS: Thickening of the TLF was observed in IS, whereby, in the presence of CLBP, it was further intensified. We suggest considering fascial thickening as a potential contributing factor to both pain and limited motion in relevant patients.

Insular cortex involvement in migraine patients with chronic pain: A volumetric radiological and clinical study.

BACKGROUND: This study aimed to assess abnormalities in the insular cortex of individuals suffering from migraines and examine their associations with pain duration, medication usage, and clinical symptoms. METHODS: We analyzed radiological data from 38 migraine patients who had undergone 3D iso T1-weighted brain MRI at our university hospital between 2019 and 2023. Structured questionnaires were used to collect information on participants' age, migraine type, disease duration, clinical symptoms, and medication use. Volumetric analysis was performed on the insular regions using Volbrain and 3DSlicer. The results were statistically analyzed. RESULTS: Comparing groups with chronic pain to normal groups revealed significant differences in several insular regions, including the posterior insula (p = 0.034), parietal operculum (p = 0.04), and the entire insular cortex (p = 0.023). Further group comparisons (Group 1, 2, and 3) showed significant differences in specific insular regions. For instance, the anterior insula (p = 0.032) was associated with taste changes, the posterior insula (p = 0.010) with smell-related changes, and the central operculum (p = 0.046) with sensations of nausea. Additionally, significant changes were observed in the parietal operculum concerning nausea, photophobia, phonophobia, and changes in smell. CONCLUSION: To the best of our knowledge, there have been no studies investigating the relationship between clinical manifestations and volumetric correlation. This study provides insights into abnormalities in the insular cortex among migraine patients and their potential relevance to pain duration, severity, and migraine type. The results suggest that understanding alterations in insular regions possibly linked to pain could contribute to the development of innovative approaches to managing chronic pain.

Altered cortical thickness and structural covariance networks in chronic low back pain.

BACKGROUND: Despite regional brain structural changes having been reported in patients with chronic low back pain (CLBP), the topological properties of structural covariance networks (SCNs), which refer to the organization of the SCNs, remain unclear. This study applied graph theoretical analysis to explore the alterations of the topological properties of SCNs, aiming to comprehend the integration and separation of SCNs in patients with CLBP. METHODS: A total of 38 patients with CLBP and 38 healthy controls (HCs), balanced for age and sex, were scanned using three-dimensional T1-weighted magnetic resonance imaging. The cortical thickness was extracted from 68 brain regions, according to the Desikan-Killiany atlas, and used to reconstruct the SCNs. Subsequently, graph theoretical analysis was employed to evaluate the alterations of the topological properties in the SCNs of patients with CLBP. RESULTS: In comparison to HCs, patients with CLBP had less cortical thickness in the left superior frontal cortex. Additionally, the cortical thickness of the left superior frontal cortex was negatively correlated with the Visual Analogue Scale scores of patients with CLBP. Furthermore, patients with CLBP, relative to HCs, exhibited lower global efficiency and small-worldness, as well as a longer characteristic path length. This indicates a decline in the brain's capacity to transmit and process information, potentially impacting the processing of pain signals in patients with CLBP and contributing to the development of CLBP. In contrast, there were no significant differences in the clustering coefficient, local efficiency, nodal efficiency, nodal betweenness centrality, or nodal degree between the two groups. CONCLUSIONS: From the regional cortical thickness to the complex brain network level, our study demonstrated changes in the cortical thickness and topological properties of the SCNs in patients with CLBP, thus aiding in a better understanding of the pathophysiological mechanisms of CLBP.

The effects of virtual reality neuroscience-based therapy on clinical and neuroimaging outcomes in patients with chronic back pain: a randomized clinical trial.

ABSTRACT: Chronic pain remains poorly managed. The integration of immersive technologies (ie, virtual reality [VR]) with neuroscience-based principles may provide effective pain treatment by targeting cognitive and affective neural processes that maintain pain and therefore potentially changing neurobiological circuits associated with pain chronification and amplification. We tested the effectiveness of a novel VR neuroscience-based therapy (VRNT) to improve pain-related outcomes in n = 31 participants with chronic back pain, evaluated against usual care (waitlist control; n = 30) in a 2-arm randomized clinical trial ( NCT04468074) . We also conducted pre-treatment and post-treatment MRI to test whether VRNT affects brain networks previously linked to chronic pain and treatment effects. Compared with the control condition, VRNT led to significantly reduced pain intensity (g = 0.63) and pain interference (g = 0.84) at post-treatment vs pre-treatment, with effects persisting at 2-week follow-up. These improvements were partially mediated by reduced kinesiophobia and pain catastrophizing. Several secondary clinical outcomes were also improved by VRNT, including disability, quality of life, sleep, and fatigue. In addition, VRNT was associated with increases in dorsomedial prefrontal functional connectivity with the superior somatomotor, anterior prefrontal and visual cortices, and decreased white matter fractional anisotropy in the corpus callosum adjacent to the anterior cingulate, relative to the control condition. Thus, VRNT showed preliminary efficacy in significantly reducing pain and improving overall functioning, possibly through changes in somatosensory and prefrontal brain networks.

Alterations in functional connectivity in patients with non-specific chronic low back pain after motor control exercise: a randomized trial.

BACKGROUND: Motor control exercise (MCE) is effective in alleviating non-specific chronic low back pain (NCLBP). Neuro-imaging research is warranted to explore the underlying neural mechanisms of MCE. AIM: We used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the central mechanism underpinning the effects of MCE in patients with NCLBP. DESIGN: A randomized, single-blinded, controlled trial. SETTING: The setting was out-patient and community. POPULATION: Fifty-eight patients with NCLBP. METHODS: Patients were randomized into the MCE or manual therapy (MT) group. All the participants completed pain-related clinical assessments and rs-fMRI scans before and after intervention. We performed exploratory whole-brain analyses in regional homogeneity (ReHo) and resting-state functional connectivity (rsFC) with significant post-pre differences in ReHo before and after intervention, and investigated associations between imaging and pain-related clinical assessments. RESULTS: Compared with the MT group, a greater alleviation in pain intensity and disability was observed in the MCE group after intervention, and was sustained at the 6-month follow-up (P<0.001). Only the MCE group showed increased ReHo values in the right pre-central gyrus and decreased ReHo values in the bilateral posterior cerebellum (voxel level P<0.001, cluster-level FWE corrected P<0.05). Decreased rsFC of the right posterior cerebellum-left superior parietal gyrus and left insula were significantly positively associated with pain-related disability (voxel level P<0.001, cluster-level FWE corrected P<0.05). CONCLUSIONS: These findings demonstrated that MCE had superior effects in relieving pain and pain-related disability, which might be associated with its modulation of rsFC between the cerebellum and areas involved in sensory-discriminative processing of noxious and somato-sensory stimuli, affection, and cognition. CLINICAL REHABILITATION IMPACT: This study provided preliminary evidence that MCE might alleviate NCLBP through its modulation of the function of brain areas related to chronic pain and postural control. Those results support MCE's clinical application and help physiotherapists to provide better multidisciplinary interventions with the combination of MCE and other first-line treatments.

Gray Matter Abnormalities in Patients with Chronic Low Back Pain: A Systematic Review and Meta-Analysis of Voxel-Based Morphometry Studies.

BACKGROUND: Numerous studies utilizing voxel-based morphometry (VBM) have documented gray matter (GM) alterations in patients with chronic low back pain (CLBP) compared to healthy controls. However, the inconsistency in GM abnormalities observed across different studies has hindered their potential application as objective neuroimaging biomarkers or therapeutic targets. To address this issue, we conducted a comprehensive meta-analysis of VBM studies to identify robust GM differences between CLBP patients and healthy controls. METHODS: The databases including PubMed, Embase, and Web of Science were systematically searched from January 2000 to September 2022 to identify eligible neuroimaging studies. In this coordinate-based meta-analysis of VBM studies, the Seed-based d Mapping with Permutation of Subject Images method was used to quantitatively assess regional differences in GM between CLBP patients and healthy controls. RESULTS: Thirteen VBM studies, involving a total of 574 CLBP patients and 1239 healthy controls, were included in the meta-analysis. The findings revealed that CLBP patients exhibited increased GM in the left striatum and left postcentral gyrus and decreased GM in the left superior frontal gyrus, left cerebellum, right striatum, left insula, and right middle occipital gyrus compared to healthy controls. The jackknife sensitivity analysis confirmed the robustness of these neuroimaging findings. CONCLUSIONS: This study provides new insights into potential treatment strategies for CLBP and identifies neuroimaging biomarkers for pain chronification. These findings highlight the importance of considering regional GM abnormalities in the development of clinical interventions for CLBP.

Investigating the brain functional abnormalities underlying pain hypervigilance in chronic neck and shoulder pain: a resting-state fMRI study.

PURPOSE: To investigate pain hypervigilance in individuals suffering from chronic neck and shoulder pain (CNSP) and its underlying brain mechanism. METHODS: The evaluation of pain vigilance was conducted through the utilization of pain vigilance and awareness questionnaires. Voxel-wise regional homogeneity (ReHo) from 60 CNSP patients and 60 healthy controls (HCs) using resting-state fMRI data. Voxel-wise two-sample T-test was conducted to reveal the ReHo variations between CNSP and HC. Correlation analyses were utilized to reveal the connection between brain abnormalities and medical measurements. Furthermore, a mediation analysis was conducted to elucidate the pathway-linking changes in brain function with medical measurements. RESULTS: Our present study revealed three main findings. Firstly, patients with CSNP demonstrated a heightened vigilance of pain in comparison to healthy adults, a common occurrence among individuals with chronic pain conditions. Secondly, we observed brain abnormalities in various brain regions in CSNP patients, and these alterations were associated with the extent of pain vigilance. Lastly, the pain hypervigilance impact on the severity of pain was found to be controlled by regional neural activity in the anterior cingulate cortex (ACC) in subjects with CSNP. CONCLUSION: Our findings suggested that long-term repetitive nociceptive input caused by chronic pain further aggravates the pain intensity by impairing the vigilance-related pain processing within the anterior cingulate cortex in CNSP patients.

Probable chronic pain, brain structure, and Alzheimer's plasma biomarkers in older men.

Chronic pain leads to tau accumulation and hippocampal atrophy in mice. In this study, we provide one of the first assessments in humans, examining the associations of probable chronic pain with hippocampal volume, integrity of the locus coeruleus (LC)-an upstream site of tau deposition-and Alzheimer's Disease-related plasma biomarkers. Participants were mostly cognitively unimpaired men. Probable chronic pain was defined as moderate-to-severe pain in 2+ study waves at average ages 56, 62, and 68. At age 68, 424 participants underwent structural magnestic resonance imaging (MRI) of hippocampal volume and LC-sensitive MRI providing an index of LC integrity (LC contrast-to-noise ratio). Analyses adjusted for confounders including major health conditions, depressive symptoms, and opioid use. Models showed that men with probable chronic pain had smaller hippocampal volume and lower rostral-middle-but not caudal-LC contrast-to-noise ratio compared to men without probable chronic pain. Men with probable chronic pain also had higher levels of plasma total tau, beta-amyloid-42, and beta-amyloid-40 compared to men without probable chronic pain. These findings suggest that probable chronic pain is associated with tau accumulation and reduced structural brain integrity in regions affected early in the development of Alzheimer's Disease. PERSPECTIVE: Probable chronic pain was associated with plasma biomarkers and brain regions that are affected early in Alzheimer's disease (AD). Reducing pain in midlife and elucidating biological mechanisms may help to reduce the risk of AD in older adults.

Gray Matter Adaptations to Chronic Pain in People with Whiplash-Associated Disorders are Partially Reversed After Treatment: A Voxel-based Morphometry Study.

Gray matter (GM) changes are often observed in people with chronic spinal pain, including those with chronic whiplash-associated disorders (CWAD). These GM adaptations may be reversed with treatment, at least partially. Pain neuroscience education combined with exercise (PNE+Exercise) is an effective treatment, but its neural underlying mechanisms still remain unexplored in CWAD. Here, we performed both cross-sectional and longitudinal voxel-based morphometry to 1) identify potential GM alterations in people with CWAD (n = 63) compared to age- and sex-matched pain-free controls (n = 32), and 2) determine whether these GM alterations might be reversed following PNE+Exercise (compared to conventional physiotherapy). The cross-sectional whole-brain analysis revealed that individuals with CWAD had less GM volume in the right and left dorsolateral prefrontal cortex and left inferior temporal gyrus which was, in turn, associated with higher pain vigilance. Fifty individuals with CWAD and 29 pain-free controls were retained in the longitudinal analysis. GM in the right dorsolateral prefrontal cortex increased after treatment in people with CWAD. Moreover, the longitudinal whole-brain analysis revealed that individuals with CWAD had decreases in GM volumes of the left and right central operculum and supramarginal after treatment. These changes were not specific to treatment modality and some were not observed in pain-free controls over time. Herewith, we provide the first evidence on how GM adaptations to CWAD respond to treatment. PERSPECTIVE: This article presents which gray matter adaptations are present in people with chronic pain after whiplash injuries. Then, we examine the treatment effect on these alterations as well as whether other neuroplastic effects on GM following treatment occur.