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Functional and Neural Correlates Associated with Conditioned Pain Modulation in Patients with Chronic Knee Osteoarthritis Pain: A Cross-Sectional Study.

ABSTRACT: Background: In this study, we aimed to assess the factors that predict a dysfunctional conditioned pain modulation (CPM) in chronic knee OA. Methods: This is a cross-sectional analysis of patients with chronic knee OA from a prospective cohort study in Brazil (n = 85). We performed linear and logistic multivariate regression models using the purposeful selection approach to test the relationship between the CPM in both knees (average) as a dependent variable and demographics, clinical, and neurophysiological as independent variables. Results: A significant negative association between WOMAC pain scores and CPM (β: -0.13) was found. This association was modified by the subjects' race, being stronger in the non-white subjects. In our logistic regression models, pain intensity indexed with the WOMAC pain scale remained a significant association with dichotomized CPM. Furthermore, a significant CPM association with balance, indexed with the Berg Balance score, was evidenced (β: 0.04). Neurophysiological variables showed a significant negative relationship with CPM, such as the relative power of delta oscillations in the frontal area (β: -3.11) and central area (β: -3.23). There was no significant relationship between CPM and the following domains: cognitive, emotion, sleep, opioid receptor polymorphisms, and intrinsic variables of OA disease. There was no association of CPM with TMS-indexed inhibitory markers. Conclusions: These results may indicate that less function of the pain descending inhibitory system in patients with OA is correlated with higher activity-related pain (WOMAC), less balance, and cortical plasticity especially with increased low-frequency (delta) brain oscillations. These associations seem modified by race.

SUBMITTER: Simis M

PROVIDER: S-EPMC10455308 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Functional and Neural Correlates Associated with Conditioned Pain Modulation in Patients with Chronic Knee Osteoarthritis Pain: A Cross-Sectional Study.

Simis Marcel M Pacheco-Barrios Kevin K Vasquez-Avila Karen K Rebello-Sanchez Ingrid I Parente Joao J Castelo-Branco Luis L Marduy Anna A de Melo Paulo S PS Imamura Marta M Battistella Linamara L Fregni Felipe F

Life (Basel, Switzerland) 20230807 8

<b>Background:</b> In this study, we aimed to assess the factors that predict a dysfunctional conditioned pain modulation (CPM) in chronic knee OA. <b>Methods:</b> This is a cross-sectional analysis of patients with chronic knee OA from a prospective cohort study in Brazil (n = 85). We performed linear and logistic multivariate regression models using the purposeful selection approach to test the relationship between the CPM in both knees (average) as a dependent variable and demographics, clini ...[more]

PMID: 37629554

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Project description:ObjectiveTo examine the cross-sectional association of ascending pain mechanisms, implicated in pain sensitization, and descending pain modulation with pain patterns and unpredictability of pain.MethodsThe Multicenter Osteoarthritis Study is a longitudinal cohort of older adults with or at risk of knee osteoarthritis. Peripheral and central ascending pain mechanisms were assessed using quantitative sensory tests, pressure pain thresholds using a handheld pressure algometer (knee/peripheral and wrist/central), and temporal summation using weighted probes (wrist/central). Descending modulation was assessed by conditioned pain modulation using pressure pain thresholds and a forearm ischemia test. Pain patterns were characterized based on responses to the Intermittent and Constant Osteoarthritis Pain questionnaire: 1) no intermittent or constant pain, 2) intermittent pain only, 3) constant pain only, and 4) combined constant and intermittent pain. A question regarding frequency assessed unpredictable pain. We assessed the association of quantitative sensory test measures to pain patterns using regression models with generalized estimating equations.ResultsThere were 2,794 participants (mean age 63.9 years, body mass index 29.5 kg/m2 , and 57% female). Lower pain sensitization by wrist pressure pain threshold (odds ratio [OR] 0.80 [95% confidence interval (95% CI) 0.68, 0.93]) and adequate conditioned pain modulation (OR 1.45 [95% CI 1.10, 1.92]) were associated with having constant ± intermittent pain compared with intermittent pain only. Higher pain sensitization (by pressure pain thresholds and temporal summation) was associated with a higher likelihood of unpredictable pain.ConclusionKnee pain patterns appear to be related to peripheral ± central facilitated ascending pain mechanisms and descending modulatory mechanisms. These findings highlight the need for a broader approach to understanding pain mechanisms by symptomatic disease progression.

Project description:BackgroundPatients with painful knee osteoarthritis (OA) demonstrate hyperalgesia and altered pain-modulatory responses. While some prior work has demonstrated cross-sectional associations between laboratory and clinical pain measures, it is unknown whether individual variability in quantitative sensory testing (QST) responses at baseline can prospectively predict analgesic treatment responses.MethodPatients with knee OA (n = 35) were compared on QST responses to a demographically-matched pain-free control group (n = 39), after which patients completed a month-long treatment study of diclofenac sodium topical gel (1 %), applied up to 4 times daily.ResultsOA patients demonstrated reduced pain thresholds at multiple anatomic sites, as well as reduced conditioned pain modulation (CPM) and enhanced temporal summation of pain. The most pain-sensitive patients tended to report the most intense and neuropathic OA pain. Following diclofenac treatment, the knee OA cohort showed a roughly 30 % improvement in pain, regardless of the presence or absence of neuropathic symptoms. Baseline CPM scores, an index of endogenous pain-inhibitory capacity, were prospectively associated with treatment-related changes in clinical pain. Specifically, participants with higher CPM at baseline (i.e., better functioning endogenous pain-inhibitory systems) showed more reduction in pain at the end of treatment (p < .05).ConclusionsThese results support prior findings of amplified pain sensitivity and reduced pain-inhibition in OA patients. Moreover, the moderate to strong associations between laboratory-based measures of pain sensitivity and indices of clinical pain highlight the clinical relevance of QST in this sample. Finally, the prospective association between CPM and diclofenac response suggests that QST-based phenotyping may have utility in explaining inter-patient variability in long-term analgesic treatment outcomes.Trial registrationClinicalTrials.Gov Identifier: NCT01383954 . Registered June 22, 2011.

Project description:BackgroundIt is estimated that over 240 million people worldwide have osteoarthritis, which is a major contributor to chronic pain and central changes in pain processing, including endogenous pain modulation. The autonomic nervous system plays a crucial role in the pain regulatory process. One of the main mechanisms of remote ischemic conditioning is neuronal signaling from the preconditioned extremity to the heart. This study aims to analyze the acute effect of remote ischemic conditioning on local pain, conditioned pain modulation, and cardiac autonomic control in women with knee osteoarthritis and to see if there is a correlation between them.MethodsWomen more than 50 years with knee osteoarthritis diagnosed according to the American College of Rheumatology criteria in the postmenopausal period will be considered eligible. The study will have blind randomization, be placebo-controlled, and be balanced in a 1:1 ratio. The total of 44 participants will be divided into two groups (22 participants per group): (i) remote ischemic conditioning and (ii) placebo remote ischemic conditioning. Protocol consisting of four cycles of total ischemia, followed immediately by four cycles of 5 min of vascular reperfusion, totaling 40 min. The primary outcomes in the protocol are conditioned pain modulation, which has the pressure pain threshold (kgf/cm2) as its primary outcome measure, and cardiac autonomic modulation, which has the indices found in heart rate variability as its primary outcome measure. Comparisons will be performed using generalized linear mixed models fitted to the data. For correlation, the Pearson or Spearman test will be used depending on the normality of the data. All analyses will assume a significance level of p < 0.05.DiscussionIt is believed that the results of this study will present a new perspective on the interaction between the pain processing system and the cardiovascular system; they will provide the professional and the patient with a greater guarantee of cardiovascular safety in the use of the intervention; it will provide knowledge about acute responses and this will allow future chronic intervention strategies that aim to be used in the clinical environment, inserted in the multimodal approach, for the treatment of osteoarthritis of the knee.Trial registrationClinicalTrials.gov NCT05059652. Registered on 30 August 2021. Last update on 28 March 2023.

Project description:IntroductionHigher physical activity (PA) and lower sedentary behaviour (SB) levels have demonstrated beneficial effects on temporal summation (TS) and conditioned pain modulation (CPM) in healthy adults. This cross-sectional study investigated the relationships between PA and SB and TS/CPM responses in individuals with chronic musculoskeletal pain.MethodsSixty-seven middle-aged and older adults with chronic musculoskeletal pain were recruited from the community. Questionnaires measuring demographics, pain, and psychological measures were completed. Physical activity/SB levels were measured using the International Physical Activity Questionnaire-short form and Sedentary Behaviour Questionnaire, respectively. Semmes monofilament was used to assess mechanical TS (MTS) at the most symptomatic (MTS-S) and a reference region (MTS-R); change in the pain scores (baseline-10th application) was used for analysis. Conditioned pain modulation procedure involved suprathreshold pressure pain threshold (PPT-pain4) administered before and after (CPM30sec, CPM60sec, and CPM90sec) conditioning stimulus (2 minutes; ∼12°C cold bath immersion). For analysis, PPT-pain4 (%) change scores were used.ResultsPPT-pain4 (%) change scores at CPM30sec and CPM60sec demonstrated significant weak positive correlations with SB levels and weak negative correlations with PA measures. After adjusting for confounding variables, a significant positive association was found between SB (h/d) and PPT-pain4 (%) change scores at CPM30sec and CPM60sec. No significant associations between MTS and PA/SB measures.ConclusionSedentariness is associated with higher pain inhibitory capacity in people with chronic musculoskeletal pain. The observed relationship may be characteristic of a protective (sedentary) behaviour to enhance pain modulatory mechanism. Prospective longitudinal studies using objective PA/SB measures are required to validate the observed relationship in a larger sample size.

Project description:ObjectiveMetabolic factors have been shown to be associated to severe radiographic knee osteoarthritis (RKOA). However, more knowledge is needed in early clinical knee osteoarthritis (KOA). The aim was to study associations between metabolic factors and radiographic knee osteoarthritis (OA) in individuals with knee pain. A second aim was to study associations between metabolic factors and RKOA in those with normal BMI and in those overweight/obese, respectively.MethodThis cross-sectional study included 282 individuals with knee pain (without cruciate ligament injury) and aged 30-67 years, and 70% women. Waist circumference, body mass index (BMI), proportion of fat and visceral fat area (VFA) were assessed. RKOA was defined as Ahlbäck grade 1 in at least one knee. Fasting blood samples were taken and triglycerides, cholesterol (total, low density lipoprotein (LDL) and high density lipoprotein (HDL)), C-reactive protein (CRP), glucose, HbA1C were analysed. Metabolic syndrome was defined in accordance with the International Diabetes Federation (IDF). Associations were analysed by logistic regression.ResultsIndividuals with RKOA were older, had higher BMI, higher VFA, larger waist circumference and had increased total cholesterol, triglycerides and LDL-cholesterol, but not fasting glucose. There was no difference between the group with RKOA vs. non-radiographic group regarding the presence of metabolic syndrome. In a subgroup analysis of individuals with normal BMI (n = 126), those with RKOA had higher VFA, more central obesity, higher levels of CRP and total cholesterol, compared with individuals without RKOA. In individuals with obesity, age was the only outcome associated to RKOA.ConclusionThere were clear associations between metabolic factors and RKOA in individuals with knee pain, also in those with normal BMI. In individuals with obesity age was the only variable associated to RKOA.Trial registrationclinicalTrials.gov Identifier: NCT04928170.

Project description:BackgroundDepressive symptoms are a major comorbidity in older adults with knee osteoarthritis (OA). However, the type of activity-induced knee pain associated with depression has not been examined. Furthermore, there is conflicting evidence regarding the association between depression and performance-based physical function. This study aimed to examine (i) the association between depressive symptoms and knee pain intensity, particularly task-specific knee pain during daily living, and (ii) the association between depressive symptoms and performance-based physical function, while considering other potential risk factors, including bilateral knee pain and ambulatory physical activity.MethodsPatients in orthopaedic clinics (n = 95; age, 61-91 years; 67.4% female) who were diagnosed with radiographic knee OA (Kellgren/Lawrence [K/L] grade ≥ 1) underwent evaluation of psychological health using the Geriatric Depression Scale (GDS). Knee pain and physical function were assessed using the Japanese Knee Osteoarthritis Measure (JKOM), 10-m walk, timed up and go (TUG), and five-repetition chair stand tests.ResultsOrdinal logistic regression analysis showed that depression, defined as a GDS score ≥ 5 points, was significantly associated with a worse score on the JKOM pain-subcategory and a higher level of task-specific knee pain intensity during daily living, after being adjusted for age, sex, body mass index (BMI), K/L grade, and ambulatory physical activity. Furthermore, depression was significantly associated with a slower gait velocity and a longer TUG time, after adjusting for age, sex, BMI, K/L grade, presence of bilateral knee pain, and ambulatory physical activity.ConclusionsThese findings indicate that depression may be associated with increased knee pain intensity during daily living in a non-task-specific manner and is associated with functional limitation in patients with knee OA, even after controlling for covariates, including bilateral knee pain and ambulatory physical activity.

Dataset Information

Functional and Neural Correlates Associated with Conditioned Pain Modulation in Patients with Chronic Knee Osteoarthritis Pain: A Cross-Sectional Study.

Publications

Functional and Neural Correlates Associated with Conditioned Pain Modulation in Patients with Chronic Knee Osteoarthritis Pain: A Cross-Sectional Study.

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