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Abstract Background Neuroinflammation, mediated by the activation of microglia, contributes to central sensitization, which is associated with the development of chronic migraine (CM). TREM1 receptors amplify the inflammatory response. However, their relationship to CM is unclear. Thus, this study endeavoured to elucidate the exact role of TREM1 in CM. Methods Nitroglycerin (NTG) was repeatedly administered intraperitoneally to establish the CM model. Mechanical and thermal sensitivities were assessed using von Frey filaments and hot plate assays. Using Western blotting, TREM1, NF-κB pathway, NLRP3 inflammasome components, and proinflammatory cytokines were all detected. Immunofluorescence was used to examine the cellular distribution of TREM1 and NLRP3, the number of microglia, immunoreactivity, and morphological changes. We examined the effects of TREM1 antagonists (LR12) and NF-κB inhibitors (PDTC) on pain behaviour, as well as the production of c-fos and CGRP. Additionally, we investigated whether LR12 and PDTC affect the activation of microglia and the NLRP3 inflammasome. We synthesized siRNA and TREM1-overexpressing plasmids to transfect BV2 cells treated with LPS and normal BV2 cells and treated TREM1-overexpressing BV2 cells with PDTC. The NF-κB pathway, NLRP3 inflammasome components, and proinflammatory cytokines were quantified using Western blotting. Results Following NTG administration, the expression of TREM1 was significantly upregulated and exclusively localized in microglia in the TNC, and was well co-localized with NLRP3. Furthermore, activation of the classical NF-κB pathway was observed. Pre-treatment with LR12 and PDTC effectively attenuated mechanical hypersensitivity, suppressed the expression of c-fos and CGRP, and inhibited NF-κB activity in CM mice. Additionally, inhibition of TREM1 and NF-κB activity mitigated NTG-induced microglia and NLRP3 activation, as well as proinflammatory cytokines production. In vitro, knockdown of TREM1 resulted in attenuated activation of the NF-κB pathway following lipopolysaccharide (LPS) treatment and reduced expression of NLRP3 inflammasome components as well as proinflammatory cytokines. After TREM1 overexpression, the NF-κB pathway was activated, NLRP3 inflammasome components and proinflammatory cytokines were upregulated, and PDTC reversed this phenomenon. Conclusions Our findings suggest that TREM1 regulates microglia and NLRP3 activation via the NF-κB pathway, thereby contributing to central sensitization and implicating its involvement in chronic migraine pathogenesis.

Abstract Up to 50% of women will develop pelvic organ prolapse (POP) over their lifetime. Symptoms include pain, bulge, urinary, bowel and sexual symptoms affecting all aspects of a woman’s life. Many women with POP symptoms present initially to primary care settings. Research has shown these interactions are often unsatisfactory, with women reporting their health care professional (HCP) trivialized their symptoms or appeared to have poor knowledge about pelvic floor dysfunction (PFD). Aim The aim of this qualitative study was to explore experiences of younger women seeking treatment for POP and their recommendations for improvements. Methods Ethics approval was obtained (LS-21-01-Carroll-Ful). Women with POP were recruited from an online support group (n = 930 members). Inclusion criteria: adult women, diagnosed with POP and aware of their POP stage. Following informed consent, a demographic questionnaire, interview questions and the Central Sensitization Inventory (CSI) were forwarded. Semi-structured zoom audio-recorded interviews were conducted. Thematic analysis was undertaken; transcripts coded, and themes identified. Results Fourteen women aged 32–41, parity 1–3, with POP Grade 1–3 participated. Many women reported HCPs as dismissive or not appreciative of the impact of their condition. Others described interactions with HCPs who they felt listened, understood the impact of their POP, gave simple explanations, a positive prognosis and outlined a realistic treatment plan. Current antenatal education, post-partum care and primary HCP screening for PFD were identified by women as deficient. Many highlighted delays in accessing specialist care for POP. Women made several recommendations for improvements to the current model of care. Conclusions Increased focus on person-centred care, particularly emotional support, information and education may improve younger women’s experiences when seeking care for POP.

Introduction Despite the acknowledged interconnection between smoking and pain, research on the relationship between smoking and central sensitization (CS) is scarce; this pain mechanism has attracted recent research attention. Considering potential sex differences, this cross-sectional study aimed to investigate the association between smoking and CS. Material and Methods Overall, 415 adult participants from an outpatient clinic underwent evaluation. The analysis focused on determining the relationship between smoking status and CS by differentiating between sexes. Data were collected on smoking presence or absence (independent variable) and CS (dependent variable) for each sex, with age, education level, drinking history, depression, and anxiety as covariates. CS was evaluated using the Central Sensitization Inventory. Following a descriptive analysis of the study population’s characteristics, logistic regression analysis was employed to assess the relationships. Results The average participant age was 42.3 years, with 59% being women. Among women, a significant association was found between smoking status and higher CS severity (AOR=3.21; 95% CI 1.29–7.99, p

Beibei Feng,1– 4,* Chen Gong,1,3,4,* Longfei You,1,3,4,* Yangyang Lin,1,3,4 Yafei Wang,1,3,4 Wing Yuk Ip,2 Yuling Wang1,3,4 1Department of Rehabilitation Medicine, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Orthopaedics & Traumatology, the University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of China; 3Guangdong Provincial Clinical Research Center for Rehabilitation Medicine, Guangzhou, People’s Republic of China; 4Biomedical Innovation Center, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuling Wang, Department of Rehabilitation Medicine, the Sixth Affiliated Hospital, Sun Yat-sen University, No. 26, Yuancun 2nd Cross Road, Guangzhou, 510655, People’s Republic of China, Tel + 86-20-38476737, Fax +86-20-38254221, Email wangyul@mail.sysu.edu.cn Wing Yuk Ip, Department of Orthopaedics & Traumatology, the University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of China, Tel +852-22554581, Fax +852-28174392, Email wyip@hku.hkPurpose: Central sensitization (CS) is commonly seen in chronic pain disorders, including neuropathic pain. However, there exist inconsistencies concerning the presence of CS in chronic pain secondary to carpal tunnel syndrome (CTS). CS and neuropathic pain manifestations in CTS remain not well established. Therefore, this study aims to investigate the CS and pain profiles in patients with CTS and to explore the potential determinants associated with CS.Patients and Methods: Patients with suspected CTS symptoms lasting 3 months or above and healthy controls were enrolled. History, physical examinations, and nerve conduction studies were employed to confirm the diagnosis and severity of median nerve dysfunction. The central sensitization inventory (CSI) was used to screen CS. Other outcomes included neuropathic pain, CTS-specific symptom severity and functions, emotion, and health-related quality of life. Between-group comparisons were conducted in terms of the CS presence. Logistic regression analysis was performed to identify determinants associated with CS.Results: Over 60% of participants with CTS were found with clinical CS, significantly higher than that in the control group. More than 70% of the CTS participants were identified to have possible or very likely neuropathic pain components. In addition, one-fourth of CTS cases had depression or anxiety. Anxiety was associated with an increased risk of developing CS in CTS (adjusted OR=1.31, 95% CI 1.08– 1.59), whereas higher self-perceived general health rating was negatively associated with the presence of CS (adjusted OR=0.92, 95% CI 0.88– 0.97) in the multivariate adjusted regression model.Conclusion: CS is prevalent in patients with CTS. Predominant neuropathic pain characteristics were uncovered in CTS patients as well as comorbid psychological distress. Significant association was found between anxiety and CS presence. Self-perceived general health was inversely related to CS. Further research is warranted to explore the mechanisms of anxiety and central pain processing in painful entrapment neuropathy.Keywords: central sensitization, chronic pain, carpal tunnel syndrome, determinants

Abstract Background This study was conducted to develop a simplified Chinese version of the central sensitization inventory (CSI-CV) and to evaluate its reliability and validity. Methods The CSI-CV was developed through a process involving the translation and back translation of the original CSI. Subsequently, experts reviewed and revised the content of the items to ensure their appropriateness. A total of 325 patients with knee osteoarthritis (KOA), who were scheduled to undergo total knee arthroplasty (TKA), completed the CSI-CV at a prominent orthopedic center in Xi'an, China. Afterward, a random selection of 100 participants was chosen for retesting after one week. The reliability and validity of the inventory were evaluated through exploratory factor analysis, correlation coefficient calculation and other methods. Results The CSI-CV consists of 25 items in five dimensions (emotional distress, headache and jaw symptoms, physical symptoms, urological symptoms, and fatigue and sleep problems). The cumulative variance contribution rate was 75.3%, the Cronbach's α coefficient was 0.83, the Guttman split-half reliability coefficient was 0.88 and the intraclass correlation coefficient was 0.965. The CSI-CV scores correlated moderately with the total scores of the brief pain inventory (r = 0.506), Western Ontario and McMaster Universities Osteoarthritis Index (r = 0.466) and EuroQoL Group's five-dimension questionnaire (r = 0.576). Conclusions The findings demonstrate that the CSI was successfully trans-culturally adapted into a simplified Chinese version (CSI-CV) that was reliable and valid for Chinese-speaking patients who awaiting TKA for KOA.

Background/Objectives: Fibromyalgia (FM) is a syndrome characterized by widespread chronic pain as the primary symptom. Neurophysiological pain mechanisms, such as the function of the descending inhibitory system, are impaired in this condition. The main objective of this study was to compare the results of two paradigms to evaluate CPM in women with FM. The secondary objective was to correlate the results of each CPM paradigm with the clinical status of patients with FM. Methods: One hundred and three FM women were divided into two groups: fifty patients diagnosed with FM were assigned to the conditioned pain modulation (CPM) group using a cold pressor stimulus, and fifty-three patients were assigned to the CPM group using the ischemic pressure stimulus. The main outcome measures were pain intensity, disability, mechanical hyperalgesia, and CPM. Results: The primary analysis revealed significant differences between the results obtained from the different CPM protocols. Poorer outcomes in the cold pressor test correlated with higher pain intensity and a greater disability index. Conclusions: Pain modulation abnormalities in FM patients were evident when using either the cold pressor or ischemic pressure stimuli to establish the CPM paradigm. The cold pressor conditioning stimulus elicited a stronger response than the ischemic pressure stimulus in FM patients.

Background/Objectives: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease characterized by peripheral arthritis, enthesitis, spondylitis and psoriasis. The objective of this study was to examine the prevalence of central sensitization (CS) and its impact on the clinical and functional aspects of PsA. Methods: Adult patients with PsA according to the Classification of Psoriatic Arthritis (CASPAR) criteria were included in this cross-sectional observational study. The Central Sensitization Inventory (CSI) was used to assess the presence of CS. The study evaluated the impact of CS on individuals by analyzing many factors including demographic information, laboratory findings, clinical features, disease activity, quality of life, severity of sleeplessness, frequency of depression and anxiety. The patients were categorized into distinct groups based on the existence and intensity of CS, and a comparative analysis was conducted on their respective outcomes. Results: A total of 103 PsA patients with a mean age of 43.2 (SD: 6.7) years and including 42 (40.8%) males were included. The mean CSI score was 45.4 (SD: 15.1), and 67 (65.1%) patients had CS. The logistic regression analysis revealed that the variables Psoriasis Area Severity Index (PASI), General Anxiety Disorder-7 (GAD-7), and Insomnia Severity Index (ISI) exhibit considerable predictive power in relation to the outcome variable CS (p < 0.05). PASI was observed as the most important variable in predicting CS (OR 9.70 95% CI: 1.52–62.21). Conclusions: CS has demonstrable efficacy in influencing laboratory, clinical, and functional markers among individuals with PsA. When assessing pain sensitivity in these patients, it is important to take into account the presence of CS.

Background: The Pain Sensitivity Questionnaire (PSQ) is a reliable and valid selfreported tool for the assessment of pain sensitivity in clinical practice. The PSQ has been translated, validated, and cross-culturally adapted into multiple languages. However, a validated Arabic version of the PSQ is not available. Thus, this study aims to translate, validate, and cross-culturally adapt the English version of the PSQ into the Arabic language. Methods and materials: The English version of the PSQ was translated and culturally adapted into Arabic following international guidelines. The psychometric properties of the final version of the PSQ-Arabic (PSQ-A) were tested among 119 patients with different persistent musculoskeletal (MSK) pain. Findings: The Cronbach's a for the PSQ-A-total, PSQ-A-moderate, and PSQ-Cminor were 0.81, 0.79, and 0.76, respectively. The means for the PSQ-A-total, PSQ-A-moderate, and PSQ-C-minor scores were 5.07 (±1.28), 5.64 (±2.07), and 4.50 (±0.50). The test-retest reliability measured with the interclass correlation coefficient for 68 subjects was 0.80 for the PSQ-A-total, 0.74 for the PSQ-Amoderate, and 0.77 for the PSQ-A-minor. The PSQ-A-total and the PSQ-Aminor showed positive significant correlations with pain catastrophizing scale (PCS) (r = 0.15, 0.17); P = 0.05), respectively. The PSQ-A-total, PSQ-A-moderate, and PSQ-A-minor showed positive significant correlations with the Brief Pain Inventory (BPI)-pain scores (r = 0.47, 0.43, 0.45; P = 0.01), respectively and with the BPI-pain interference scores (r = 0.37, 0.33, 0.34; P = 0.01), respectively. Conclusions: This study shows that the PSQ-A is a reliable and valid tool to assess individuals with pain sensitivity in Arabic populations. Further studies are recommended to examine the concurrent validity of the PSQ-A against experimental pain sensitivity measures. [ABSTRACT FROM AUTHOR]

Objectives Over 50% of adults living with sickle cell disease (SCD) have chronic pain, but the underlying mechanisms of chronic pain in this population remain unclear. Quantitative sensory testing is an important measurement tool for understanding pain and sensory processing. This scoping review summarizes quantitative sensory testing methodologies used in sickle cell studies and the evidence for central sensitization in this population. Methods We conducted a systematic search of PubMed, Embase, and CINAHL to identify studies using quantitative sensory testing in individuals living with sickle cell disease. Search strategies were based on variations of the terms "sickle cell disease," and "quantitative sensory testing." Eligible studies were observational or experimental studies in human participants living with SCD that reported findings and detailed methodology for at least 1 quantitative sensory testing modality. Results Our search yielded a total of 274 records; 27 of which are included in this scoping review. Of the 27 studies, 17 were original studies (with combined total of 516 adult and 298 pediatric participants), and 10 were secondary or subgroup analyses of these prior studies. Significant variation existed in quantitative sensory testing methodologies across studies, including testing locations, type and intensity of stimuli, and interpretation of findings. Of the identified studies, 22% (2/9 studies) reported sensory abnormalities in mechanical sensitivity and thresholds, 22% (2/9 studies) reported abnormal pressure pain thresholds, 46% (6/13 studies) reported sensory abnormalities in thermal pain thresholds and tolerance (cold and warm), and 50% (2/4 studies) reported abnormalities in temporal summation. Conclusion Future studies should use standardized quantitative sensory testing protocols with consistent and operationalized definitions of sensitization to provide clear insight about pain processing and central sensitization in sickle cell disease. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the prevalence of idiopathic intracranial hypertension (IIH) in fibromyalgia (FMS) patients by utilizing ultrasound to measure the optic nerve sheath diameter (ONSD), a marker of elevated intracranial pressure and also to investigate the relationship with function, fatigue, quality of life (QOL), central sensitization (CS) and neuropathic pain. Methods: The study encompassed 80 female FMS patients and 75 healthy controls. Ultrasound was employed to measure the average ONSD in both groups. Conditions potentially elevating intracranial pressure were ruled out following neurological assessments. Pain (via visual analog scale, VAS), function (revised Fibromyalgia Impact Questionnaire, r‐FIQ), QOL (Short Form‐36, SF‐36), fatigue (fatigue severity scale, FACIT), CS (Central Sensitization Scale), and neuropathic pain (Douleur Neuropathique‐4) were evaluated. Results: The average ONSD was significantly higher in the patient group than the control group. Patients with ONSD >5.5 mm consistent with IIH were categorized as Group 1 (n = 54, 67.5%), while those with a diameter of 5.5 mm and below‐formed Group 2. VAS pain (p =.033) and FIQ‐R scores (p =.033) were significantly higher in Group 1 than Group 2. Headache was found more common in Group 1. Conclusion: This study unveils a substantial occurrence (67.5%) of IIH in FMS patients, suggesting shared pathophysiological mechanisms contributing to symptoms like fatigue, headache, and cognitive dysfunction. Additionally, these findings implicate heightened functional impairment, CS, headache, and fatigue in FMS patients with IIH. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the occurrence of altered central pain modulation in patients with degenerative lumbar diseases (DLDs) and to analyze its association with physical activity (PA) 3 years after lumbar decompression and fusion. Methods: Preoperative assessments of pressure pain thresholds (PPTs), temporal summation (TS), conditioned pain modulation (CPM) and pain were, respectively, recorded in 304 patients. These patients further underwent International Physical Activity Questionnaire (IPAQ) and both pain-related and psychological assessments 3 years post-operation. Results: Preoperatively, the patients had lower PPTs in both local pain and pain-free areas and lower CPM and higher TS in pain-free areas than healthy subjects (P < 0.05). Postoperatively, 53.9% (164/304) patients showed PA below healthy-related thresholds (< 600 MET min/w). Low PA group showed a greater postoperative weight gain and bone loss and a higher postoperative prevalence of both moderate anxiety and marginal depression than high PA group (P < 0.05). All covariates with differences between the high and low PA groups were subjected to multivariate logistic regression, and long preoperative disease duration, low preoperative PPT in pain-free area, high preoperative TS, revision surgery, severe postoperative low back pain and significant postoperative pain catastrophizing thought were independently associated with low postoperative PA (P < 0.05). Conclusions: This study supports the existence of central sensitization (CS) caused by abnormal central pain modulation in DLDs. Pre-existing CS in these patients may be associated with low PA after lumbar surgeries, and this low-activity lifestyle may predispose patients to multiple adverse health outcomes. Preoperative dynamic quantitative sensory testing may provide information for the identification of at-risk patients. [ABSTRACT FROM AUTHOR]

Objective. To investigate the prevalence of central sensitization (CS) in patients with psoriatic arthritis (PsA) and its association with disease activity and patient-reported outcome measures. Methods. This cross-sectional study included adults with PsA without coexisting fibromyalgia (FM). Patients underwent a clinimetric assessment to collect variables regarding disease activity, quality of life (QOL), functional ability, impact of disease, and CS. Spearman ρ was used to examine the relationship between CS Inventory (CSI) scores and other variables. A multivariate analysis was performed to determine the independent contribution of each variable to the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) score. Results. One hundred fifty-seven patients were enrolled. Of them, 45.2% scored a CSI ≥ 40, indicating a high probability of CS. Significant correlations were found between CSI and disease activity, as evaluated by Disease Activity in Psoriatic Arthritis score and Psoriatic Arthritis Disease Activity Score (ρ 0.587 and ρ 0.573, respectively), between CSI and the Health Assessment Questionnaire (ρ 0.607), and between CSI and the 36-item Short Form Health Survey physical component summary and mental component summary scores (ρ -0.405 and ρ -0.483, respectively). In multivariate analysis, CSI score was the principal independent variable (P < 0.001) contributing to PsAID-12 score. Conclusion. Patients with PsA with symptoms of CS had higher disease activity, worse functional ability, and worse QOL. The presence of CS is the major contributor in the impact of disease. [ABSTRACT FROM AUTHOR]

Cluster Headache (CH) is a primary headache that causes severe pain. Some evidence suggests that central mechanisms might be involved. The objective of this study was (1) to compare hyperalgesia signs, temporal summation and conditioned pain modulation among episodic (ECH) and chronic CH (CCH) patients and controls, (2) to compare these factors between sides in the patient groups and (3) to compare the psychophysical variables between the groups. This cross-sectional study included 71 subjects divided into three groups (ECH, CCH and controls). Pressure pain thresholds, temporal summation, conditioned pain modulation and other psychosocial variables were measured. The ANOVA showed differences for all physical outcome measures (p < 0.05). Bonferroni post hoc analyses showed differences when comparing the patient groups with the healthy subjects (p < 0.05), with large effect sizes (d > 0.8). No differences between the patient groups were found for almost all the variables (p > 0.05). Significant differences for all the variables were detected when comparing the symptomatic and non-symptomatic sides in both the ECH and CCH groups (p < 0.05). The ECH and CCH groups showed mechanical hyperalgesia, increased temporal summation and impaired inhibitory mechanisms compared to the controls. Side-to-side differences were also detected within the patient groups. Patients with CCH had poorer sleep quality and quality of life than the controls. [ABSTRACT FROM AUTHOR]

In chronic migraine with medication overuse (CM-MOH), sensitization of visual cortices is reflected by (i) increased amplitude of stimulus-evoked responses and (ii) habituation deficit during repetitive stimulation. Both abnormalities might be mitigated by inhibitory transcranial neurostimulation. Here, we tested an inhibitory quadripulse repetitive transcranial magnetic stimulation (rTMS-QPI) protocol to decrease durably visual cortex excitability in healthy subjects (HS) and explored its therapeutic potential in CM-MOH patients. Pattern-reversal visual evoked potentials (VEP) were used as biomarkers of effect and recorded before (T1), immediately after (T2), and 3 h after stimulation (T3). In HS, rTMS-QPI durably decreased the VEP 1st block amplitude (p < 0.05) and its habituation (p < 0.05). These changes were more pronounced for the P1N2 component that was modified already at T2 up to T3, while for N1P1 they were significant only at T3. An excitatory stimulation protocol (rTMS-QPE) tended to have an opposite effect, restricted to P1N2. In 12 CM-MOH patients, during a four-week treatment (2 sessions/week), rTMS-QPI significantly reduced monthly headache days (p < 0.01). In patients reversing from CM-MOH to episodic migraine (n = 6), VEP habituation significantly improved after treatment (p = 0.005). rTMS-QPI durably decreases visual cortex responsivity in healthy subjects. In a proof-of-concept study of CM-MOH patients, rTMS-QPI also has beneficial clinical and electrophysiological effects, but sham-controlled trials are needed. [ABSTRACT FROM AUTHOR]

Background: Physical exercise is an important element in the rehabilitation of chronic whiplash-associated disorders, with the physiological process underlying pain reduction called exercise-induced hypoalgesia. In chronic whiplash-associated disorders, exercise-induced hypoalgesia appears impaired, and the research suggests a relationship with symptoms of dysfunctional nociceptive processing, such as central sensitization. This study improves our understanding of exercise-induced hypoalgesia in chronic whiplash-associated disorders by examining the differences between the extent of exercise-induced hypoalgesia in subgroups based on scores on the central sensitization inventory (CSI). Methods: Data were collected from 135 participants with chronic whiplash-associated disorders who completed a set of questionnaires. Pain pressure thresholds and temporal summations were assessed before and after a submaximal aerobic bicycle exercise test. Results: We observed no interaction effect between exercise-induced hypoalgesia and the CSI scores for both pain pressure threshold and temporal summation. No overall statistical effect was measured in the analysis of the effect of time. The pain pressure threshold significantly related to the CSI. The temporal summation showed no correlation. Conclusions: During this study, we did not find evidence for a difference in the presence of exercise-induced hypoalgesia when the subgroups were created based on the central sensitization cluster calculator. Limited evidence was found for the influence of CSI scores on the delta pain pressure threshold. [ABSTRACT FROM AUTHOR]

The diagnostic criteria for fibromyalgia (FM) have relied heavily on subjective reports of experienced symptoms coupled with examination-based evidence of diffuse tenderness due to the lack of reliable biomarkers. Rheumatic disorders that are common causes of chronic pain such as rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and chronic low back pain are frequently found to be comorbid with FM. As a result, this can make the diagnosis of FM more challenging. We aim to develop a reliable classification algorithm using unique spectral profiles of portable FT-MIR that can be used as a real-time point-of-care device for the screening of FM. A novel volumetric absorptive microsampling (VAMS) technique ensured sample volume accuracies and minimized the variation introduced due to hematocrit-based bias. Blood samples from 337 subjects with different disorders (179 FM, 158 non-FM) collected with VAMS were analyzed. A semi-permeable membrane filtration approach was used to extract the blood samples, and spectral data were collected using a portable FT-MIR spectrometer. The OPLS-DA algorithm enabled the classification of the spectra into their corresponding classes with 84% accuracy, 83% sensitivity, and 85% specificity. The OPLS-DA regression plot indicated that spectral regions associated with amide bands and amino acids were responsible for discrimination patterns and can be potentially used as spectral biomarkers to differentiate FM and other rheumatic diseases. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation, mediated by the activation of microglia, contributes to central sensitization, which is associated with the development of chronic migraine (CM). TREM1 receptors amplify the inflammatory response. However, their relationship to CM is unclear. Thus, this study endeavoured to elucidate the exact role of TREM1 in CM. Methods: Nitroglycerin (NTG) was repeatedly administered intraperitoneally to establish the CM model. Mechanical and thermal sensitivities were assessed using von Frey filaments and hot plate assays. Using Western blotting, TREM1, NF-κB pathway, NLRP3 inflammasome components, and proinflammatory cytokines were all detected. Immunofluorescence was used to examine the cellular distribution of TREM1 and NLRP3, the number of microglia, immunoreactivity, and morphological changes. We examined the effects of TREM1 antagonists (LR12) and NF-κB inhibitors (PDTC) on pain behaviour, as well as the production of c-fos and CGRP. Additionally, we investigated whether LR12 and PDTC affect the activation of microglia and the NLRP3 inflammasome. We synthesized siRNA and TREM1-overexpressing plasmids to transfect BV2 cells treated with LPS and normal BV2 cells and treated TREM1-overexpressing BV2 cells with PDTC. The NF-κB pathway, NLRP3 inflammasome components, and proinflammatory cytokines were quantified using Western blotting. Results: Following NTG administration, the expression of TREM1 was significantly upregulated and exclusively localized in microglia in the TNC, and was well co-localized with NLRP3. Furthermore, activation of the classical NF-κB pathway was observed. Pre-treatment with LR12 and PDTC effectively attenuated mechanical hypersensitivity, suppressed the expression of c-fos and CGRP, and inhibited NF-κB activity in CM mice. Additionally, inhibition of TREM1 and NF-κB activity mitigated NTG-induced microglia and NLRP3 activation, as well as proinflammatory cytokines production. In vitro, knockdown of TREM1 resulted in attenuated activation of the NF-κB pathway following lipopolysaccharide (LPS) treatment and reduced expression of NLRP3 inflammasome components as well as proinflammatory cytokines. After TREM1 overexpression, the NF-κB pathway was activated, NLRP3 inflammasome components and proinflammatory cytokines were upregulated, and PDTC reversed this phenomenon. Conclusions: Our findings suggest that TREM1 regulates microglia and NLRP3 activation via the NF-κB pathway, thereby contributing to central sensitization and implicating its involvement in chronic migraine pathogenesis. [ABSTRACT FROM AUTHOR]

BackgroundObjectiveMethodsResultsConclusionPatellofemoral pain (PFP) is a common multifactorial condition in young and physically active people.The occurrence of central sensitization may play an important role in sensory disturbance. This study was designed to investigate, in patients with chronic PFP, the presence of disturbances in tactile acuity with central sensitization.Thirty patients with chronic PFP and 30 matched healthy controls entered this cross-sectional study. Graphesthesia (numerical score), two-point discrimination (mm), and point-to-point sensation (mm) were assessed in all participants.The results of between-group comparisons showed that there were significant differences between the involved knee in patients with chronic PFP and healthy participants in graphesthesia (median = 13 [case], 19 [control]; p < .001), two-point discrimination (median = 25.8 [case], 20.3 [control]; p < .001), and point-to-point sensation (median = 14.5 [case], 6.2 [control]; p < .001). There was also a significant difference in graphesthesia between the non-involved knee in patients with chronic PFP and healthy participants (median = 17 [case], 19 [control]; p = .003). The results of within-group comparisons revealed a significant difference in graphesthesia, two-point discrimination, and point-to-point sensation between the involved and non-involved knee in patients with chronic PFP (p < .001). Moreover, there was a positive correlation between two-point discrimination and pain in patients with chronic PFP (r = 0.446, p = .014).The findings of this study reveal that there is a sensory deficit in patients with chronic PFP. Because sensory information is necessary for motor control and pain perception, we can assume that clinical symptoms in these patients are related to sensory deficits. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to determine the effect that different tDCS protocols have on pain processing in healthy people, assessed using quantitative sensory tests (QST) and evoked pain intensity. Methods: We systematically searched in EMBASE, CINAHL, PubMed, PEDro, PsycInfo, and Web of Science. Articles on tDCS on a healthy population and regarding QST, such as pressure pain thresholds (PPT), heat pain thresholds (HPT), cold pain threshold (CPT), or evoked pain intensity were selected. Quality was analyzed using the Cochrane Risk of Bias Tool and PEDro scale. Results: Twenty-six RCTs were included in the qualitative analysis and sixteen in the meta-analysis. There were no significant differences in PPTs between tDCS and sham, but differences were observed when applying tDCS over S1 in PPTs compared to sham. Significant differences in CPTs were observed between tDCS and sham over DLPFC and differences in pain intensity were observed between tDCS and sham over M1. Non-significant effects were found for the effects of tDCS on HPTs. Conclusion: tDCS anodic over S1 stimulation increases PPTs, while a-tDCS over DLPFC affects CPTs. The HPTs with tDCS are worse. Finally, M1 a-tDCS seems to reduce evoked pain intensity in healthy subjects. [ABSTRACT FROM AUTHOR]

Chronic pain is sustained, in part, through the intricate process of central sensitization (CS), marked by maladaptive neuroplasticity and neuronal hyperexcitability within central pain pathways. Accumulating evidence suggests that CS is also driven by neuroinflammation in the peripheral and central nervous system. In any chronic disease, the search for perpetuating factors is crucial in identifying therapeutic targets and developing primary preventive strategies. The brain-derived neurotrophic factor (BDNF) emerges as a critical regulator of synaptic plasticity, serving as both a neurotransmitter and neuromodulator. Mounting evidence supports BDNF's pro-nociceptive role, spanning from its pain-sensitizing capacity across multiple levels of nociceptive pathways to its intricate involvement in CS and neuroinflammation. Moreover, consistently elevated BDNF levels are observed in various chronic pain disorders. To comprehensively understand the profound impact of BDNF in chronic pain, we delve into its key characteristics, focusing on its role in underlying molecular mechanisms contributing to chronic pain. Additionally, we also explore the potential utility of BDNF as an objective biomarker for chronic pain. This discussion encompasses emerging therapeutic approaches aimed at modulating BDNF expression, offering insights into addressing the intricate complexities of chronic pain. [ABSTRACT FROM AUTHOR]

Central sensitization (CS) is defined as increased responsiveness of nociceptive neurons in the central nervous system to normal or subthreshold afferent input. The CS phenomenon is caused by continuous, intense nociceptor inputs triggering a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in the central nociceptive pathway. Most patients undergoing surgery for lumbar spinal stenosis (LSS) experience symptoms for more than three months; therefore, it is possible that CS is associated with postoperative symptoms of LSS. The aim of this study was to clarify the influence of CS in patients who underwent surgery for LSS. We used the Central Sensitization Inventory (CSI) to evaluate CS preoperatively. Clinical and neurological symptoms were assessed before surgery and three months after surgery using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOA-BPEQ) and the Oswestry Disability Index (ODI). To evaluate the correlation between the preoperative CSI score and each parameter of the JOA-BPEQ before and three months after surgery, a Pearson correlation coefficient was used. We also evaluated the correlation between preoperative CSI and improvement scores for each parameter of the JOA-BPEQ for surgery. Similarly, the ODI was assessed. This study included 118 patients. After surgery, the parameters of lumbar function disorder, social life function disorder, and mental health disorder revealed a statistically significant relationship (r = −0.289, −0.0354, and −0.493, respectively). There was no significant correlation between CSI and improvement scores of the JOA-BPEQ. The ODI assessment after surgery revealed a statistically significant relationship (r = 0.344). There was no significant correlation between the CSI and ODI improvement scores. This study showed that the severity of the CSI influenced the postoperative outcomes, and that surgical treatment improved the symptoms of LSS regardless of the occurrence of CS preoperatively. [ABSTRACT FROM AUTHOR]

Objective Greater preoperative depression, anxiety, and pain catastrophizing are associated with more severe long-term pain following total knee arthroplasty (TKA). In a secondary analysis of previously reported data, we tested the hypothesis that these associations are mediated by oxidative stress (OS). Design A mixed between/within-subjects longitudinal cohort design. Setting A single academic medical center. Subjects Osteoarthritis patients (n  = 91; 62.6% female) undergoing unilateral TKA. Methods We assessed depression, anxiety, and catastrophizing, as well as markers of central sensitization (widespread pain, temporal summation of pain) preoperatively. Blood samples were then obtained immediately prior to intraoperative tourniquet placement for quantification of in vivo biomarkers of systemic OS, F2-isoprostanes and isofurans. Post-TKA pain intensity (numeric rating scale worst pain [NRS], McGill Pain Questionnaire-2 [MPQ-2]) and function (PROMIS Pain Interference) were assessed at 6 months following TKA. Results Greater preoperative depression, catastrophizing, and widespread pain were associated with higher intraoperative combined OS (F2-isoprostanes+isofurans/2), which was in turn associated with higher post-TKA pain intensity and worse function (P  < .05). All preoperative phenotype predictors except anxiety were correlated positively with post-TKA pain and/or function (P  < .05). Bootstrapped mediation analyses revealed significant (P  < .05) indirect (mediated) effects of depression (NRS Worst Pain, MPQ-2, PROMIS Pain Interference), anxiety (MPQ-2, PROMIS Pain Interference), and catastrophizing (PROMIS Pain Interference) on adverse long-term post-TKA outcomes via elevated OS. Central sensitization-related predictors demonstrated only direct effects (P  < .05) on post-TKA outcomes that were independent of OS mechanisms. Conclusions Results suggest that the adverse impact of depression, anxiety, and pain catastrophizing on post-TKA pain and functional outcomes are mediated in part by elevated OS. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sleep quality in patients with chronic low back pain (CLBP) may affect quality of life (QoL), possibly due to worsening pain, central sensitization (CS), and cognitive factors. However, causal relationship among the factors has not been confirmed yet. OBJECTIVE: The purpose of this study was to test the hypothesis that sleep quality in patients with CLBP is attributable to pain, cognitive factors, and CS, and influences QoL, by structural covariance analysis. METHODS: This is a cross-sectional study. Participants were recruited from six health care facilities and 101 patients with CLBP were included. Structural covariance analysis assessed the fit of data to the model using goodness of fit index (GFI), adjusted goodness of fit index (AGFI), comparative fit index (CFI), and mean squared approximation error (RMSEA). RESULTS: The structural covariance analysis showed that the goodness-of-fit indices were high (GFI = 0.993, AGFI = 0.964, CFI = 1.00, RMSEA < 0.01). Sleep quality was not directly influenced by QoL but rather by CS and cognitive factors. CONCLUSION: This study suggests that sleep quality in patients with CLBP is indirectly mediated through multiple pathways, including cognitive factors and CS, which may influence QoL. [ABSTRACT FROM AUTHOR]

Temporomandibularjoint dysfunction interferes with the quality of life and activities of daily living among patients. The symptoms of temporomandibular dysfunction, including pain and clicking and popping sounds, are worsened during stressful events, and patients report increased pain around the temporomandibular joint. Stress-related behaviors, such as teeth clenching and teeth grinding, are commonly reported as increasing during stress. The prevalence of temporomandibular dysfunction and stress-related behaviors is reported differently in the literature. Stress in higher education is common. The purpose of this pilot study was to investigate the prevalence of temporomandibular joint dysfunction and stress-related behaviors among staff members at a local University. The study also sought to explore pain patterns described by people experiencing temporomandibular joint dysfunction and the relationship between stress-related behaviors and pain symptoms experienced. Further, the impact of stress on symptoms experienced by people with temporomandibular dysfunction was investigated in this pilot study. [ABSTRACT FROM AUTHOR]

According to consistent epidemiological data, the slope of the incidence curve of endometriosis rises rapidly and sharply around the age of 25 years. The delay in diagnosis is generally reported to be between 5 and 8 years in adult women, but it appears to be over 10 years in adolescents. If this is true, the actual onset of endometriosis in many young women would be chronologically placed in the early postmenarchal years. Ovulation and menstruation are inflammatory events that, when occurring repeatedly for years, may theoretically favour the early development of endometriosis and adenomyosis. Moreover, repeated acute dysmenorrhoea episodes after menarche may not only be an indicator of ensuing endometriosis or adenomyosis, but may also promote the transition from acute to chronic pelvic pain through central sensitization mechanisms, as well as the onset of chronic overlapping pain conditions. Therefore, secondary prevention aimed at reducing suffering, limiting lesion progression, and preserving future reproductive potential should be focused on the age group that could benefit most from the intervention, i.e. severely symptomatic adolescents. Early-onset endometriosis and adenomyosis should be promptly suspected even when physical and ultrasound findings are negative, and long-term ovulatory suppression may be established until conception seeking. As nowadays this could mean using hormonal therapies for several years, drug safety evaluation is crucial. In adolescents without recognized major contraindications to oestrogens, the use of very low-dose combined oral contraceptives is associated with a marginal increase in the individual absolute risk of thromboembolic events. Oral contraceptives containing oestradiol instead of ethinyl oestradiol may further limit such risk. Oral, subcutaneous, and intramuscular progestogens do not increase the thromboembolic risk, but may interfere with attainment of peak bone mass in young women. Levonorgestrel-releasing intra-uterine devices may be a safe alternative for adolescents, as amenorrhoea is frequently induced without suppression of the ovarian activity. With regard to oncological risk, the net effect of long-term oestrogen–progestogen combinations use is a small reduction in overall cancer risk. Whether surgery should be considered the first-line approach in young women with chronic pelvic pain symptoms seems questionable. Especially when large endometriomas or infiltrating lesions are not detected at pelvic imaging, laparoscopy should be reserved to adolescents who refuse hormonal treatments or in whom first-line medications are not effective, not tolerated, or contraindicated. Diagnostic and therapeutic algorithms, including self-reported outcome measures, for young individuals with a clinical suspicion of early-onset endometriosis or adenomyosis are proposed. [ABSTRACT FROM AUTHOR]

Objective: Bladder pain syndrome/Interstitial cystitis (BPS/IC) is characterized by increased activity in bladder afferent pathways, recruitment of silent nociceptive neurons, and sensitization of the brain areas responsible for pain amplification. Default mode network (DMN) is a set of regions activated during the resting state, which reflect the brain's intrinsic activity. Conversely, the sensorimotor network (SMN) plays a key role in structural neuroplasticity. This study aimed to evaluate DMN and SMN activity in BPS/IC patients, both with and without bladder noxious stimulus, using functional brain magnetic resonance imaging (MRI). Methods: Six BPS/IC female patients underwent 3 Tesla fMRI brain scanners. Acquisitions consisted of 10-minute blood oxygen level-dependent echo-planar imaging. The first acquisition was with an empty bladder, painless, and the second was with suprapubic pain. Data were processed using the independent component analysis method with the MELODIC tool from the functional brain MRI of the Brain Software Library (FSL). A semi-quantitative analysis was performed afterward. Results: The patients' age was 42.6 ± 5 years, pain intensity was 7 ± 0.7 (0-10), day and night frequency were 9.2 ± 2.2 and 2.8 ± 1.0, and maximal bladder capacity was 260 ± 54 mL. One patient was unable to complete the study. All patients showed a comparable DMN activation in both empty and full bladder states, and all presented high SMN activation whether the bladder was empty or full. Conclusion: The activation of DMN at both bladder states, empty and full, and constant SMN activation without and with pain supports the role of these networks in BPS/IC. Similar findings have been reported in other chronic pain syndromes. [ABSTRACT FROM AUTHOR]

Introduction: Spondyloarthritis (SpA) is a common rheumatic inflammatory disease and can impact patients' work productivity. We aimed to evaluate the impact of pain catastrophizing and central sensitization on work outcomes in young SpA patients and determine the predictive factors of work productivity loss. Material and methods: We performed a cross-sectional study over 6 months. We included patients aged between 18 and 50 years old, diagnosed with axial or peripheral SpA. Pain catastrophizing and central sensitization were assessed using the Pain Catastrophizing Scale (PCS) and Central Sensitization Inventory (CSI) questionnaire, respectively. Impact of SpA on work productivity and activity impairment during and outside of work was measured with the Work Productivity and Activity Impairment Questionnaire (WPAI: Spondyloarthritis). Results: A total of 72 patients were enrolled, with a median age of 39 years (28.3-46), 65.3% men, and 54.4% working patients. Median scores of activity impairment outside of work, and work productivity loss were 50% (40-70), and 50% (40-60), respectively. Median absenteeism and presenteeism scores were 0% (IQR 0-7), and 100% (IQR 86.5-100), respectively. Regarding work-related outcomes: activity impairment was positively correlated with CSI and PCS; presenteeism was significantly associated with male sex (p = 0.009); and work productivity loss was positively associated with anxiety, depression, and poor quality of life. Multivariate regression analysis identified predictive factors of work productivity loss: male sex, poor quality of life, and prolonged morning stiffness. Conclusions: Assessment of the impact of pain catastrophizing and central sensitization on work-related outcomes in patients with SpA is important to understand the burden of illness and to identify early those in need of interventions in clinical practice. [ABSTRACT FROM AUTHOR]

To determine the frequency of spinal segmental sensitization (SSS) syndrome and its association with socioeconomic and educational levels, Depression, smoking, and alcoholism. Analytic cross-sectional study conducted within the time frame of February-August 2022. Outpatient consultation area of the Hospital Regional Universitario de Colima , a public health care institution in Mexico Ninety-eight patients over 18 years of age were selected that presented with chronic musculoskeletal pain of at least 3-month progression (N=98). The patients were initially selected through simple random sampling, complementing 60% of the calculated sample with consecutive cases due to the pandemic status. Not applicable. The subjects gave their informed consent, authorizing the clinical history interview and physical examination that applied the 2019 diagnostic criteria of Nakazato and Romero, as well as the AMAI test, the Mexican National Education System, the Beck Depression Inventory, Fagerstrom Test, and Alcohol Use Disorders Identification Test instrument, to collect the data on socioeconomic and educational levels, Depression, smoking, and alcoholism, respectively. Frequencies and percentages were obtained for the statistical analysis, using the chi-square test, multiple logistic regression, and bivariate/multivariate analyses with the prevalence odds ratio. SSS had a 22.4% frequency and was significantly associated (P<.05) with moderate Depression and severe Depression, signifying that a patient with moderate depression had 5.57 times more probability of presenting with SSS (95% CI, 1.27-30.16, P<.05) , whereas a patient with severe Depression had 8.68 times more probability of presenting with SSS (95% CI, 1.99-47.77, P<.05). The results of the remaining variables were not statistically significant. There is a need for a biopsychosocial focus on SSS, in which the detection of and approach to moderate and severe Depression favors patient awareness of aspects associated with the phenomenon of chronic pain and the creation of coping strategies for that pain. [ABSTRACT FROM AUTHOR]

The phantom tooth pain or Atypical Odontalgia (AO) is a persistent orofacial pain disorder affecting teeth or tooth sockets after dental treatments like root canal therapy or extractions even when there is no any identifiable cause on clinical or radiographic examination. These conditions are thought to be associated with neuropathic, vascular or psychiatric disorders along with comorbid factors like temporomandibular joint dysfunction syndrome, burning mouth syndrome, various types of headaches etc. Peripheral and central sensitization has been considered as a possible pathophysiology of such conditions in denervated teeth and extraction sites. The pain usually radiates from the deafferentation sites to the adjacent structures. These conditions usually get undiagnosed and in most of the scenario, dentists only consider a diagnosis only after failure of multiple invasive treatments and worsening of the symptoms. Although, it is very crucial to establish a diagnostic criteria and treatment regimen for AO, still evidences are confusing and lots of clinicians are still unaware of the condition. Hence, this article reviews on AO, its terminologies, prevalence, chief complain, clinical features, pathophysiology, comorbidities, diagnostic work out, and pharmacological treatment modalities with the aim of describing the clinical characteristics, possible cause and treatment modalities. This will definitely aid in an accurate diagnosis of the conditions, before treatments are initiated to avoid overtreatments in such conditions. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to accurately evaluate pain lasting longer than three months and falls under the category of chronic pain and to determine the risk factors to follow up and treat properly and to develop appropriate diagnostic and treatment algorithms. Patients and methods: Between March 2021 and December 2021, a total of 437 patients (162 males, 275 females; mean age: 44±14.6 years; range, 12 to 82 years) who were referred to the participating centers due to pain complaints and were diagnosed with post-COVID-19 condition according to the criteria defined by the World Health Organization (WHO) were included in the study. The patients were divided into three groups as nociceptive pain, neuropathic pain, and central sensitization, based on the physician's clinical evaluation and the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) and Central Sensitization Inventory scores. Results: The most common diagnosis was nociceptive pain followed by central sensitization. Patients with nociceptive pain had less pain. It was found that not exercising regularly, having a chronic disease and being a woman were risk factors for central sensitization, having thyroid disease before COVID-19, and defining the current pain as very severe were risk factors for neuropathic pain. Conclusion: In the evaluation of post-COVID-19 pain, neuropathic pain and central sensitization should be also considered in addition to nociceptive pain and the severity of pain, systemic diseases and physical activity should be questioned. [ABSTRACT FROM AUTHOR]

Phantom limb pain (PLP) is a challenging condition affecting a significant proportion of amputees. In this article, we describe the case of a 54-year-old Paralympic athlete with phantom limb syndrome following right leg amputation and widespread sports-related enthesitic pain who underwent a whole-body cryostimulation (WBC) cycle, an emerging treatment known for its rapid pain-relieving and anti-inflammatory effects. Assessments were conducted before and after a 10-session WBC cycle, including pain and quality of life assessment and use of medications. A substantial reduction in enthesitic pain, PLP intensity, paresthesia, and tingling related to atmospheric events and improved function and quality of life were reported after the WBC cycle and lasted for two weeks. One month after WBC, the enthesitic pain following sports activity and PLP gradually returned, but with lesser intensity. Similarly, the stump's sensitivity to atmospheric changes returned, but with lower frequency. Pain at night remained lower than before WBC, with significantly improved quality of sleep. This case study suggests that WBC could be a valuable adjuvant treatment for alleviating PLP. Controlled studies are warranted to validate the findings of this case report and elucidate the mechanisms underlying the positive effects of WBC in this condition. [ABSTRACT FROM AUTHOR]

Widespread pain and hyperalgesia are characteristics of chronic musculoskeletal pain conditions, including fibromyalgia syndrome (FM). Despite mixed evidence, there is increasing consensus that these characteristics depend on abnormal pain augmentation and dysfunctional pain inhibition. Our recent investigations of pain modulation with individually adjusted nociceptive stimuli have confirmed the mechanical and thermal hyperalgesia of FM patients but failed to detect abnormalities of pain summation or descending pain inhibition. Furthermore, our functional magnetic resonance imaging evaluations of spinal and brainstem pain processing during application of sensitivity-adjusted heat stimuli demonstrated similar temporal patterns of spinal cord activation in FM and HC participants. However, detailed modeling of brainstem activation showed that BOLD activity during "pain summation" was increased in FM subjects, suggesting differences in brain stem modulation of nociceptive stimuli compared to HC. Whereas these differences in brain stem activation are likely related to the hypersensitivity of FM patients, the overall central pain modulation of FM showed no significant abnormalities. These findings suggest that FM patients are hyperalgesic but modulate nociceptive input as effectively as HC. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to develop a simplified Chinese version of the central sensitization inventory (CSI-CV) and to evaluate its reliability and validity. Methods: The CSI-CV was developed through a process involving the translation and back translation of the original CSI. Subsequently, experts reviewed and revised the content of the items to ensure their appropriateness. A total of 325 patients with knee osteoarthritis (KOA), who were scheduled to undergo total knee arthroplasty (TKA), completed the CSI-CV at a prominent orthopedic center in Xi'an, China. Afterward, a random selection of 100 participants was chosen for retesting after one week. The reliability and validity of the inventory were evaluated through exploratory factor analysis, correlation coefficient calculation and other methods. Results: The CSI-CV consists of 25 items in five dimensions (emotional distress, headache and jaw symptoms, physical symptoms, urological symptoms, and fatigue and sleep problems). The cumulative variance contribution rate was 75.3%, the Cronbach's α coefficient was 0.83, the Guttman split-half reliability coefficient was 0.88 and the intraclass correlation coefficient was 0.965. The CSI-CV scores correlated moderately with the total scores of the brief pain inventory (r = 0.506), Western Ontario and McMaster Universities Osteoarthritis Index (r = 0.466) and EuroQoL Group's five-dimension questionnaire (r = 0.576). Conclusions: The findings demonstrate that the CSI was successfully trans-culturally adapted into a simplified Chinese version (CSI-CV) that was reliable and valid for Chinese-speaking patients who awaiting TKA for KOA. [ABSTRACT FROM AUTHOR]

Background: Chronic spinal pain (CSP) is a major public health problem worldwide, frequently related to sleep problems. Central sensitization (CS) may worsen the clinical picture of CSP patients with insomnia. The aim of this study was to compare self-reported and objectively measured clinical outcomes between insomniac CSP patients with comorbid insomnia with and without symptoms of CS. Methods: A case-control study on baseline self-reported sleep, functioning, and psychological distress through online questionnaires. Objective sleep and physical activity parameters and pressure pain thresholds (PPTs) were assessed through polysomnography, actigraphy, and digital algometry, respectively. Independent sample t-test and Mann–Whitney U tests were used to examine possible differences in the outcome measures between the groups. Results: Data from 123 participants were included and revealed no statistically significant group for objective sleep and physical activity parameters. The CS group, however, presented with worse self-reported sleep (quality sleep, insomnia severity, and dysfunctional beliefs about sleep), increased mental and physical fatigue, and higher psychological distress (anxiety and depressive symptoms), and reported lower PPTs. Conclusions: symptoms of CS may influence perceived sleep and affect functional health and well-being perception but do not seem to affect objective sleep and physical activity. [ABSTRACT FROM AUTHOR]

• High and low frequency stimulation have a different effect on the N13 SEP component. • Dorsal horn excitability changes induced by low frequency stimulation can modulate the N13. • Different experimental models of central sensitization may induce dorsal horn excitability changes through different mechanisms. The N13 component of somatosensory evoked potential (N13 SEP) represents the segmental response of cervical dorsal horn neurons. Neurophysiological studies in healthy participants showed that capsaicin-induced central sensitization causes an increase of the N13 SEP amplitude. Consequently, in human research, this spinal component may serve as a valuable readout of central sensitization. In this study, we wanted to verify if the sensitivity of the N13 SEP for detecting central sensitization is consistent across different experimental pain models inducing central sensitization and secondary hyperalgesia, namely high and low-frequency electrical stimulation (HFS and LFS). In 18 healthy participants, we recorded SEP after bilateral ulnar nerve stimulation before and after secondary hyperalgesia was induced through HFS and LFS applied on the ulnar nerve territory of the hand of one side. The area of secondary hyperalgesia was mapped with a calibrated 128-mN pinprick probe, and the mechanical pain sensitivity with three calibrated 16–64-256-mN pinprick probes. Although both HFS and LFS successfully induced secondary hyperalgesia only LFS increased the amplitude of the N13 SEP. These findings suggest that the sensitivity of the N13 SEP for detecting dorsal horn excitability changes may critically depend on the different experimental pain models. Our results indicate that LFS and HFS could trigger central sensitization at the dorsal horn level through distinct mechanisms, however this still needs confirmation by replication studies. [ABSTRACT FROM AUTHOR]

Purpose: To define the prevalence of Central Sensitization (CS) in patients with Anterior Knee Pain (AKP) and determine whether there is an association between CS and the magnitude of pain, disability, quality-of-life and psychological impairment. Methods: The data of a total of 44 AKP female patients with a mean age of 27.7 years (15–50) recruited consecutively from hospital outpatient knee clinics were prospectively included in this study. The patients had no antecedents of knee trauma or surgery and no history of injury or disease of the nervous system. There were also 50 healthy female controls with a mean age of 26.1 years (16–46). CS was evaluated using the Central Sensitization Inventory (CSI). Quality-of-life was evaluated using the EuroQoL-5D questionnaire. Self-reporting of clinical pain intensity was obtained using the Visual Analogue Scale. The Kujala Knee Scale and IKDC form were used to evaluate disability. Anxiety and depression were evaluated using the Hospital Anxiety and Depression Subscale (HAD). Kinesiophobia was measured with the Tampa Scale for Kinesiophobia (TSK-11) and catastrophizing by means of the Pain Catastrophizing Scale (PCS). Results: Sixteen AKP patients (36%), and 2 (4%) of the healthy controls presented with central sensitization (p < 0.01). AKP patients with CS have a greater degree of disability based on the Kujala Scale and higher levels of anxiety and depression than AKP patients without CS. The score of AKP patients in the CSI correlated weakly with disability and quality of life and moderately with anxiety and depression. However, no association was seen between CSI score and pain intensity, nor with catastrophizing and kinesiophobia. A multivariate logistic regression analysis showed that only depression was statistically significant in the prediction of the presence of CS (odds ratio 1.45; 95% CI 1.07 to 1.96). Conclusions: AKP patients have a significantly higher prevalence of CS in comparison with what has been reported for the general population. This finding suggests the presence of altered pain modulation in a subgroup of AKP patients. Level of evidence: Level III. [ABSTRACT FROM AUTHOR]

Purpose: The impact of central sensitization (CS) on neurological symptoms and surgical outcomes in patients with lumbar spinal stenosis (LSS) remains unknown. This study aimed to investigate the influence of preoperative CS on the surgical outcomes of patients with LSS. Methods: A total of 197 consecutive patients with LSS (mean age 69.3) who underwent posterior decompression surgery with or without fusion were included in this study. The participants completed the CS inventory (CSI) scores and the following clinical outcome assessments (COAs) preoperatively and 12 months postoperatively: the Japanese Orthopaedic Association (JOA) score for back pain, JOA back pain evaluation questionnaire, and Oswestry Disability Index (ODI). The association between preoperative CSI scores and preoperative and postoperative COAs was analyzed, and postoperative changes were statistically evaluated. Results: The preoperative CSI score significantly decreased at 12 months postoperatively and was significantly correlated with all COAs preoperatively and 12 months postoperatively. Higher preoperative CSI showed worse postoperative COAs and inferior postoperative improvement rates in the JOA score, VAS score for neurological symptoms, and ODI. Multiple regression analysis demonstrated that preoperative CSI was significantly associated with postoperative low back pain (LBP), mental health, quality of life (QOL), and neurological symptoms at 12 months postoperatively. Conclusions: Preoperative CS evaluated by CSI had a significantly worse impact on surgical outcomes, including neurological symptoms, disability, and QOL, especially related to LBP and psychological factors. CSI can be used clinically as a patient-reported measure for predicting postoperative outcomes in patients with LSS. [ABSTRACT FROM AUTHOR]

To evaluate the relation of psychosocial parameters and type D personality with central sensitization in knee osteoarthritis (OA). The study included 126 patients with knee OA according to the American College of Rheumatology criteria. Sociodemographic variables (age, gender, education, marital status, annual income), alcohol consumption/smoking, body mass index, comorbidities, and duration of symptoms were noted. Radiographic evaluation was performed according to the Kellgren–Lawrence grading system. The Western Ontario and McMaster Universities Osteoarthritis Index was used for clinical evaluation. Type D personality, negative affectivity, and social inhibition were evaluated using the type D Scale-14 (DS14). Central sensitization was assessed by the central sensitization inventory (CSI), while psychological status, quality of life, and sleep were assessed by the Hospital Anxiety and Depression Scale (HADS), an abbreviated version of the World Health Organization Quality of Life Instrument (WHOQOL-BREF), and the Jenkins Sleep Evaluation Scale (JSS), respectively. The effect of type D personality on study parameters including central sensitization, as well as the risk factors for the development of central sensitization were assessed by regression analyses. Patients with type D personality had higher CSI, HADS scores and lower WHOQOL-BREF scores for psychological health, social relationship, environment and general quality of life. Linear regression analysis showed that the DS14 total score has a significant positive relation with CSI (β = 0.4, p < 0.05), HADS-depression (β = 0.4, p < 0.05), HADS-anxiety (β = 0.5, p < 0.05), and HADS-total scores (β = 0.5, p < 0.05). It also had a significant negative effect on all domains of WHOQOL-BREF (p < 0.05 for all). Logistic regression analysis revealed that JSS [Odds ratio (OR) 0.83, 95% CI 0.73–0.94; p = 0.003] and negative affectivity (OR 0.78, 95% CI 0.65–0.94; p = 0.008) were independent risk factors for the development of central sensitization in knee OA. Type D personality has an impact on quality of life, central sensitization, and psychological health, with negative affectivity and sleep impairment serving as independent risk factors for central sensitization. While managing patients with knee OA, these intimate relationships should be taken into consideration. [ABSTRACT FROM AUTHOR]

Abstract Background Central sensitization (CS) is becoming increasingly recognized as a significant factor in many chronic pain conditions, including knee osteoarthritis (KOA) and chronic low back pain (CLBP). Yet it presently remains unclear how strong is the involvement of CS in KOA and CLBP and which factors are involved in CS in these two chronic disabling diseases. Methods This is a cross-sectional study in which included a total of 178 patients with KOA and 118 patients with CLBP. Inclusion criteria for eligible participants for the KOA group were a confirmed diagnosis of KOA according to the American College of Rheumatology criteria, and for the CLBP group a chronic low back pain for more than 3 months. Subjects were excluded if they presented with a diagnosed psychiatric disorder or if they lacked the capacity to provide informed consent, understand study questionnaires or perform physical performance tests. In each group, were assessed; CS-related symptoms using the Central Sentization Inventory (CSI); demographic and clinical characteristics such as disease duration, pain intensity on a visual analog scale, self-reported function using the Lequesne index for KOA patients and the Oswestry Disability index for CLBP patients, and physical performance with the 6 minutes’ walk test; as well as psychosocial risk factors using the Patient Health Questionnaire for depression (PHQ-9), the Generalized Anxiety Disorder (GAD-7) and the Pain Catastrophizing Scale (PCS). Results CSI scores significantly correlated with pain intensity and disability in KOA and CLBP patients, and were highly correlated with self-reported symptoms of depression, anxiety and pain catastrophizing. Depression significantly predicted the CSI score in both groups. Conclusion These findings provide further evidence for the impact of CS on pain, function and physical performance in KOA and CLBP patients. Psychosocial symptoms such as pain catastrophizing, anxiety and depression should also be considered as they are also associated with CS.

Abstract Background Controversy remains regarding predictors of surgical outcomes for patients with lumbar spinal stenosis (LSS). Pain sensitization may be an underlying mechanism contributing to LSS surgical outcomes. Further, obesity is associated with dissatisfaction and poorer outcomes after surgery for LSS. Therefore, this study aimed to examine the relationship between central sensitization (CS), visceral fat, and surgical outcomes in LSS. Methods Patients with LSS were categorized based on their central sensitization inventory (CSI) scores into low- (CSI

Soichiro Matsuda,1 Yuki Igawa,1,2 Hidekazu Uchisawa,1,2 Shinya Iki,3 Michihiro Osumi1,4 1Graduate School of Health Sciences, Kio University, Nara, Japan; 2Department of Rehabilitation, Nishiyamato Rehabilitation Hospital, Nara, Japan; 3Department of Rehabilitation, Kawaguchi Neurosurgery Rehabilitation Clinic, Osaka, Japan; 4Neurorehabilitation Research Center, Kio University, Nara, JapanCorrespondence: Soichiro Matsuda, Graduate School of Health Sciences, Kio University, 4-2-2 Umaminaka, Kitakatsuragigun, Nara, 635-0832, Japan, Tel +745-54-1601, Fax +745-54-1600, Email f1996957@kio.ac.jpPurpose: In the thermal grill illusion, participants experience a feeling similar to burning pain. The illusion is induced by simultaneously touching warm and cool stimuli in alternating positions. In post-stroke pain, central sensitization is caused by a variety of factors, including damage to the spinothalamic tract and shoulder pain. Because the thermal grill illusion depends on central mechanisms, it has recently been suggested that it may be a useful indicator of central sensitization. Therefore, we hypothesized that post-stroke patients who are more likely to experience central sensitization may also be more likely to experience a thermal grill sensation of pain and discomfort than the likelihood among those who are less likely to experience central sensitization. However, the effects of the thermal grill illusion in post-stroke patients have not yet been reported. In this pilot study, we conducted the thermal grill illusion procedure in post-stroke patients and analyzed the relationship between clinical somatosensory functions and thermal grill sensations. We also conducted brain imaging analysis to identify brain lesion areas that were associated with thermal grill sensations.Patients and Methods: Twenty patients (65.7 ± 11.9 years old) with post-stroke patients participated in this study. The thermal grill illusion procedure was performed as follows: patients simultaneously touched eight water-filled copper bars, with the water temperature adjusted to provide alternate warm (40°C) and cold (20°C) stimuli.Results: Thermal grill sensation of pain and discomfort tended to be associated with the wind-up phenomenon in bedside quantitative sensory testing and thermal grill sensation of discomfort was also related to damage to the thalamic lateral nucleus.Conclusion: These findings suggest that the thermal grill illusion might measure central sensitization, and that secondary brain hyperactivity might lead to increased thermal grill sensations.Keywords: thermal grill illusion, post stroke pain, central sensitization, thalamus, insula

Yoga is an ancient wisdom comprising a multitude of physical and mental practices that are aimed toward a state of optimum physical, mental, social, and spiritual health. Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory nervous system that is often unresponsive to currently available modes of treatment, portending an inferior quality of life for patients. This systematic review and meta-analysis aim to investigate the effect and the potential role of yoga in NP syndromes. PubMed, Scopus, Elton Bryson Stephens Company (EBSCO), and Cochrane Library were screened for randomized controlled trials (RCTs) assessing the effects of yoga in patients on NP. Usual care, no treatment, or any active treatments were acceptable as control interventions. Primary outcome measures were objective or subjective assessment measures of pain intensity. For each outcome, standardized mean differences and 95% confidence intervals (CIs) were calculated. A total of four studies were included for qualitative synthesis. Meta-analysis of three studies revealed an overall effect (Z) in the favor of yoga as an intervention for NP, when compared to controls, although the effect was not statistically significant (three RCTs; Z = 1.10 [P = 0.27]; Heterogeneity: τ2 = 0.37; χ2 = 27.78, df = 2 [P < 0.00001]; I2 = 93%). This review divulged the overall favorable effect of yoga in NP, although it was not statistically significant. It highlights the promising role of yoga on pain intensity and quality of life in NP syndromes while showing that yoga has the advantage of being an inexpensive and easily accessible mode of therapy. Extensive research on the efficiency and safety of yoga must be conducted using robust RCTs with rigorous methodologies.

Context: Evidence suggests that central sensitization (CS) may contribute to pain in osteoarthritis (OA) knee patients, which cannot be treated by locally directed treatment strategies. Aims: The aim of this study was to examine differences in demographic profile of patients with and without central sensitization in osteoarthritis knee. Settings and Design: Observational cross-sectional study at tertiary care hospital. Materials and Methods: The study was conducted in the Department of Physical Medicine and Rehabilitation, VMMC and Safdarjung Hospital in 345 OA knee patients. Demographic profiles including age, gender, education, occupations, type of family, marital and socioeconomic status and central sensitization were assessed. The association between CS and various demographic parameters was investigated. Statistical Analysis Used: Statistical Package for Social Sciences (SPSS) software, IBM manufacturer, Chicago, USA, version 21.0. For statistical significance, P value of less than 0.05 was considered statistically significant. Results: Ninety out of 345 (26%) of study subjects had CS; out of which 96% were females. Younger homemaker and those with unskilled/semiskilled type of job had higher chances of having CS in comparison with those with skilled and professional job (P < .001). Conclusions: Elicitation of specific demographic factors that can predict CS in people with knee OA may help in early identification and management of CS in OA knee patients.

Abigail T Wilson,1,2 Charlotte Razzell,2 William J Hanney1,2 1University of Central Florida, School of Kinesiology and Rehabilitation Sciences, College of Health Professions and Sciences, Orlando, FL, USA; 2Musculoskeletal Research Lab, Institute of Exercise Physiology and Rehabilitation Science, University of Central Florida, Orlando, FL, USACorrespondence: William J Hanney, University of Central Florida, College of Health Professions and Sciences, Division of Physical Therapy, Health Sciences Building I, 12805 Pegasus Drive, Orlando, FL, 32816, USA, Tel +1 407-823-0217, Fax +1 407-823-3464, Email william.j.hanney@ucf.eduPurpose: The Patient Self-Report Survey for the Assessment of Fibromyalgia may potentially be a method for subgrouping patients with musculoskeletal pain who have a nociplastic pain presentation. Limited research has explored the convergent validity of this questionnaire against psychophysical measures of pain sensitivity and psychological factors in individuals with musculoskeletal pain. Therefore, the purpose of this study is to examine the strength of the association between total scores on the Patient Self-Report Survey for the Assessment of Fibromyalgia with clinical, pain sensitivity, and psychological factors.Patients and Methods: As a secondary analysis of a cross-sectional study, participants with shoulder (n = 20) or low back pain (n = 20) completed Quantitative Sensory Testing (QST), pain-related psychological questionnaires, and the Patient Self-Report Survey for the Assessment of Fibromyalgia. A Spearman correlation determined the association between total scores on the Patient Self Report Survey for the Assessment of Fibromyalgia with psychological factors and pain sensitivity behaviorally assessed with QST.Results: Negative psychological factors demonstrate moderate to strong positive associations with the Patient Self-Report Survey for the Assessment of Fibromyalgia (rho range = 0.36– 0.80), suggesting greater negative psychological factors were observed in patients with higher severity of fibromyalgia symptoms. Pain sensitivity factors demonstrated weak to moderate negative associations with The Patient Self-Report Survey for the Assessment of Fibromyalgia (PPT rho range=− 0.36- − 0.41), suggesting that elevated pain sensitivity was observed in individuals with higher severity of nociplastic pain symptoms.Conclusion: Collectively, this supports the convergent validity of the Patient Self-Report Survey for the Assessment of Fibromyalgia with psychological and pain sensitivity factors in patients with musculoskeletal pain.Keywords: pain measurement, pain threshold, nociplastic pain, central sensitization

Abstract Objective To investigate the brain structural correlates of postoperative axial pain (PAP) in degenerative cervical myelopathy (DCM) following posterior cervical decompression surgery. Methods Structural images with high-resolution T1 weighting were collected from 62 patients with DCM and analyzed, in addition to 42 age/gender matched subjects who were healthy. Voxel-based morphometry (VBM) was analyzed, grey matter volume (GMV) was computed. One-way ANOVA was performed to reveal the GMV differences among DCM patients with PAP, patients without PAP and healthy controls (HC). Post-hoc analyses were conducted to identify the pair-wise GMV differences among these three groups. Analyses of correlations were conducted to uncover the link between clinical measurements and GMV variations. Last, support vector machine (SVM) was conducted to test the utility of GMV for classifying PAP and nPAP DCM patients. Results Three main findings were observed: [1] Compared to healthy controls, DCM patients showed a significantly lower GMV in the precuneus preoperatively. DCM patients with PAP also exhibited a lower GMV within precuneus than those without; [2] In DCM patients with PAP, the precuneus GMV was inversely related to the postoperative pain intensity; [3] Moreover, successful classification between PAP and nPAP were observed via SVM based on precuneus GMV as features. Conclusion In summary, our results indicate that precuneus GMV may be linked to PAP in DCM, and could be employed to forecast the emergence of PAP in DCM patients.

Abstract Background Central sensitization is a condition in which even mild stimuli cause pain due to increased neuronal reactivity in the dorsal horn of the spinal cord. It is one of factors of chronic pain in patients with osteoarthritis. However, it is unknown whether central sensitization relates to clinical outcomes after total hip arthroplasty (THA). This study aimed to clarify whether preoperative central sensitization relates to the forgotten joint score-12 (FJS) after THA. Moreover, the secondary outcome was to identify which items in the FJS were most related by central sensitization. Methods This retrospective analysis included 263 hips (263 patients; 51 males and 212 females) that underwent primary THA in our institute and were available for evaluation one year postoperatively. The average patient age was 64.8 ± 11.9 years. The Central Sensitization Inventory (CSI) part A, which is a patient-reported outcome, was used to measure preoperative central sensitization. The correlation between preoperative CSI and postoperative FJS and the association between postoperative FJS and preoperative CSI severity were determined. Moreover, difference in each FJS item was evaluated by CSI severity. Results Twenty-six patients (9.9%) had central sensitization preoperatively. Preoperative CSI scores and postoperative FJS were negatively correlated (r = − 0.331, p

IntroductionMonoaminergic activity modulates nociceptive transmission in the central nervous system (CNS). Although pain is the most disabling symptom of osteoarthritis (OA), limited knowledge exists regarding the CNS mechanisms that amplify pain and drive sensitization processes in humans.ObjectivesThe main objective of this study was to evaluate associations between cerebrospinal fluid (CSF) monoamine metabolites, pain severity, and central sensitization in patients with OA undergoing total hip arthroplasty (THA).MethodsPatients with OA (n = 52) and pain-free controls (n = 30) provided CSF samples for measurement of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), noradrenaline (3-methoxy-4-hydroxyphenylglycol [HMPG]), and dopamine (homovanillic acid [HVA]) monoamine metabolites. Patients with OA completed longitudinal evaluation of pain using clinical measures and quantitative sensory testing.ResultsPatients with OA had higher HMPG levels when compared with controls (P = 0.036). Within patients with OA undergoing THA, higher 5-HIAA and HVA levels were consistently associated with higher preoperative pain severity. Higher concentrations of 5-HIAA and HVA were also associated with lower conditioned pain modulation levels, whereas higher HMPG levels were linked to more efficient conditioned pain modulation. Patients with higher levels of CSF HVA exhibited increased pressure pain sensitivity (arm pressure pain detection threshold < 250 kPa vs ≥ 250 kPa, P = 0.042). Higher preoperative levels of CSF 5-HIAA predicted poorer pain control 6 months postoperatively (brief pain inventory pain severity; adjusted β = 0.010, 95% CI 0.001-0.019).ConclusionsIn OA patients with disabling pain, higher CSF levels of serotonin and dopamine metabolites are associated with increased pain severity and central sensitization. Increased noradrenergic activity may be associated with more efficient pain inhibitory capacity.

Although the pathophysiology of fibromyalgia syndrome has been better understood in recent decades, a unified model of its pathogenesis and an effective therapeutic approach are still far from being realized. The main aim of this article will be to delve into the fundamental mechanisms of the pathophysiology of fibromyalgia conceptualized as stress intolerance syndrome. Using the biopsychosocial model of chronic pain syndromes, we will describe the potential role of the attachment system, C-tactile fibers, and oxytocinergic system dysfunction in the pathophysiology of fibromyalgia syndrome and other central sensitivity syndromes. At the end of the article, the therapeutic implications of this new global and translational pathophysiological model will be briefly discussed.

Neuropathic pain arises from injuries to the nervous system in diseases such as diabetes, infections, toxicity, and traumas. The underlying mechanism of neuropathic pain involves peripheral and central pathological modifications. Peripheral mechanisms entail nerve damage, leading to neuronal hypersensitivity and ectopic action potentials. Central sensitization involves a neuropathological process with increased responsiveness of the nociceptive neurons in the central nervous system (CNS) to their normal or subthreshold input due to persistent stimuli, leading to sustained electrical discharge, synaptic plasticity, and aberrant processing in the CNS. Current treatments, both pharmacological and non-pharmacological, aim to alleviate symptoms but often face challenges due to the complexity of neuropathic pain. Neuromodulation is emerging as an important therapeutic approach for the treatment of neuropathic pain in patients unresponsive to common therapies, by promoting the normalization of neuronal and/or glial activity and by targeting cerebral cortical regions, spinal cord, dorsal root ganglia, and nerve endings. Having a better understanding of the efficacy, adverse events and applicability of neuromodulation through pre-clinical studies is of great importance. Unveiling the mechanisms and characteristics of neuromodulation to manage neuropathic pain is essential to understand how to use it. In the present article, we review the current understanding supporting dorsal root ganglia and spinal cord neuromodulation as a therapeutic approach for neuropathic pain.