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1.
Medicine (Baltimore) ; 103(15): e37786, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38608097

RESUMO

BACKGROUND: Chronic shoulder pain is a common musculoskeletal problem associated with unreleased pain and functional dysfunction that can evolve into central sensitization. Some forms of manual therapy may exacerbate pain and central sensitization. This study investigated the impact of joint position sense therapy (JPST), a moderate joint proprioception training technique, on central sensitization, shoulder functional dysfunction, and pain in patients with chronic shoulder pain compared with more intense exercises or aggressive manual therapies. METHODS: We assessed the pressure pain threshold (PPT) in 30 patients with and 30 patients without chronic shoulder pain. The assessment focused on 4 muscle sites: deltoid, upper trapezius, brachioradialis, and tibialis anterior. Thirty patients with chronic shoulder pain were randomly divided into the JPST and control groups. The JPST group underwent additional shoulder joint position-sense training. The efficiency outcomes were the disabilities of the arm, shoulder, and hand questionnaire, visual analog scale (VAS), and PPT, evaluated at baseline and after the intervention. RESULTS: Significant differences were observed in the PPT values at the brachioradialis (P < .05), deltoid (P < .01), and trapezius (P < .001) among the non-chronic and chronic groups, but not in the tibialis anterior muscle (P > .05). Although both control and JPST interventions effectively improved the disabilities of the arm, shoulder, and hand questionnaire score, pain intensity, and PPT values in the upper limb, the outcomes in the JPST group were significantly different from those in the control group. CONCLUSIONS: Generalized hyperalgesia changes limited to the upper limbs were observed in patients with chronic shoulder pain. JPST has beneficial effects on pain control and functional dysfunction in patients with chronic shoulder pain.


Assuntos
Sensibilização do Sistema Nervoso Central , Dor de Ombro , Humanos , Dor de Ombro/terapia , Extremidade Superior , Manejo da Dor , Propriocepção
3.
Eur J Pharmacol ; 970: 176480, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38490468

RESUMO

The management and therapy of bone cancer pain (BCP) remain formidable clinical challenges. Curcumin and its analogues have been shown to have anti-inflammatory and analgesic properties. In the present study, we investigated the efficacy of curcumin analogue NL04 (NL04) in modulating inflammation in spinal dorsal horn (SDH), thereby exploring its potential to reduce central sensitization of BCP in a rat model. Differing doses of NL04 and curcumin were administered intrathecally either once (on day 12 of BCP) or over seven consecutive days (from day 6-12 of BCP). Results indicated that the ED50 for NL04 and curcumin ameliorating BCP-induced mechanical hyperalgesia is 49.08 µg/kg and 489.6 µg/kg, respectively. The analgesic effects at various doses of NL04 lasted between 4 and 8 h, with sustained administration over a week maintaining pain relief for 1-4 days, while also ameliorating locomotor gait via gait analysis and reducing depressive and anxiety-like behaviors via open-field and light-dark transition tests. The analgesic effects at various doses of curcumin lasted 4 h, with sustained administration over a week maintaining pain relief for 0-2 days. ELISA, Western blotting, qPCR, and immunofluorescence assays substantiated that intrathecal administration of NL04 on days 6-12 of BCP dose-dependently lowered spinal IL-1ß and IL-18 levels and significantly reduced the expression of IKKß genes and proteins, as well as the downstream cleavage of the trans-Golgi network (TGN). Whole-cell patch-clamp results demonstrated that NL04 inhibits potassium ion efflux in rat primary spinal neurons. Thus, NL04 exhibits significant analgesic effects in a BCP rat model by downregulating IKKß expression and inhibiting neuronal potassium ion efflux, which, in turn, suppresses the activation of NLRP3 inflammasomes and reduces IL-1ß production, potentially ameliorating pain management in BCP.


Assuntos
Neoplasias Ósseas , Dor do Câncer , Curcumina , Ratos , Animais , Dor do Câncer/tratamento farmacológico , Dor do Câncer/metabolismo , Curcumina/farmacologia , Curcumina/uso terapêutico , Curcumina/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sensibilização do Sistema Nervoso Central , Quinase I-kappa B/metabolismo , Dor/tratamento farmacológico , Neoplasias Ósseas/complicações , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Analgésicos/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Medula Espinal , Potássio/metabolismo
4.
Int J Rehabil Res ; 47(2): 122-128, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38470712

RESUMO

The aim of the study was to assess the psychometric properties of the Turkish version of Central Sensitization Inventory-9 (CSI-9) in patients with chronic musculoskeletal pain. The methodological study included 92 patients with chronic musculoskeletal pain. The original version of the CSI-9 was translated and culturally adapted into Turkish. The internal consistency and test-retest reliability were evaluated with Cronbach's α and the intraclass correlation coefficient (ICC), respectively. The assessment of reproducibility was conducted with the standard error of measurement (SEM) and minimal detectable difference (MDD) values. Convergent validity was explored by correlation analysis between the CSI-9 and Central Sensitization Inventory (CSI-25), Brief Pain Inventory (BPI), and European Quality of Life Survey-5 Dimensions (EQ-5D). The structural validity was assessed with factor analysis. Floor and ceiling effects were also analyzed. We found a very good internal consistency (Cronbach's α of 0.83) and excellent test-retest reliability (ICC of 0.96) of the Turkish CSI-9. The SEM demonstrated a range between 0.19 and 1.12, and the MDD was observed to vary from 1.17 to 1.35. The CSI-9 correlated significantly with the CSI-25 ( r  = 0.77, P  < 0.001), the pain severity subscale of the BPI ( r  = 0.41 to 0.53, P  < 0.001), the pain interference subscale of the BPI ( r  = 0.21 to 0.58, P  = 0.02 to P  < 0.001), the EQ-5D ( r  = 0.24 to 0.48, P  < 0.05), and the EQ-5D visual analog scale ( r  = -0.41, P  < 0.001). One factor was identified within the CSI-9. Our data suggest that the Turkish CSI-9 is reliable and valid outcome measure for assessing CS in patients with chronic musculoskeletal pain.


Assuntos
Sensibilização do Sistema Nervoso Central , Dor Crônica , Dor Musculoesquelética , Psicometria , Humanos , Masculino , Feminino , Turquia , Dor Musculoesquelética/psicologia , Dor Musculoesquelética/diagnóstico , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilização do Sistema Nervoso Central/fisiologia , Dor Crônica/psicologia , Adulto , Medição da Dor , Qualidade de Vida , Idoso , Traduções , Inquéritos e Questionários
5.
J Headache Pain ; 25(1): 29, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38454376

RESUMO

BACKGROUND: Energy metabolism disorders and neurogenic inflammation play important roles in the central sensitization to chronic migraine (CM). AMP-activated protein kinase (AMPK) is an intracellular energy sensor, and its activation regulates inflammation and reduces neuropathic pain. However, studies on the involvement of AMPK in the regulation of CM are currently lacking. Therefore, this study aimed to explore the mechanism underlying the involvement of AMPK in the central sensitization to CM. METHODS: Mice with recurrent nitroglycerin (NTG)-induced CM were used to detect the expression of AMPK protein in the trigeminal nucleus caudalis (TNC). Following intraperitoneal injection of the AMPK activator 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) and inhibitor compound C, the mechanical pain threshold, activity level, and pain-like behaviors in the mice were measured. The expression of calcitonin gene-related peptide (CGRP) and cytokines, M1/M2 microglia, and NF-κB pathway activation were detected after the intervention. RESULTS: Repeated NTG injections resulted in a gradual decrease in AMPK protein expression, and the negative regulation of AMPK by increased ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression may counteract AMPK activation by increasing ADP/ATP. AICAR can reduce the hyperalgesia and pain-like behaviors of CM mice, improve the activity of mice, reduce the expression of CGRP, IL-1ß, IL-6, and TNF-α in the TNC region, and increase the expression of IL-4 and IL-10. Moreover, AMPK in TNC was mainly located in microglia. AICAR could reduce the expression of inducible NO synthase (iNOS) in M1 microglia and increase the expression of Arginase 1 (Arg1) in M2 microglia by inhibiting the activation of NF-κB pathway. CONCLUSIONS: AMPK was involved in the central sensitization of CM, and the activation of AMPK reduced neuroinflammation in NTG-induced CM mice. AMPK may provide new insights into interventions for energy metabolism disorders and neurogenic inflammation in migraine.


Assuntos
Transtornos de Enxaqueca , Nitroglicerina , Camundongos , Animais , Nitroglicerina/efeitos adversos , Microglia/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , NF-kappa B/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Sensibilização do Sistema Nervoso Central/fisiologia , Inflamação Neurogênica/metabolismo , Dor/metabolismo , Transtornos de Enxaqueca/induzido quimicamente , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/metabolismo
6.
Rheumatol Int ; 44(5): 795-804, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38492047

RESUMO

The aim of this study was to evaluate the effectiveness of balance exercises on functional status, pain, balance, and central sensitization in patients with knee osteoarthritis (OA). Patients diagnosed with bilateral Kellgren-Lawrence grade ≥ 2 primary knee OA and associated central sensitization were included in the study. Patients were randomized into two groups. Both groups were provided with verbal and written information on knee OA. In addition, the intervention group received a supervised balance exercise program for 6 weeks, 3 days a week on alternating days. The outcome measures were the changes in the Central Sensitization Inventory (CSI), Visual Analog Scale (VAS) pain, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Berg Balance Scale, and Y Balance Test. Evaluations were performed at baseline, immediately after treatment (6th week) and at 12th week. The study included 40 patients, 20 patients in each group. At the end of the treatment period (6th week), the improvement in CSI score, WOMAC pain, WOMAC physical function, WOMAC total score, Y Balance Test scores, and VAS pain during activity was significantly greater in the intervention group than that in the control group (p < 0.001). Regarding the changes from baseline to the 12th week, the intervention group experienced greater improvement in most of the outcome measures. Yet, the change in WOMAC pain score, Berg Balance Scale score, and VAS pain at rest was similar between the study groups (p = 0.05, p = 0.257, and p = 0.385, respectively). A two-model multiple linear regression analysis revealed that the changes in VAS pain (during activity) after the treatment and at follow-up [(p = 0.004, adjusted R2: 0.346) and (p = 0.002, adjusted R2: 0.391), respectively], as well as changes in WOMAC pain from baseline to follow-up (p = 0.020, ΔR2 = 0.245) significantly affected central sensitization. However, changes in Y Balance Test and WOMAC total scores did not appear to have a significant impact on the improvement in central sensitization (p > 0.05). Balance exercises may provide improvement in central sensitization, functional status, and dynamic balance among patients with knee OA. The improvement in central sensitization depends mostly on the pain relief effect of balance exercises.


Assuntos
Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/terapia , Sensibilização do Sistema Nervoso Central , Resultado do Tratamento , Terapia por Exercício , Dor
8.
Physiol Behav ; 277: 114503, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38403260

RESUMO

PURPOSE: As a frequently occurring complication resulting from brachial plexus avulsion (BPA), neuropathic pain significantly impacts the quality of life of patients and places a substantial burden on their families. Recent reports have suggested that the 5-HT3a receptor may play a role in the development and regulation of neuropathic pain. The current study aimed to explore the involvement of the 5-HT3a receptor in neuropathic pain resulting from BPA in rats. METHODS: A rat model of neuropathic pain was induced through brachial plexus avulsion (BPA). The pain thresholds of the rats were measured after BPA. The spinal dorsal horn (SDH) of rats was collected at day 14 after surgery, and the expression and distribution of the 5-HT3a receptor were analyzed using immunohistochemistry and western blotting. The expression levels of various factors related to central sensitization were measured by western blot, including c-Fos, GFAP, IBA-1, IL-1ß and TNF-α. The effects of 5-HT3a receptor antagonists on hyperalgesia were assessed through behavioral tests after intrathecal administration of ondansetron. Additionally, at 120 min postinjection, the SDH of rats was acquired, and the change of expression levels of protiens related to central sensitization were measured by western blot. RESULTS: BPA induced mechanical and cold hypersensitivity in rats. The 5-HT3a receptor was increased and mainly distributed on neurons and microglia in the SDH after BPA, and the level of central sensitization and expression of inflammatory factors, such as c-Fos, GFAP, IBA-1, IL-1ß and TNF-α, were also increased markedly. Ondansetron, which is a selective 5-HT3a receptor antagonist, reversed the behavioral changes caused by BPA. The antagonist also decreased the expression of central sensitization markers and inflammatory factors. CONCLUSION: The results suggested that the 5-HT3a receptor is involved in neuropathic pain by regulating central nervous system sensitization in a rat brachial plexus avulsion model. Targeting the 5-HT3a receptor may be a promising approach for treating neuropathic pain after brachial plexus avulsion.


Assuntos
Plexo Braquial , Neuralgia , Humanos , Ratos , Animais , Sensibilização do Sistema Nervoso Central , Fator de Necrose Tumoral alfa/metabolismo , Ondansetron/farmacologia , Qualidade de Vida , Plexo Braquial/metabolismo , Neuralgia/metabolismo , Hiperalgesia
9.
Int J Rheum Dis ; 27(2): e15066, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38334253

RESUMO

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.


Assuntos
Fibromialgia , Neuralgia , Pseudotumor Cerebral , Humanos , Feminino , Pseudotumor Cerebral/diagnóstico por imagem , Pseudotumor Cerebral/epidemiologia , Fibromialgia/diagnóstico por imagem , Fibromialgia/epidemiologia , Qualidade de Vida , Sensibilização do Sistema Nervoso Central , Neuralgia/diagnóstico por imagem , Neuralgia/epidemiologia , Fadiga , Cefaleia
10.
Sci Rep ; 14(1): 4873, 2024 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418550

RESUMO

Central sensitization-related symptoms (CSS) are associated with the severity and progression of pain. The relationship between the severity of pain/CSS and clinical progresses remains unclear. This multicenter, collaborative, longitudinal study aimed to characterize the clinical outcomes of patients with musculoskeletal pain by classifying subgroups based on the severity of pain/CSS and examining changes in subgroups over time. We measured the pain intensity, CSS, catastrophic thinking, and body perception disturbance in 435 patients with musculoskeletal pain. Reevaluation of patients after one month included 166 patients for pain intensity outcome and 110 for both pain intensity and CSS outcome analysis. We classified the patients into four groups (mild pain/CSS, severe pain/mild CSS, severe pain/CSS, and mild pain/severe CSS groups) and performed multiple comparison analyses to reveal the differences between the CSS severity groups. Additionally, we performed the adjusted residual chi-square to identify the number of patients with pain improvement, group transition, changing pain, and CSS pattern groups at baseline. The most characteristic result was that the mild and severe CSS groups showed worsening pain. Moreover, many of the group transitions were to the same group, with a few transitioning to a group with mild pain/CSS. Our findings suggest that the severity and improvement of CSS influence pain prognosis.


Assuntos
Sensibilização do Sistema Nervoso Central , Dor Musculoesquelética , Humanos , Medição da Dor , Estudos Longitudinais , Progressão da Doença
11.
J Anesth ; 38(2): 198-205, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38265695

RESUMO

PURPOSE: This study aimed to investigate whether smoking is an independent risk factor for central sensitization syndrome (CSS) in individuals with pain as measured by the Central Sensitization Inventory (CSI). METHODS: In 2020, we conducted an Internet survey targeting 2000 ordinary residents of Japan (aged 20-69 years) who had pain symptoms from October to November 2020. A multiple regression analysis was performed on the association between smoking status (nonsmokers and current smokers; Brinkman index) and CSI values. Moreover, compared to nonsmokers, the relative risk (RR) of the CSI cut-off score of 40 points or higher among current smokers was calculated using a modified Poisson regression model. Covariates included age, sex, body mass index, marital status, equivalized income, exercise habits, history of hypertension, history of hyperlipidemia, history of diabetes, pain chronicity, and Pain Catastrophizing Scale score. RESULTS: This study analyzed 1,822 individuals (1,041 men and 781 women). Among those experiencing pain, current smoking was associated with the increase in CSI values (ß = 0.07). The Brinkman index was also significantly associated with the increase in CSI values (ß = 0.06). Current smoking also increased the risk of being over the CSI cut-off score, with a relative risk (RR) of 1.29 (95% confidence intervals, 1.04-1.60). Younger age, being women, experiencing chronic pain, and higher pain catastrophizing thinking were also significantly associated with increased CSS severity, independent of smoking status. CONCLUSION: Smoking is an independent risk factor for CSS. This indicates that smoking may be an important factor in the management of central pain disorders.


Assuntos
Dor Crônica , Neuralgia , Masculino , Humanos , Feminino , Sensibilização do Sistema Nervoso Central , Estudos Transversais , Dor Crônica/diagnóstico , Inquéritos e Questionários , Fumar/efeitos adversos , Fumar/epidemiologia
12.
Pain Manag Nurs ; 25(2): e126-e131, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38272764

RESUMO

BACKGROUND: It is unknown if central sensitization (CS)-related symptoms have an intermediate role that might explain how disability develops from pain after cervical spinal surgery. AIMS: The study aim was to investigate the role of CS-related symptoms in the relationship between pain and disability reported after cervical spinal surgery. DESIGN: Cross-sectional study. SETTINGS: Tertiary care spinal surgery center. PARTICIPANTS/SUBJECTS: The participants included individuals with a cervical degenerative condition who had undergone surgery. METHODS: The following patient-reported outcome measures were evaluated: (1) Numerical Rating Scale; (2) Neck Disability Index; and (3) Short Form of the Central Sensitization Inventory. A hypothesized model containing the CS-related symptoms and the relationships between pain and disability was constructed and tested by structural equation modeling. RESULTS: Questionnaires were mailed to 280 individuals, and responses were obtained from 145 participants. Of these respondents, 99 (68.3%) were males and 46 (31.7%) were females, with a mean age of 64.4 ± 12.3 years. The latent variable for pain, represented by the neck (coefficient: 0.856, p < .001) and upper limb pain (0.568, p < .001), influenced CS-related symptoms (coefficient: 0.504, p < .001). Pain directly affected disability (coefficient: 0.497, p < .001) and indirectly through CS-related symptoms. Bootstrap analysis confirmed this indirect effect (point estimate: 2.85, 95% confidence interval: 1.04 to 6.30, p = .04). CONCLUSIONS: The results revealed that neck and upper limb pain affected disabilities both directly and through CS-related symptoms. Future research should focus on the efficacy of biopsychosocial approaches for patients after cervical spine surgery with a high risk of disability due to CS-related symptoms.


Assuntos
Sensibilização do Sistema Nervoso Central , Dor , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Medição da Dor/métodos , Vértebras Cervicais/cirurgia , Avaliação da Deficiência
13.
Neurourol Urodyn ; 43(3): 620-627, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38221860

RESUMO

AIM: To examine central sensitization (CS), and to investigate the relationship between CS, and urinary symptom severity, and quality of life (QoL) in women with overactive bladder (OAB). MATERIALS AND METHODS: A total of 144 women with OAB included the study. CS with the Central Sensitization Inventory (CSI), urinary symptom with the Overactive Bladder Questionnaire-Version 8 (OAB-V8), bladder diary and Patients' Perception of Intensity of Urgency Scale (PPIUS) and QoL with the King's Health Questionnaire (KHQ) were assessed. RESULTS: It was found that 47.9% (n = 69) of women with OAB had CS. It was observed that the CSI score was related to the OAB-V8 score (ρ = 0.327; p < 0.001) and the average number of voids/day (ρ = 0.291; p < 0.001). Additionally, urgency severity was higher in women with OAB with CS than in women with OAB without CS (p = 0.006). There was a relationship between the CSI score and KHQ-incontinence impact (ρ = 0.250; p = 0.012), KHQ-personal relationship (ρ = 0.253; p = 0.002), KHQ-sleep/energy (ρ = 0.180; p = 0.031), KHQ-emotional state (ρ = 0.310; p < 0.001) and KHQ-severity measurement scores (ρ = 0.391; p < 0.001). CONCLUSION: In this study, it was observed that the majority of women with OAB had CS. It was found that more severe symptoms of CS were associated with worse urinary symptom severity and QoL in these patients. It may be beneficial to evaluate CS in the management of OAB and to consider CS when determining treatment strategies.


Assuntos
Bexiga Urinária Hiperativa , Incontinência Urinária , Humanos , Feminino , Bexiga Urinária Hiperativa/diagnóstico , Qualidade de Vida , Sensibilização do Sistema Nervoso Central , Incontinência Urinária/complicações , Inquéritos e Questionários , Resultado do Tratamento
14.
Exp Aging Res ; 50(2): 155-170, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38192192

RESUMO

OBJECTIVE: To investigate whether central sensitization (CS) in elderly patients was a predictive risk factor for postoperative neurocognitive dysfunction (PNCD). METHODS: One hundred and thirty-three aged patients undergoing total knee arthroplasty (TKA) who received femoral nerve block and general anesthesia were recruited in this research and prospectively assigned into two groups according to the Central Sensitization Inventory (CSI) score: group C (n = 106, CSI score less than 40) and group CS (n = 27, CSI score higher than 40). Scores of Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Confusion Assessment Method (CAM), Numerical Rating Scale (NRS) and Quality of recovery-40 (QoR-40) questionnaires were assessed. Basic information and clinical records of all participants were also collected. RESULTS: PNCD occurred in 24 (22.6%) of patients in group C and 16 (59.3%) in group CS (p < .05). Multivariate logistic regression analysis revealed that patients with CSI score ≥40 before surgery exhibited higher risk of PNCD after adjustment for other risk factors (p < .05). Compared to group C, the pre- and post-operative NRS scores, pain duration, the WOMAC score, and propofol consumptions for anesthesia induction were significantly increased in group CS (p < .05). CONCLUSION: Hospitalized elderly patients with clinical symptoms of CS scores may have increased risk of PNCD following TKA.


Assuntos
Sensibilização do Sistema Nervoso Central , Propofol , Idoso , Humanos , Estudos Prospectivos , Envelhecimento , Testes de Estado Mental e Demência
16.
J Headache Pain ; 25(1): 3, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38177990

RESUMO

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.


Assuntos
Transtornos de Enxaqueca , NF-kappa B , Animais , Camundongos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Sensibilização do Sistema Nervoso Central/fisiologia , Citocinas/metabolismo , Inflamassomos/efeitos adversos , Inflamassomos/metabolismo , Lipopolissacarídeos , Microglia/metabolismo , Transtornos de Enxaqueca/metabolismo , Doenças Neuroinflamatórias , NF-kappa B/metabolismo , Nitroglicerina/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo
17.
Biomolecules ; 14(1)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38254671

RESUMO

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.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Dor Crônica , Humanos , Sistema Nervoso Central , Sensibilização do Sistema Nervoso Central , Doenças Neuroinflamatórias
18.
Int Urogynecol J ; 35(1): 227-236, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38165443

RESUMO

INTRODUCTION AND HYPOTHESIS: Women with central sensitisation syndrome (CSS) experience poorer subjective post-operative outcomes even after successful pelvic floor reconstruction. This study tests the hypothesis that women with pelvic floor symptoms (PFS) without relevant pelvic organ prolapse (POP), are more likely to have CSS. METHODS: A questionnaire was sent to women who participated in the POP-UP study in 2017. The POP-UP study evaluated POP in 247 women 16 years after laparoscopic or vaginal hysterectomy. POP-Q data and Pelvic Floor Distress Inventory (PFDI-20) results were used and supplemented with CSS-specific questionnaires. A Central Sensitisation Inventory (CSI) score above 40 implicates CSS. Women were divided into groups based on POP beyond the hymen in relation to the PFDI-20 score. Outcomes of women with PFS and without POP (called 'group 1') were compared with the rest of the cohort (groups 2-4; women without PFS and/or with POP). RESULTS: A total of 136 women were included in the analysis. A CSI score above 40 was present in 16 out of 42 women of group 1 (37%) versus 11 out of 93 women of groups 2-4 (12%), p < 0.0001. Passive coping was more prevalent in group 1 (p = 0.039), and more deviations in somatisation, depression, anxiety and distress were found in group 1 (p values of < 0.0001, 0.018, 0.003 and 0.002 respectively). CONCLUSIONS: This study suggests that CSS might be more prevalent in women with PFS without relevant POP. More awareness of CSS and valid individual counselling may overcome unnecessary surgery for POP and help in setting realistic expectations.


Assuntos
Diafragma da Pelve , Prolapso de Órgão Pélvico , Feminino , Humanos , Diafragma da Pelve/cirurgia , Sensibilização do Sistema Nervoso Central , Prolapso de Órgão Pélvico/complicações , Prolapso de Órgão Pélvico/cirurgia , Prolapso de Órgão Pélvico/diagnóstico , Inquéritos e Questionários , Histerectomia Vaginal , Qualidade de Vida
19.
J Rheumatol ; 51(2): 144-149, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37967915

RESUMO

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.


Assuntos
Artrite Psoriásica , Adulto , Humanos , Artrite Psoriásica/diagnóstico , Qualidade de Vida , Sensibilização do Sistema Nervoso Central , Estudos Transversais , Índice de Gravidade de Doença
20.
J Bone Joint Surg Am ; 106(2): 102-109, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-37943951

RESUMO

UPDATE: This article was updated on November 17, 2023, because of previous errors, which were discovered after the preliminary version of the article was posted online. On page 102, the text that had read "In a post hoc analysis of the preoperative results, Group 1 showed significantly inferior WOMAC pain, function, and total scores compared with Group 4 (p < 0.05 for all). Groups 2 and 3 showed worse preoperative WOMAC pain, function, and total subscores compared with Group 4 (p < 0.05 for all). These results remained the same at 2 years after surgery." now reads "In a post hoc analysis of the preoperative results, Groups 1, 2, and 3 showed significantly inferior WOMAC pain, function, and total scores compared with Group 4 (p < 0.05 for all). At 2 years postoperatively, Group 1 showed inferior WOMAC pain, function, and total scores compared with the other groups (p < 0.05 for all). Also, Groups 2 and 3 had worse WOMAC pain, function and total scores compared with Group 4 (p < 0.05 for all)." Also, on page 106, the title of Table IV, which had previously read "Inter-Group Comparison of Preoperative Scores (Post Hoc Analysis)" now reads "Inter-Group Comparison of Postoperative Scores (Post Hoc Analysis)."


Available studies on the relationship between central sensitization and neuropathic pain, and on their association with patient-reported outcome measures (PROMs), following total knee arthroplasty (TKA) are insufficient. The purpose of the present study was to investigate this association. A total of 316 patients who underwent primary unilateral TKA for the treatment of end-stage osteoarthritis (OA) of the knee were enrolled. Central sensitization was defined as a score of ≥40 on the Central Sensitization Inventory. Neuropathic pain was defined as a score of ≥19 on the painDETECT Questionnaire (PDQ). PROMs were also evaluated on the basis of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score preoperatively and at 2 years postoperatively. The patients were divided into 4 groups: Group 1 had both central sensitization and neuropathic pain, Group 2 had central sensitization only, Group 3 had neuropathic pain only, and Group 4 had neither central sensitization nor neuropathic pain. Preoperative and postoperative PROMs were compared among the groups. All individuals who participated in the study were Asian, especially Korean. Fifty-five patients (17.4%) had both central sensitization and neuropathic pain, 68 (21.5%) had central sensitization only, 35 (11.1%) had neuropathic pain only, and 158 (50.0%) had neither condition. All WOMAC subscores showed significant differences among the 4 groups before and after surgery (p < 0.05 for all). In a post hoc analysis of the preoperative results, Groups 1, 2, and 3 showed significantly inferior WOMAC pain, function, and total scores compared with Group 4 (p < 0.05 for all). At 2 years postoperatively, Group 1 showed inferior WOMAC pain, function, and total scores compared with the other groups (p < 0.05 for all). Also, Groups 2 and 3 had worse WOMAC pain, function and total scores compared with Group 4 (p < 0.05 for all). Each condition, central sensitization and neuropathic pain, was associated with inferior PROMs following TKA. Furthermore, patients with both central sensitization and neuropathic pain showed worse PROMs compared with patients with either condition alone or without either condition. Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Artroplastia do Joelho , Neuralgia , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/efeitos adversos , Osteoartrite do Joelho/cirurgia , Sensibilização do Sistema Nervoso Central , Resultado do Tratamento , Articulação do Joelho/cirurgia
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