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1.
BMC Neurol ; 19(1): 239, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623575

RESUMO

BACKGROUND: Medication Overuse Headache (MOH) is a prevalent and disabling disorder resulting from the overuse of analgesic drugs, triptans or other acute headache medications. In previous proteomic studies, several proteins have been found at high concentrations in the urine of MOH patients and in the serum of rats with neuropathic pain. The aim of this study was to compare the serum levels of lipocalin-type Prostaglandin D2 synthase (L-PGDS), Vitamin D-binding protein (VDBP), apolipoprotein E (APOE) and apolipoprotein A1 (APOA1) in MOH patients and healthy individuals, further exploring their relationship with cutaneous pain thresholds (CPTs) in the territories innervated by the trigeminal nerve. METHODS: Sixty-nine MOH patients and 42 age- and sex-matched healthy volunteers were enrolled in the study. Von Frey-like filaments were applied to the skin territories innervated by the trigeminal nerve, to determine the CPTs. L-PGDS, VDBP, APOE and APOA1 were quantified in the serum by Enzyme-linked Immunosorbent Assay (ELISA). Clinical and laboratory data were collected. Comparisons between MOH patients and healthy individuals were performed using independent t test or χ2 test. To correlate serum proteins with CPTs, Pearson correlation coefficient or Spearman's rank correlation coefficient were used. RESULTS: CPTs were lower among MOH patients. L-PGDS, VDBP and APOE had significantly different serum concentrations between groups (p < 0.01), but no correlation was found with CPTs. APOA1 serum concentrations did not differ between patients and healthy individuals. CONCLUSIONS: L-PGDS, VDBP and APOE had abnormal serum levels in MOH patients, confirming their alteration in some conditions of chronic headache and neuropathic pain. However, they had no relationship with CPTs. The in-depth study of serum proteins represents a promising approach for a better understanding of MOH, as well as the detection of candidate biomarkers for chronic headache or the risks associated with overuse medications.


Assuntos
Biomarcadores/sangue , Transtornos da Cefaleia Secundários/sangue , Adulto , Animais , Dor Crônica/sangue , Feminino , Transtornos da Cefaleia/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Proteômica , Ratos
2.
Dokl Biochem Biophys ; 485(1): 145-149, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31201637

RESUMO

Variation of natural antibody (nAb) levels to the pain bioregulators (ß-endorphin, orphanin, serotonin, dopamine, histamine, and angiotensin) in blood serum at chronic low back pain (LBP) was studied for 21 days. We revealed gender features of immuno-profiles: more elevated nAb levels in women at 1st day and equal levels in gender groups at 21st day. In addition, nAb levels remained above normal up to day 21 in most of patients despite a threefold decrease in pain intensity, measured using a differential visual analogue scale. A significant decrease in nAb levels was found in 4-20% of patients depending on the bioregulator. These observations support the hypothesis that antibodies can be a factor in the prolongation of pain. Therefore, the analysis of the dynamics of nAbs can be recommended for patients with LBP, from which it is possible to predict the further course of the disease.


Assuntos
Autoanticorpos/imunologia , Dor Crônica/imunologia , Imunidade Humoral , Dor Lombar/imunologia , Adulto , Autoanticorpos/sangue , Dor Crônica/sangue , Humanos , Dor Lombar/sangue , Masculino , Pessoa de Meia-Idade
3.
Neurosci Lett ; 706: 105-109, 2019 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-31100426

RESUMO

Central sensitivity syndrome (CSS) consists of adaptive pathophysiological changes associated with neuroplasticity in some chronic pain disorders. It could be grouped in two main conceptual conditions: one includes those chronic pain patients without overt structural pathology such as fibromyalgia, and the other subgroup includes conditions with recognizable structural abnormalities, both somatic (osteoarthritis) and visceral (endometriosis). In order to understand the role of neuromodulators in CCS we aim to determine whether brain-derived neurotrophic factor (BDNF) and S100B are associated to specific chronic pain disorders. Serum BDNF and S100B were measured in chronic pain women with different diagnosis: 88 with osteoarthritis, 36 with endometriosis, 117 with fibromyalgia, 33 with chronic tension type headache and in 41 healthy controls. ANCOVA analysis followed by heteroscedasticity-consistent covariance matrix was performed to evaluate BDNF and S100B levels, adjusted for depression severity, pain levels and use of analgesics according different pathologies. Serum BDNF concentrations were higher and not different in patients with fibromyalgia and headache, the CSS group without structural pathology. In contrast, the concentrations of S100B were higher in patients with osteoarthritis and endometriosis, in comparison to controls, fibromyalgia and tensional headache patients. This study supports the hypothesis that BDNF and S100B neuromodulators present different serum levels according to the background disease associated to the chronic pain. These have the potential to be studied as markers of active disease or treatment evolution.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Dor Crônica/sangue , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Adulto , Biomarcadores/sangue , Estudos Transversais , Endometriose/sangue , Feminino , Fibromialgia/sangue , Humanos , Osteoartrite/sangue , Cefaleia do Tipo Tensional/sangue
4.
Indian J Med Res ; 149(1): 47-50, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31115374

RESUMO

Background & objectives: : Fibromyalgia syndrome (FMS) is one of the most common chronic pain conditions of unknown aetiology. Mitochondrial dysfunction has been reported in FMS with some studies reporting the presence of mitochondrial mutation namely A3243G, which also causes mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. This pilot study was conducted to assess this mutation and also detect large deletions in mitochondrial DNA (mtDNA) in patients with FMS. Methods: : Thirty female patients with FMS participated and 30 matched controls were included. Genomic DNA was subjected to polymerase chain reaction (PCR) amplification using specific primers followed by restriction digestion with Apa I enzyme to detect the specific A3243G mtDNA mutation. Long-range PCR was done in two sets to detect the large deletions in the mtDNA. Biochemical parameters including thyroid-stimulating hormone and vitamin D levels were also looked at. Results: : None of the patients were found to carry the common mutation or large deletions. Low vitamin D level was a common finding. Hypothyroidism was found in a few patients. Interpretation & conclusions: : Although the common mutation or large mtDNA deletions were not detected in blood mtDNA in the FMS patients, mutations in the muscle and sequence variation in mtDNA remained a possibility. Future studies in both blood and muscle tissue including mtDNA sequencing are warranted in such patients to determine if a subset of FMS patients have mitochondrial myopathy.


Assuntos
Dor Crônica/genética , DNA Mitocondrial/genética , Fibromialgia/genética , Mitocôndrias/genética , Adulto , Idoso , Dor Crônica/sangue , Dor Crônica/fisiopatologia , DNA Mitocondrial/sangue , Feminino , Fibromialgia/sangue , Fibromialgia/fisiopatologia , Humanos , Pessoa de Meia-Idade , Mitocôndrias/patologia , Mutação/genética , Fenótipo , Projetos Piloto , Deleção de Sequência/genética , Vitamina D/sangue , Vitamina D/genética
5.
Ren Fail ; 41(1): 257-266, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31014149

RESUMO

BACKGROUND AND OBJECTIVES: Chronic musculoskeletal (MS) pain is common in chronic kidney disease (CKD) patients. The association of chronic MS pain and CKD progression has not yet been established. METHOD: We conducted a prospective cohort study to evaluate the association of chronic MS pain and CKD progression of pre-dialysis CKD patients. RESULT: A total of 53.2% of pre-dialysis CKD patients had chronic MS pain. Patients classified as progression and non-progression had a similar prevalence of chronic MS pain at baseline, and similar baseline use of NSAIDs and Chinese herbal medicines. Univariate Cox analysis indicated that chronic MS pain and baseline NSAID or Chinese herbal medicine use were not significantly associated with progression of CKD. But multivariate Cox regression found chronic MS pain was independently significantly associated with all-cause mortality (HR, 2.912, 95% CI, 1.004-8.444; p = .049). However, serum levels of hs-CRP were similar between those chronic MS pain patients and without chronic MS pain patients (4.96 ± 9.4 vs. 4.25 ± 13.3 mg/L, p = .535). CONCLUSION: The CKD patients with chronic MS pain was independently and significantly associated with all-cause mortality, but not independently and significantly associated with CKD progression and composite endpoints. The inflammatory marker-hs-CRP was similar between CKD patients with and without chronic MS pain.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Dor Crônica/epidemiologia , Dor Musculoesquelética/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Idoso , Proteína C-Reativa/análise , Dor Crônica/sangue , Dor Crônica/tratamento farmacológico , Dor Crônica/etiologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/sangue , Dor Musculoesquelética/tratamento farmacológico , Dor Musculoesquelética/etiologia , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia , Medição de Risco , Índice de Gravidade de Doença
6.
Kaohsiung J Med Sci ; 35(3): 139-145, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30887716

RESUMO

Accumulating evidences indicates that chronic neuropathic pain is a kind of neuro-immune disorder with enhanced activation of the immune system. Although the prevalence is very high, neuropathic pain remains extremely difficult to cure. miRNAs are a group of short nonprotein coding RNAs, regulating target genes expression via targeting 3'-untranslated region. More and more research indicates that altered miRNAs expression profile relates to the pathogenesis of neuropathic pain. In this study, we firstly detected the expression of six candidate miRNAs in the plasma samples from 23 patients with neuropathic pain and 10 healthy controls. Subsequently, the level of miR-132 and miR-101 was detected in the sural nerve biopsies. We found miR-101 level was significantly repressed in both the plasma samples and sural nerve biopsies from neuropathic pain patients. Predicted by bioinformatics tools and confirmed by dual luciferase assay and immunoblotting, we identified that KPNB1 is a direct target of miR-101. The negative correlation between miR-101 and KPNB1 was also confirmed in the sural nerve biopsies, and miR-101 reduction relates to the activation of NF-κB signaling in vivo and in vitro which contributes to the pathogenesis of neuropathic pain.


Assuntos
Dor Crônica/genética , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Neuralgia/genética , Transdução de Sinais , beta Carioferinas/metabolismo , Regiões 3' não Traduzidas/genética , Adulto , Idoso , Sequência de Bases , Estudos de Casos e Controles , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Dor Crônica/sangue , Feminino , Regulação da Expressão Gênica , Células HEK293 , Humanos , Interleucina-1beta/metabolismo , Masculino , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Neuralgia/sangue , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , beta Carioferinas/genética
7.
J Steroid Biochem Mol Biol ; 188: 17-22, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30508645

RESUMO

Chronic pain is a major contributor to the global burden of disability. Prior studies on the association between serum 25-hydroxyvitamin D (25(OH)D) levels and chronic pain have yielded mixed results. The Vitamin D Assessment study, a large randomized controlled trial from New Zealand, offered the opportunity to examine this association in data collected at baseline in all participants, and among those with arthritis or depression. A total of 5110 participants aged 50-84 years were recruited from community general practices. Chronic pain (lasting ≥6 months) and other baseline characteristics were collected at baseline interview. Serum 25(OH)D concentration was measured by liquid chromatography-tandem mass spectrometry. Associations between 25(OH)D levels and chronic pain were explored using multivariable log-binomial regression to estimate relative risks (RRs). Out of 5049 participants with complete data, 871 (17%) reported having this clinical outcome, and 1254 (25%) had a 25(OH)D concentration <50 nmol/L. There was no significant association between 25(OH)D and chronic pain, with vitamin D status categorized in four groups: <25.0, 25.0-49.9, 50.0-74.9, and ≥75.0 nmol/L (the highest group as reference). The unadjusted RRs were 1.09, 1.10, and 1.08, respectively (Ptrend = 0.24). Adjustment for demographics, lifestyle, BMI, medical history, prescription of analgesics and vitamin D supplements did not change this finding. Similar non-significant results were observed in participants with arthritis (n = 1732) or depression (n = 528). In this multi-ethnic, community-selected sample of older adults in New Zealand, serum 25(OH)D levels were not associated with chronic pain. These results do not support a role for low vitamin D status in the prevalence of chronic pain in older adults.


Assuntos
Dor Crônica/sangue , Vitamina D/análogos & derivados , Vitaminas/sangue , Idoso , Idoso de 80 Anos ou mais , Dor Crônica/etiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Autorrelato , Vitamina D/sangue
8.
Pain Pract ; 19(4): 370-381, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30457698

RESUMO

BACKGROUND: The role of contextual factors like pre-existing treatment expectations has been established. However, the effect of verbally delivered treatment expectations in patient-therapist communication has not been considered, nor has the role of cortisol changes within the placebo/nocebo response in people with chronic neck pain. OBJECTIVE: To examine the effect of verbally delivered treatment expectations on clinical outcomes in physical therapy practice and to determine if changes in cortisol levels are associated with changes in neck pain and disability. METHODS: Eighty-three patients with chronic neck pain were randomly allocated to 3 different verbally delivered expectations (positive, negative, neutral) during physical therapy interventions. MAIN OUTCOME MEASURES: salivary cortisol, pain and disability, and cervical range of motion. RESULTS: Pain significantly improved in the positive (P < 0.001) and neutral (P < 0.001) expectations groups. For salivary cortisol levels, a significant increase was observed in response to treatment in the neutral (P = 0.045) and negative (P < 0.001) expectations groups. No significant correlations were found between changes in salivary cortisol levels and the change in pain in the neutral and negative expectations groups. CONCLUSIONS: Physical therapists treating people with chronic neck pain should be attentive when communicating the expected treatment effects to their patients. Whereas verbally delivered positive or neutral expectations may be beneficial for pain-related measures, giving negative expectations may result in a lack of a treatment response on pain. Cortisol levels increased in response to verbally delivered neutral and negative expectations, in the absence of a nocebo effect. This questions the presumed role of cortisol in the nocebo effect.


Assuntos
Hidrocortisona/sangue , Motivação , Cervicalgia/sangue , Cervicalgia/psicologia , Cervicalgia/reabilitação , Adulto , Dor Crônica/sangue , Dor Crônica/psicologia , Dor Crônica/reabilitação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Efeito Nocebo , Modalidades de Fisioterapia
9.
Eur J Pain ; 23(2): 327-340, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30125426

RESUMO

BACKGROUND: Monoaminergic pathways are involved in the process of pain inhibition and facilitation. The objective of this study was to investigate the role of blood monoamines as biomarkers of conditioned pain modulation (CPM) efficacy. METHODS: One hundred and five paediatric patients with chronic back pain were enrolled in this observational study. The protocol involved dosage of plasma monoamines (dopamine, DOPA; serotonin, 5-HT; epinephrine, Epi; norepinephrine, NE; metanephrine, ME; and normetanephrine, NME) and clinical assessment (CPM, functional disability, pain, sleep quality, anxiety and depression). RESULTS: 5-HT and DOPA were positively correlated among each other and were both negatively correlated with Epi, ME, NE and NME. CPM presented a positive correlation with DOPA and 5-HT. On the other hand, Epi, ME, NE and NME correlated negatively with CPM. Different correlation coefficients were observed between genders, with stronger coefficients being observed in the male subpopulation. Stepwise regression controlling for age and gender indicated that ME (B = -0.987, SE(B) = 0.299, p = 0.002) was the only significant predictor for CPM efficacy. Higher blood ME was associated with poorer CPM efficacy. ME explained 53% of variation of CPM in males (R2  = 0.536, p < 0.0001) and 7% in females (R2  = 0.074, p = 0.014). In males, blood ME >15 pg/ml predicted inefficient CPM with 88.9% sensitivity and 83.3% specificity. CONCLUSIONS: Our findings suggest that ME can be a potential biomarker for CPM efficacy in paediatrics. Future studies are needed to assess the efficacy of tailored treatments for pain according to blood ME. SIGNIFICANCE: We were able to demonstrate an association between CPM and circulating monoamines. In the clinical setting, sampling ME could provide the clinician an idea of the individual's pain modulation potential. This may be particularly important for children with cognitive impairment, for whose CPM paradigm cannot be used.


Assuntos
Dor nas Costas/sangue , Monoaminas Biogênicas/sangue , Dor Crônica/sangue , Adolescente , Dor nas Costas/diagnóstico , Dor nas Costas/psicologia , Biomarcadores/sangue , Criança , Pré-Escolar , Dor Crônica/diagnóstico , Dor Crônica/psicologia , Dopamina , Feminino , Humanos , Lactente , Masculino , Medição da Dor , Serotonina
10.
Pain ; 160(3): 676-687, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30562268

RESUMO

We sought to replicate previous findings that low endogenous opioid (EO) function predicts greater morphine analgesia and extended these findings by examining whether circulating endocannabinoids and related lipids moderate EO-related predictive effects. Individuals with chronic low-back pain (n = 46) provided blood samples for endocannabinoid analyses, then underwent separate identical laboratory sessions under 3 drug conditions: saline placebo, intravenous (i.v.) naloxone (opioid antagonist; 12-mg total), and i.v. morphine (0.09-mg/kg total). During each session, participants rated low-back pain intensity, evoked heat pain intensity, and nonpain subjective effects 4 times in sequence after incremental drug dosing. Mean morphine effects (morphine-placebo difference) and opioid blockade effects (naloxone-placebo difference; to index EO function) for each primary outcome (low-back pain intensity, evoked heat pain intensity, and nonpain subjective effects) were derived by averaging across the 4 incremental doses. The association between EO function and morphine-induced back pain relief was significantly moderated by endocannabinoids [2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)]. Lower EO function predicted greater morphine analgesia only for those with relatively lower endocannabinoids. Endocannabinoids also significantly moderated EO effects on morphine-related changes in visual analog scale-evoked pain intensity (2-AG), drug liking (AEA and 2-AG), and desire to take again (AEA and 2-AG). In the absence of significant interactions, lower EO function predicted significantly greater morphine analgesia (as in past work) and euphoria. Results indicate that EO effects on analgesic and subjective responses to opioid medications are greatest when endocannabinoid levels are low. These findings may help guide development of mechanism-based predictors for personalized pain medicine algorithms.


Assuntos
Analgésicos Opioides/uso terapêutico , Endocanabinoides/sangue , Dor Lombar/sangue , Dor Lombar/tratamento farmacológico , Morfina/uso terapêutico , Adulto , Dor Crônica/sangue , Dor Crônica/tratamento farmacológico , Dor Crônica/reabilitação , Método Duplo-Cego , Exercício/fisiologia , Feminino , Humanos , Dor Lombar/reabilitação , Masculino , Pessoa de Meia-Idade , Naloxona/uso terapêutico , Peptídeos Opioides/sangue , Medição da Dor , Análise de Regressão , Inquéritos e Questionários , Resultado do Tratamento
11.
Eur J Endocrinol ; 179(6): 353-362, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30324794

RESUMO

Objective To evaluate pituitary function, sexual function and quality of life (QoL) in patients on oral or transdermal opioids. Design and methods Cross-sectional study comparing pituitary function, QoL and sexual function in people on long-term opioid therapy (n = 40) vs an age- and sex-matched control group (n = 25). Baseline pituitary function was assessed on blood samples collected prior to 0900 h. Further testing with corticotropin (250 µg IV) and metyrapone (30 mg/kg) stimulation tests was undertaken on participants with serum cortisol <250 nmol/L. Validated questionnaires completed to assess QoL, fatigue and sexual function. Results Secondary adrenal insufficiency (SAI) was identified on the basis of a failed stimulation test in 22.5% of opioid users vs no controls (P = 0.01). Opioid users with SAI had a higher median morphine-equivalent daily dose (MEDD), P = 0.037 - 50% with MEDD >200 mg and 0% with MEDD <60 mg had SAI. Among male participants, testosterone was inversely associated with BMI (P = 0.001) but not opioid use. A non-significant trend to low testosterone <8 nmol/L in male opioid users (11/24 opioid users vs 2/14 control, P = 0.08) suggests a small subgroup with opioid-induced androgen deficiency. Opioid users had greater fatigue, reduced quality of life in all subsections of the SF-36 and impaired sexual function in both males and females (all scores P < 0.001 compared to controls). Conclusion Long-term opioid therapy was associated with dose-related SAI in over 20% of chronic pain patients and is associated with poor quality of life, fatigue and sexual dysfunction. Obesity confounds the interpretation of opioid-induced male androgen deficiency.


Assuntos
Insuficiência Adrenal/induzido quimicamente , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Dor Crônica/tratamento farmacológico , Hipófise/efeitos dos fármacos , Administração Cutânea , Administração Oral , Insuficiência Adrenal/sangue , Insuficiência Adrenal/diagnóstico , Adulto , Idoso , Dor Crônica/sangue , Dor Crônica/diagnóstico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipófise/metabolismo , Hormônios Hipofisários/sangue , Qualidade de Vida , Disfunções Sexuais Fisiológicas/sangue , Disfunções Sexuais Fisiológicas/induzido quimicamente , Disfunções Sexuais Fisiológicas/diagnóstico , Adulto Jovem
12.
Scand J Pain ; 18(2): 187-194, 2018 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-29794301

RESUMO

BACKGROUND AND AIMS: Chronic widespread pain (CWP) is associated with poor quality of sleep, but the detailed underlying mechanisms are still not fully understood. In this study we investigated the influence of CWP on morning cortisol and fasting glucose concentrations as well as sleep disordered breathing. METHODS: In this case-control study, subjects with CWP (n=31) and a control group without CWP (n=23) were randomly selected from a population-based cohort of women. Current pain intensity, sleep quality, excessive daytime sleepiness [Epworth sleepiness scale (ESS)], psychiatric comorbidity and occurrence of restless legs syndrome (RLS) were assessed. Overnight polygraphy was applied to quantify sleep apnoea, airflow limitation and attenuations of finger pulse wave amplitude (>50%) as a surrogate marker for increased skin sympathetic activity. Morning cortisol and fasting glucose concentrations were determined. Generalised linear models were used for multivariate analyses. RESULTS: CWP was associated with higher cortisol (464±141 vs. 366±111 nmol/L, p=0.011) and fasting glucose (6.0±0.8 vs. 5.4±0.7 mmol/L, p=0.007) compared with controls. The significance remained after adjustment for age, body mass index, RLS and anxiety status (ß=122±47 nmol/L and 0.89±0.28 mmol/L, p=0.009 and 0.001, respectively). The duration of flow limitation in sleep was longer (35±22 vs. 21±34 min, p=0.022), and pulse wave attenuation was more frequent (11±8 vs. 6±2 events/h, p=0.048) in CWP subjects compared with controls. RLS was associated with higher ESS independent of CWP (ß=3.1±1.3, p=0.018). CONCLUSIONS: Elevated morning cortisol, impaired fasting glucose concentration and increased skin sympathetic activity during sleep suggested an activated adrenal medullary system in subjects with CWP, which was not influenced by comorbid RLS. IMPLICATIONS: CWP is associated with activated stress markers that may deteriorate sleep.


Assuntos
Glicemia , Dor Crônica/sangue , Hidrocortisona/sangue , Síndrome das Pernas Inquietas/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Dor Crônica/epidemiologia , Estudos de Coortes , Comorbidade , Jejum , Feminino , Humanos , Transtornos Mentais/sangue , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Fotoperíodo , Análise de Onda de Pulso , Síndrome das Pernas Inquietas/epidemiologia , Sono , Síndromes da Apneia do Sono/sangue , Síndromes da Apneia do Sono/epidemiologia , Sistema Nervoso Simpático/fisiopatologia , Adulto Jovem
13.
Public Health Nutr ; 21(11): 2022-2037, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29559013

RESUMO

OBJECTIVE: Pain-related conditions, such as chronic widespread pain and fibromyalgia, are major burdens for individuals and the health system. Evidence from previous research on the association between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and pain is conflicting. Thus, we aimed to determine if there is an association between mean 25(OH)D concentration (primary aim), or proportion of hypovitaminosis D (secondary aim), and pain conditions in observational studies. DESIGN: Published observational research on 25(OH)D concentration and pain-related conditions was systematically searched for in electronic sources (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) and a random-effects meta-analysis was conducted on included studies. RESULTS: Eighty-one observational studies with a total of 50 834 participants were identified. Compared with controls, mean 25(OH)D concentration was significantly lower in patients with arthritis (mean difference (MD): -12·34 nmol/l; P<0·001), muscle pain (MD: -8·97 nmol/l; P=0·003) and chronic widespread pain (MD: -7·77 nmol/l; P<0·001), but not in patients with headache or migraine (MD: -2·53 nmol/l; P=0·06). The odds of vitamin D deficiency was increased for arthritis, muscle pain and chronic widespread pain, but not for headache or migraine, compared with controls. Sensitivity analyses revealed similar results. CONCLUSIONS: A significantly lower 25(OH)D concentration was observed in patients with arthritis, muscle pain and chronic widespread pain, compared with those without. These results suggest that low 25(OH)D concentrations may be associated with pain conditions.


Assuntos
Artrite/sangue , Dor Crônica/sangue , Mialgia/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adulto , Artrite/complicações , Dor Crônica/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mialgia/complicações , Estudos Observacionais como Assunto , Vitamina D/sangue , Deficiência de Vitamina D/complicações
14.
Pain Med ; 19(5): 1033-1043, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29016958

RESUMO

Background and Objectives: Multiple processes have been identified as potential contributors to chronic pain, with increasing evidence illustrating an association with aberrant levels of neuroimmune mediators. The primary objectives of the present study were to examine central nervous system cytokines, chemokines, and growth factors present in a chronic pain population and to explore patterns of the same mediator molecules over time. Secondary objectives explored the relationship of central and peripheral neuroimmune mediators while examining the levels of anxiety, depression, sleep quality, and perception of pain associated with the chronic pain patient experience. Methods: Cerebrospinal fluid (CSF) from a population of majority postlaminectomy syndrome patients (N = 8) was compared with control CSF samples (N = 30) to assess for significant differences in 10 cytokines, chemokines, and growth factors. The patient population was then followed over time, analyzing CSF, plasma, and psychobehavioral measures. Results: The present observational study is the first to demonstrate increased mean CSF levels of interleukin-8 (IL-8; P < 0.001) in a small population of majority postlaminectomy syndrome patients, as compared with a control population. Over time in pain patients, CSF levels of IL-8 increased significantly (P < 0.001). Conclusions: These data indicate that IL-8 should be further investigated and psychobehavioral components considered in the overall chronic pain paradigm. Future studies examining the interactions between these factors and IL-8 may identify novel targets for treatment of persistent pain states.


Assuntos
Dor Crônica/sangue , Interleucina-8/sangue , Laminectomia/efeitos adversos , Complicações Pós-Operatórias/sangue , Adulto , Idoso , Quimiocinas/sangue , Citocinas/sangue , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Sistema Nervoso/fisiopatologia
15.
Int Urol Nephrol ; 50(3): 395-399, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29235061

RESUMO

PURPOSE: Immune mechanisms have been hypothesized to contribute to the development of CP/CPPS. In this study, we investigated the differential expression of immune factors between patients with CP/CPPS and healthy volunteers. METHODS: This study was registered in Australian New Zealand Clinical Trials Registry. Healthy volunteers and patients with CP/CPPS were enrolled in this study. The inclusion criteria for patients were below: (1) aged 18-45 years old; (2) prostatitis-related syndrome longer than 3 months; (3) normal routine urine culture and negative bacterial culture in prostatic fluid. Patients were further classified into two groups: types IIIA and IIIB CP/CPPS according to the results of EPS routine test. Serum immune markers include IgA, IgM, IgG, CD4+ and CD8+. RESULTS: There are total 23 CP/CPPS patients, including 12 type IIIB and 11 type IIIA. Relatively, there are 26 healthy volunteers. The serum levels of IgG were higher in CP/CPPS patients compared to healthy volunteers (1141.2 ± 204.3 vs 1031.9 ± 173.7 mg/L, p = 0.045), while the serum levels of CD8+ were lower in CP/CPPS patients compared to healthy volunteers (492.8 ± 185.6 vs 640.0 ± 246.8 cells/µL, p = 0.021). Furthermore, serum levels of IgG were higher in patients with IIIA CP/CPPS compared to those with IIIB (1244.3 ± 151.6 vs 1054.3 ± 209.3 mg/L, p = 0.023). CONCLUSIONS: Differential levels of IgG and CD8+ between CPPS patients and healthy volunteers suggest a contributing role of immune mechanisms to the development of CP/CPPS; and IgG may play an important role in inflammatory CPPS. Clinical Study registration number ACTRN12613000792729.


Assuntos
Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos , Dor Crônica/sangue , Imunoglobulinas/sangue , Dor Pélvica/sangue , Prostatite/sangue , Adulto , Estudos de Casos e Controles , Doença Crônica , Dor Crônica/classificação , Voluntários Saudáveis , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Dor Pélvica/classificação , Prostatite/classificação , Síndrome , Adulto Jovem
16.
Biochim Biophys Acta Mol Basis Dis ; 1864(2): 601-606, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29197660

RESUMO

BACKGROUND: Fatigue is a sensation of unbearable tiredness that frequently accompanies chronic widespread musculoskeletal pain (CWP) and inflammatory joint disease. Its mechanisms are poorly understood and there is a lack of effective biomarkers for diagnosis and onset prediction. We studied the circulating metabolome in a population sample characterised for CWP to identify biomarkers showing specificity for fatigue. MATERIAL AND METHODS: Untargeted metabolomic profiling was conducted on fasting plasma and serum samples of 1106 females with and without CWP from the TwinsUK cohort. Linear mixed-effects models accounting for covariates were used to determine relationships between fatigue and metabolites. Receiver operating curve (ROC)-analysis was used to determine predictive value of metabolites for fatigue. RESULTS: While no association between fatigue and metabolites was identified in twins without CWP (n=711), in participants with CWP (n=395), levels of eicosapentaenoate (EPA) ω-3 fatty acid were significantly reduced in those with fatigue (ß=-0.452±0.116; p=1.2×10-4). A significant association between fatigue and two other metabolites also emerged when BMI was excluded from the model: 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF), and C-glycosyltryptophan (p=1.5×10-4 and p=3.1×10-4, respectively). ROC analysis has identified a combination of 15 circulating metabolites with good predictive potential for fatigue in CWP (AUC=75%; 95% CI 69-80%). CONCLUSION: The results of this agnostic metabolomics screening show that fatigue is metabolically distinct from CWP, and is associated with a decrease in circulating levels of EPA. Our panel of circulating metabolites provides the starting point for a diagnostic test for fatigue in CWP.


Assuntos
Dor Crônica/sangue , Fadiga/sangue , Metaboloma , Adulto , Idoso , Área Sob a Curva , Biomarcadores , Proteína C-Reativa/química , Dor Crônica/diagnóstico , Dor Crônica/terapia , Estudos de Coortes , Doenças em Gêmeos , Ácido Eicosapentaenoico/sangue , Fadiga/diagnóstico , Fadiga/terapia , Ácidos Graxos Ômega-3/sangue , Feminino , Furanos/sangue , Furanos/química , Glicosilação , Humanos , Inflamação , Modelos Lineares , Pessoa de Meia-Idade , Dor Musculoesquelética/patologia , Propionatos/sangue , Propionatos/química , Curva ROC , Fatores de Risco , Triptofano/química , Reino Unido
17.
Physiol Res ; 67(Suppl 4): S685-S688, 2018 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-30607975

RESUMO

Pain increased the number of free radicals in the body. Previously, we studied changes mainly in oxygen and nitroxide free radicals and described these changes relative to the lipids and saccharides. In this article we focus on changes relative to proteins. Assessment of AGE products (advanced glycation end-products) was carried out by measuring fluorescence. Patients were divided into two groups: 15 patients with acute pain and 17 patients with chronic pain. Acute pain was associated with a variety of surgical procedures and patients were examined before and after surgical procedures. The group of patients with chronic pain suffered from various types of chronic pain, but mainly back pain. In patients with acute pain, total protein (TP) decreased after surgery, as did the level of AGE and the AGE/TP ratio. Nonetheless, post-operative pain increased. In patients with chronic pain, neither total protein, AGE, or AGE/TP changed, despite significant pain relief being reported after treatment. Changes in proteins, as biochemical markers, before and after pain treatment did not show any significant changes. In patients with acute pain, the recorded changes only lasted for 3-5 days after the operation. While in chronic pain, there were no significant changes at all. The assumption that changes in proteins, as biomarkers, would have the same importance as changes in lipids and saccharides was not proven.


Assuntos
Dor Aguda/sangue , Dor Aguda/terapia , Dor Crônica/sangue , Dor Crônica/terapia , Produtos Finais de Glicação Avançada/sangue , Medição da Dor/métodos , Acetaminofen/uso terapêutico , Adulto , Analgésicos Opioides/uso terapêutico , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/sangue , Dor Pós-Operatória/terapia
18.
Patol Fiziol Eksp Ter ; 61(2): 56-60, 2017.
Artigo em Russo | MEDLINE | ID: mdl-29215841

RESUMO

Objective. To study features of histamine metabolism in patients with chronic pelvic pain associated with external genital endometriosis. Methods. For quantitative assessment of histamine level in peripheral blood was taken from 100 patients which than was centrifuged. In blood serum histamine concentration was determined by enzyme-linked immunosorbent assay method with reagents «Histamine ЕLISA¼ on the machine BAE-1000 Histamine (Labor Diagnostika Nord - LDN, Hermany). A pain syndrome was assessed by Visual Analog Scale (VAS), quality of life assessment - by Endometriosis Health Profile Questionnaire (EHR-30), level of anxiety was determined by Spielberger-Khanin questionnaire. The results. Showed statistically higher histamine level in patients with severe pain according to VAS. After assessment of results obtained from Spielberger-Khanin questionnaire 100% experimental group's women with external genital endometriosis (n = 60) were noted to be have high level of state and trait anxiety, then 40% women of control group (n = 16) have moderate level of anxiety. The incidence of depression in women with chronic pelvic pain was 58.3% (n = 35) and the main part (n = 20) were women with severe stage of pelvic pain according to VAS. Conclusions. Psycho emotional condition of women with external genital endometriosis associated pelvic pain characterized by higher depression and anxiety levels, with significant decrease quality of life. Direct relationship also was found between pain syndrome intensity and histamine level in peripheral blood in patients with external genital endometriosis.


Assuntos
Ansiedade/sangue , Dor Crônica/sangue , Endometriose/sangue , Histamina/sangue , Dor Pélvica/sangue , Adolescente , Adulto , Ansiedade/psicologia , Dor Crônica/psicologia , Endometriose/psicologia , Feminino , Humanos , Dor Pélvica/psicologia
19.
Trials ; 18(1): 605, 2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29258584

RESUMO

BACKGROUND: The incidence of post-surgical chronic pain ranges between 20% and 40% in Europe. Osteoarthritis pain after prosthesis implantation is one of the most severe secondary syndromes, depending not only on surgery but also on organic changes before and after joints replacement. No data are available about risk factors. An excessive inflammatory response plays a central role but a best therapy is not defined yet. It is not clear whether opioid administration could influence post-surgical pain and lead to tolerance or addiction. Interestingly, the immune system, together with the nervous and peptidergic ones, is involved in hypersensibility. The connection across the three biological systems lies in the presence of opioid receptors on immune cells surface. Here, we show a method to analyze whether opioids could modulate lymphocytes, by proposing opioid receptors as biological markers to prevent chronic pain and opioid tolerance or addiction after hip surgery. METHODS/DESIGN: After institutional independent ethics committee approval, 60 patients, in pain and undergoing hip surgery, will be enrolled in a single-blind, randomized, phase IV, pilot study. Pain treatment will be selected inside a class of non-steroidal anti-inflammatory drugs (NAISDs) or paracetamol or a class of opioids, into three medication arms: 25 mg tapentadol twice daily; 75 mg tapentadol twice daily; NSAIDs or paracetamol in accordance with surgeon's custom. For each group, we will collect blood samples before, during and after surgery, to apply molecular analysis. We will perform lymphocyte opioid receptors genes and proteins expression and functional analysis. Data will be statistically analyzed. DISCUSSION: This project has the potential to obtain a personalized diagnostic kit, by considering lymphocyte opioid receptors as biological markers. Starting from a simple blood sample, it will be possible to decide the best therapy for a single patient. Using a noninvasive approach, we expect to fix a daily standard dose and timing, before and after surgery, to bypass hip chronic pain and the insurgence of tolerance or addiction. The analysis of opioid receptors sensitivity will help to identify the best drug administration in each specific case (tailored therapy). TRIAL REGISTRATION: ISRCTN, ISRCTN12559751 . Retrospectively registered on 23 May 2017.


Assuntos
Analgésicos Opioides/uso terapêutico , Artralgia/prevenção & controle , Artroplastia de Quadril/efeitos adversos , Dor Crônica/prevenção & controle , Tolerância a Medicamentos , Linfócitos/efeitos dos fármacos , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Osteoartrite do Quadril/cirurgia , Dor Pós-Operatória/prevenção & controle , Receptores Opioides/agonistas , Analgésicos Opioides/efeitos adversos , Artralgia/sangue , Artralgia/diagnóstico , Biomarcadores/sangue , Dor Crônica/sangue , Dor Crônica/diagnóstico , Protocolos Clínicos , Humanos , Linfócitos/metabolismo , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/etiologia , Osteoartrite do Quadril/sangue , Osteoartrite do Quadril/diagnóstico , Medição da Dor , Dor Pós-Operatória/sangue , Dor Pós-Operatória/diagnóstico , Projetos Piloto , Receptores Opioides/sangue , Projetos de Pesquisa , Medição de Risco , Fatores de Risco , Gestão de Riscos , Roma , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento
20.
Lipids Health Dis ; 16(1): 112, 2017 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-28606089

RESUMO

BACKGROUND: Chronic widespread pain conditions (CWP) such as the pain associated with fibromyalgia syndrome (FMS) are significant health problems with unclear aetiology. Although CWP and FMS can alter both central and peripheral pain mechanisms, there are no validated markers for such alterations. Pro- and anti-inflammatory components of the immune system such as cytokines and endogenous lipid mediators could serve as systemic markers of alterations in chronic pain. Lipid mediators associated with anti-inflammatory qualities - e.g., oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) - belong to N-acylethanolamines (NAEs). Previous studies have concluded that these lipid mediators may modulate pain and inflammation via the activation of peroxisome proliferator activating receptors (PPARs) and the activation of PPARs may regulate gene transcriptional factors that control the expression of distinct cytokines. METHODS: This study investigates NAEs and cytokines in 17 women with CWP and 21 healthy controls. Plasma levels of the anti-inflammatory lipids OEA, PEA, and SEA, the pro-inflammatory cytokines TNF-α, IL-1ß, IL-6, and IL-8, and the anti-inflammatory cytokine IL-10 were investigated. T-test of independent samples was used for group comparisons. Bivariate correlation analyses, and multivariate regression analysis were performed between lipids, cytokines, and pain intensity of the participants. RESULTS: Significantly higher levels of OEA and PEA in plasma were found in CWP. No alterations in the levels of cytokines existed and no correlations between levels of lipids and cytokines were found. CONCLUSIONS: We conclude that altered levels of OEA and PEA might indicate the presence of systemic inflammation in CWP. In addition, we believe our findings contribute to the understanding of the biochemical mechanisms involved in chronic musculoskeletal pain.


Assuntos
Dor Crônica/sangue , Endocanabinoides/sangue , Etanolaminas/sangue , Fibromialgia/sangue , Ácidos Oleicos/sangue , Ácidos Palmíticos/sangue , Ácidos Esteáricos/sangue , Adulto , Idoso , Anti-Inflamatórios/sangue , Dor Crônica/patologia , Citocinas/sangue , Citocinas/genética , Endocanabinoides/genética , Feminino , Fibromialgia/genética , Estudos de Associação Genética , Humanos , Inflamação/sangue , Inflamação/genética , Inflamação/patologia , Lipídeos/sangue , Lipídeos/genética , Pessoa de Meia-Idade , Ácidos Oleicos/genética
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