Epigenetics insights into chronic pain: DNA hypomethylation in fibromyalgia-a controlled pilot-study.

To evaluate changes in DNA methylation profiles in patients with fibromyalgia (FM) compared to matched healthy controls (HCs). All individuals underwent full clinical and neurophysiological assessment by cortical excitability (CE) parameters measured by transcranial magnetic stimulation. DNA from the peripheral blood of patients with FM (n = 24) and HC (n = 24) were assessed using the Illumina-HumanMethylation450 BeadChips. We identified 1610 differentially methylated positions (DMPs) in patients with FM displaying a nonrandom distribution in regions of the genome. Sixty-nine percent of DMP in FM were hypomethylated compared to HC. Differentially methylated positions were enriched in 5 genomic regions (1p34; 6p21; 10q26; 17q25; 19q13). The functional characterization of 960 genes related to DMPs revealed an enrichment for MAPK signaling pathway (n = 18 genes), regulation of actin cytoskeleton (n = 15 genes), and focal adhesion (n = 13 genes). A gene-gene interaction network enrichment analysis revealed the participation of DNA repair pathways, mitochondria-related processes, and synaptic signaling. Even though DNA was extracted from peripheral blood, this set of genes was enriched for disorders such as schizophrenia, mood disorders, bulimia, hyperphagia, and obesity. Remarkably, the hierarchical clusterization based on the methylation levels of the 1610 DMPs showed an association with neurophysiological measurements of CE in FM and HC. Fibromyalgia has a hypomethylation DNA pattern, which is enriched in genes implicated in stress response and DNA repair/free radical clearance. These changes occurred parallel to changes in CE parameters. New epigenetic insights into the pathophysiology of FM may provide the basis for the development of biomarkers of this disorder.

The influence of depression on personality traits in patients with fibromyalgia: a case-control study.

OBJECTIVES: We developed this study to investigate the association of fibromyalgia with personality traits, controlling for depression and other potential confounders. METHODS: We assessed personality traits using the Cloninger's Temperament and Character Inventory (TCI) in 78 female patients with fibromyalgia and in a control group of 78 subjects without fibromyalgia. The Mini-International Neuropsychiatric Interview was used to assess depression and anxiety diagnoses. To investigate the association between fibromyalgia and the Cloninger's Temperament and Character Inventory we performed unadjusted and adjusted analyses of covariance, using the TCI score as dependent variable and adjusting the model for depression, anxiety and for clinical and socio-demographic variables. We used a backward selection method to choose the final model. RESULTS: In the unadjusted analysis, fibromyalgia was associated with all personality traits, except persistency. After adjusting for depression and anxiety, patients with fibromyalgia presented decreased novelty seeking compared to controls; the differences in other personality traits were no longer significant. Novelty seeking was also correlated with the length of history of fibromyalgia and pain intensity. CONCLUSIONS: Decreased novelty seeking may be a personality trait associated with fibromyalgia. Depression and anxiety should be considered potential confounders in the evaluation of personality traits in this population.

Depression, sexuality and fibromyalgia syndrome: clinical findings and correlation to hematological parameters.

OBJECTIVE: To investigate sexuality and depression in women with FM compared with controls and to correlate the findings with hematological parameters. METHODS: 33 women with FM and 19 healthy women were included and evaluated with the following instruments: Female Sexual Function Index, Beck Inventory, Visual Analogue Scale, medical history and laboratory exams. RESULTS: The prevalence of sexual dysfunction (P = 0.007) and depression (P < 0.001) were higher in the study group than in the control group; they were positively correlated (P = 0.023). The study group showed lower serum concentrations of testosterone, free T4, antinuclear factor, and lower blood hemoglobin and hematocrit. CONCLUSIONS: FM was associated with high scores of sexual dysfunction and depression, and there were correlations with hematological parameters. We suggest the involvement of immune-inflammatory mediators and FM, which need further investigation to understand their role in FM syndrome and its comorbidities.

Depression, sexuality and fibromyalgia syndrome: clinical findings and correlation to hematological parameters / Depressão e sexualidade na síndrome fibromiálgica: achados clínicos e correlação com parâmetros hematológicos

ABSTRACT Fibromyalgia (FM) is characterized by chronic pain and comorbidities. Objective To investigate sexuality and depression in women with FM compared with controls and to correlate the findings with hematological parameters. Methods 33 women with FM and 19 healthy women were included and evaluated with the following instruments: Female Sexual Function Index, Beck Inventory, Visual Analogue Scale, medical history and laboratory exams. Results The prevalence of sexual dysfunction (P = 0.007) and depression (P < 0.001) were higher in the study group than in the control group; they were positively correlated (P = 0.023). The study group showed lower serum concentrations of testosterone, free T4, antinuclear factor, and lower blood hemoglobin and hematocrit. Conclusions FM was associated with high scores of sexual dysfunction and depression, and there were correlations with hematological parameters. We suggest the involvement of immune-inflammatory mediators and FM, which need further investigation to understand their role in FM syndrome and its comorbidities.

RESUMO Fibromialgia (FS) é caracterizada por dor e comorbidades. Objetivo investigar depressão e sexualidade em mulheres com FS comparadas a controles, e correlacionar os achados com parâmetros hematológicos. Métodos 33 mulheres com FS e 19 controles saudáveis foram incluídas e avaliadas através dos seguintes instrumentos: Índice de Função Feminina Sexual, Inventário de Beck, escala visual analógica, história médica e exames laboratoriais. Resultados A prevalência de disfunção sexual (P = 0,007) e depressão (P < 0,001) foram maiores no grupo de estudo do que nos controles; também houve correlação positiva (P = 0,023). O grupo de estudo apresentou menor concentração sérica de testosterona, T4 livre, fator antinuclear e menos concentração de hemoglobina e hematócrito. Conclusões A FS associou-se com altos índices de disfunção sexual e depressão, e houve correlação com os parâmetros hematológicos estudados. Sugere-se o envolvimento de mediadores imuno-inflamatórios na FS, que necessita de maior investigação para a compreensão dos mecanismos tanto na FS e quanto em suas comorbidades.

Repetitive transcranial magnetic stimulation in chronic pain: a review of the literature.

OBJECTIVE: To review the literature on the analgesic effects of repetitive transcranial magnetic stimulation (rTMS) in chronic pain according to different pain syndromes and stimulation parameters. DATA SOURCES: Publications on rTMS and chronic pain were searched in PubMed and Google Scholar using the following key words: chronic pain, analgesia, transcranial magnetic stimulation, neuropathic pain, fibromyalgia, and complex regional pain syndrome. STUDY SELECTION: This review only included double-blind, controlled studies with >10 participants in each arm that were published from 1996 to 2014 and written in English. Studies with relevant information for the understanding of the effects of rTMS were also cited. DATA EXTRACTION: The following data were retained: type of pain syndrome, type of study, coil type, target, stimulation intensity, frequency, number of pulses, orientation of induced current, number of session, and a brief summary of intervention outcomes. DATA SYNTHESIS: A total of 33 randomized trials were found. Many studies reported significant pain relief by rTMS, especially high-frequency stimulation over the primary motor cortex performed in consecutive treatment sessions. Pain relief was frequently >30% compared with control treatment. Neuropathic pain, fibromyalgia, and complex regional pain syndrome were the pain syndromes more frequently studied. However, among all published studies, only a few performed repetitive sessions of rTMS. CONCLUSIONS: rTMS has potential utility in the management of chronic pain; however, studies using maintenance sessions of rTMS and assessing the effects of rTMS on the different aspects of chronic pain are needed to provide a more solid basis for its clinical application for pain relief.

Psychometric validation of the Portuguese version of the Neuropathic Pain Symptoms Inventory.

BACKGROUND: It has been shown that different symptoms or symptom combinations of neuropathic pain (NeP) may correspond to different mechanistic backgrounds and respond differently to treatment. The Neuropathic Pain Symptom Inventory (NPSI) is able to detect distinct clusters of symptoms (i.e. dimensions) with a putative common mechanistic background. The present study described the psychometric validation of the Portuguese version (PV) of the NPSI. METHODS: Patients were seen in two consecutive visits, three to four weeks apart. They were asked to: (i) rate their mean pain intensity in the last 24 hours on an 11-point (0-10) numerical scale; (ii) complete the PV-NPSI; (iii) provide the list of pain medications and doses currently in use. VAS and Global Impression of Change (GIC) were filled out in the second visit. RESULTS: PV-NPSI underwent test-retest reliability, factor analysis, analysis of sensitivity to changes between both visits. The PV-NPSI was reliable in this setting, with a good intra-class correlation for all items. The factorial analysis showed that the PV-NPSI inventory assessed different components of neuropathic pain. Five different factors were found. The PV-NPSI was adequate to evaluate patients with neuropathic pain and to detect clusters of NeP symptoms. CONCLUSIONS: The psychometric properties of the PV-NPSI rendered it adequate to evaluate patients with both central and peripheral neuropathic pain syndromes and to detect clusters of NeP symptoms.

A randomized controlled trial of acupuncture added to usual treatment for fibromyalgia.

OBJECTIVE: To evaluate the effectiveness of acupuncture for fibromyalgia. METHODS: Fifty-eight women with fibromyalgia were allocated randomly to receive either acupuncture together with tricyclic antidepressants and exercise (n=34), or tricyclic antidepressants and exercise only (n=24). Patients rated their pain on a visual analogue scale. A blinded assessor evaluated both the mean pressure pain threshold value over all 18 fibromyalgia points and quality of life using SF-36. RESULTS: At the end of 20 sessions, patients who received acupuncture were significantly better than the control group in all measures of pain and in 5 of the SF-36 subscales. After 6 months, the acupuncture group was significantly better than the control group in numbers of tender points, mean pressure pain threshold at the 18 tender points and 3 subscales of SF-36. After one year, the acupuncture group showed significance in one subscale of the SF-36; at 2 years there were no significant differences in any outcome measures. CONCLUSION: Addition of acupuncture to usual treatments for fibromyalgia may be beneficial for pain and quality of life for 3 months after the end of treatment. Future research is needed to evaluate the specific effects of acupuncture for fibromyalgia.

Impact of nervous system hyperalgesia on pain, disability, and quality of life in patients with knee osteoarthritis: a controlled analysis.

OBJECTIVE: Refractory, disabling pain associated with knee osteoarthritis (OA) is usually treated with total knee replacement. However, pain in these patients might be associated with central nervous sensitization rather than peripheral inflammation and injury. We evaluated the presence of hyperalgesia in patients scheduled for a total knee replacement due to knee osteoarthritis with refractory pain, and we assessed the impact of pressure pain threshold measurements (PPT) on pain, disability, and quality of life of these patients. METHODS: Sixty-two female patients were compared with 22 age-matched healthy controls without reported pain for the last year. PPT was measured at the lower extremities subcutaneous dermatomes, over the vastus medialis, adductor longus, rectus femoris, vastus lateralis, tibialis anterior, peroneus longus, iliacus, quadratus lumborum and popliteus muscles and at the supraspinous ligaments from L1-L5, over the L5-S1 and S1-S2 sacral areas and at the pes anserinus bursae and patellar tendon. RESULTS: Patients with knee OA had significantly lower PPT over all evaluated structures versus healthy control subjects (P<0.001). Lower PPT values were correlated with higher pain intensity, higher disability scores, and with poorer quality of life, except for the role-emotional and general health status. Combined PPT values over the patellar tendon, at the S2 subcutaneous dermatome and at the adductor longus muscle were the best predictors for visual analog scale and Western Ontario and McMaster Universities Osteoarthritis Index pain scores. CONCLUSION: Patients with pain due to osteoarthritis who were scheduled for total knee replacement showed hyperalgesia of nervous system origin that negatively impacted pain, knee functional capacity, and most aspects of quality of life.

Pain treatment with acupuncture for patients with fibromyalgia.

Fibromyalgia is a chronic, painful musculoskeletal syndrome of unknown etiopathogenesis. In addition to medicamentous and physical and psychologic therapies, several other adjunct therapies have been used as alternatives in the attempt to obtain analgesia and decrease the symptoms that are characteristic of this problem. This article presents a literary review on the use of acupuncture as an adjunct or chief treatment for patients with fibromyalgia, comparing it with an ongoing clinical experience that has been carried out at Hospital das Clínicas in the city of São Paulo. The results were found by applying traditional acupuncture, which demonstrated positive rates in the Visual Analogue Scale, myalgic index, number of tender points, and improvement in quality of life based on the SF-36 questionnaire.

Fibromialgia x Síndrome dolorosa miofascial

Fibromialgia uma síndrome dolorosa crônica caracterizada pela presença de dores generalizadas e difusas; presença de pontos dolorosos específicos á palpaçäo denominados tender points (TePs). Ela pode ser classificada em: fibromialgia regional, primária, secundária e concomitante. A fibromialgia regional é também denominada fibromialgia localizada e síndrome dolorosa miofascial, isto é, os sintomas dolorosos têm localizaçäo regional. A fibromialgia primária é caracterizada pela presença de dor difusa generalizada e com múltiplos tender pointse, na falta de patologia de base ou concomitante, explicaria os sinais e sintomas da dor parcial ou total do sitema músculo-esquelético.

Dor miofascial em pacientes com osteoartrose do quadril / Myofascial pain in patients with osteoarthritis of the hip

A osteoartrose (OA) do quadril é uma doença de alta prevalência, especialmente nas faixas etárias mais avançadas. Seu tratamento por meio da artroplastia tem resultados muito satisfatórios näo apenas no que concerne a dor mas também em termos de melhora funcional. Contudo, diante da presença também elevada de outras afecçöes que complicam o procedimento anestésico e o acompanhamento pós-operatório, o uso de alternativas terapêuticas menos invasivas é recomendável, sendo, por vezes, a única forma restante de tratamento, mesmo que apenas paliativo. A investigaçäo de outras causas de dor e incapacidade nestes pacientes é uma obrigaçäo do médico preocupado com o bem-estar destes pacientes. Neste artigo faremos uma breve revisäo da aspectos clínicos da osteoartrose do quadril e proporemos uma nova abordagem, tendo em vista a pesquisa de pontos dolorosos relacionados à síndrome dolorosa miofascial.