Transcranial direct current stimulation is more effective than pregabalin in controlling nociceptive and anxiety-like behaviors in a rat fibromyalgia-like model.

OBJECTIVES: Despite the fact that fibromyalgia, a widespread disease of the musculoskeletal system, has no specific treatment, patients have shown improvement after pharmacological intervention. Pregabalin has demonstrated efficacy; however, its adverse effects may reduce treatment adherence. In this context, neuromodulatory techniques such as transcranial direct current stimulation (tDCS) may be employed as a complementary pain-relieving method. Consequently, the purpose of this study was to evaluate the effect of pregabalin and tDCS treatments on the behavioral and biomarker parameters of rats submitted to a fibromyalgia-like model. METHODS: Forty adult male Wistar rats were divided into two groups: control and reserpine. Five days after the end of the administration of reserpine (1 mg/kg/3 days) to induce a fibromyalgia-like model, rats were randomly assigned to receive either vehicle or pregabalin (30 mg/kg) along with sham or active- tDCS treatments. The evaluated behavioral parameters included mechanical allodynia by von Frey test and anxiety-like behaviors by elevated plus-maze test (time spent in opened and closed arms, number of entries in opened and closed arms, protected head-dipping, unprotected head-dipping [NPHD], grooming, rearing, fecal boluses). The biomarker analysis (brain-derived neurotrophic factor [BDNF] and tumor necrosis factor-α [TNF-α]) was performed in brainstem and cerebral cortex and in serum. RESULTS: tDCS reversed the reduction in the mechanical nociceptive threshold and the decrease in the serum BDNF levels induced by the model of fibromyalgia; however, there was no effect of pregabalin in the mechanical threshold. There were no effects of pregabalin or tDCS found in TNF-α levels. The pain model induced an increase in grooming time and a decrease in NPHD and rearing; while tDCS reversed the increase in grooming, pregabalin reversed the decrease in NPHD. CONCLUSIONS: tDCS was more effective than pregabalin in controlling nociception and anxiety-like behavior in a rat model-like fibromyalgia. Considering the translational aspect, our findings suggest that tDCS could be a potential non-pharmacological treatment for fibromyalgia.

Pain catastrophizing in daughters of women with fibromyalgia: a case-control study.

Fibromyalgia is a syndrome characterized by chronic pain related to the musculoskeletal system. Patients feel incapable and show catastrophic thoughts (exaggeration of the sensations) related to painful events. This study aimed to compare catastrophic thoughts of pain between daughters of women with fibromyalgia and daughters of women without fibromyalgia, no daughter having the syndrome. It was a case-control study in which 76 women were included: 38 daughters of women diagnosed with fibromyalgia (case group), and 38 daughters of women without fibromyalgia (control group). The Brazilian versions of the Profile of Chronic Pain: Screen, the Pittsburgh Sleep Quality Index, the Pain Catastrophizing Scale, Resilience Scale, Beck Depression Inventory-II, and the State-Trait Anxiety Inventory were used. Data were tabulated and analyzed using SPSS 20.0. Continuous variables were compared between the groups using the Mann-Whitney U test or Student's t-test for independent samples. A significant difference was considered at p < 0.05. Regarding catastrophism, the case group had higher total catastrophism compared to the control group (p = 0.025). Daughters of patients with fibromyalgia showed higher rumination and magnification levels related to pain (p = 0.028 and p = 0.007, respectively) but did not show hopelessness. This study concludes that daughters of women with fibromyalgia are more likely to have symptoms of fibromyalgia due to their visualization of the syndrome. This indicates that emotional aspects may induce changes, and additional research on an individual basis is necessary.

Sleep alterations in patients with the human immunodeficiency virus and chronic pain / Alterações do sono em pacientes vivendo com o vírus da imunodeficiência humana e dor crônica

ABSTRACT BACKGROUND AND OBJECTIVES: In patients with chronic pain, insomnia is reported between 50 and 88% of them. It is essential to recognize sleep disorders to estimate its repercussions on the quality of life and to seek knowledge that supports the necessary interventions. This study aims to identify the possible factors that influence sleep quality, as well as its prevalence in these patients. METHODS: Sample consisting of 68 patients (58 women, 10 men), the mean age of 45.3±10.3 years, with a positive diagnosis of human immunodeficiency virus undergoing antiretroviral and chronic pain treatment in Porto Alegre, RS. The Pittsburgh Sleep Quality Index was used to assess the components of the scale as well as their overall score. For the classification of the type of chronic pain, the Leeds Assessment of Neuropathic Symptoms and Signs scale was used, which differentiates nociceptive and neuropathic pain. RESULTS: Patients classified with no pain, nociceptive pain and neuropathic pain. Overall score divided into good sleep, bad sleep and sleep disorder, where patients without pain accounted for 8.8%, 16.2 and 2.9% respectively. With nociceptive pain 4.4, 11.8 and 5.9%, respectively. With neuropathic pain 4.4, 23.5 and 22.1% respectively. Patients with neuropathic pain had the highest rates of poor sleep and sleep disorder, accounting for 50.0% and using more sleeping pills compared to the control group (p<0.05). CONCLUSION: There is a high prevalence of sleep disorders or poor sleep in patients with the human immunodeficiency virus with neuropathic pain. The importance of assessing the sleep as an essential part of the clinical assessment should be recognized and incorporated without delay by health professionals.

RESUMO JUSTIFICATIVA E OBJETIVOS: Em pacientes com dor crônica, a insônia é relatada entre 50 e 88% deles. É fundamental reconhecer as alterações do sono para estimar suas repercussões na qualidade de vida e buscar conhecimentos que respaldem as necessárias intervenções. Este estudo buscou identificar os possíveis fatores que influenciam a qualidade do sono, bem como suas prevalências nesses pacientes. MÉTODOS: Amostra constituída por 68 pacientes (58 mulheres e 10 homens) com idade média de 45,3±10,3 anos, diagnóstico positivo para o vírus da imunodeficiência humana em tratamento antirretroviral e dor crônica, de uma instituição em Porto Alegre, RS. O Questionário do Índice de Qualidade de Sono de Pittsburgh foi usado para a avaliação dos componentes da escala de sono, bem como sua pontuação total. Para a classificação do tipo de dor crônica foi utilizada a escala Leeds Assessment of Neuropathic Symptoms and Signs, que diferencia dor nociceptiva e neuropática. RESULTADOS: Os pacientes foram classificados em sem dor, dor nociceptiva e dor neuropática. A pontuação global foi dividida em sono bom, sono ruim e distúrbio do sono, onde os pacientes sem dor representaram 8,8, 16,2 e 2,9% respectivamente. Com dor nociceptiva 4,4, 11,8 e 5,9% respectivamente. Com dor neuropática 4,4, 23,5 e 22,1% respectivamente. Os pacientes com dor neuropática apresentaram os maiores índices de sono ruim e distúrbio do sono, representando 50,0% e utilizavam mais fármacos para dormir em comparação com o grupo controle (p<0,05). CONCLUSÃO: Existe elevada prevalência de distúrbios do sono ou sono ruim em pacientes portadores do vírus com dor neuropática. A importância da avaliação do sono como parte essencial da avaliação clínica deve ser reconhecida e incorporada sem demora pelos profissionais de saúde.

Potency of descending pain modulatory system is linked with peripheral sensory dysfunction in fibromyalgia: An exploratory study.

Fibromyalgia (FM) is characterized by chronic widespread pain whose pathophysiological mechanism is related to central and peripheral nervous system dysfunction. Neuropathy of small nerve fibers has been implicated due to related pain descriptors, psychophysical pain, and neurophysiological testing, as well as skin biopsy studies. Nevertheless, this alteration alone has not been previously associated to the dysfunction in the descending pain modulatory system (DPMS) that is observed in FM. We hypothesize that they associated, thus, we conducted a cross-sectional exploratory study.To explore small fiber dysfunction using quantitative sensory testing (QST) is associated with the DPMS and other surrogates of nociceptive pathways alterations in FM.We run a cross-sectional study and recruited 41 women with FM, and 28 healthy female volunteers. We used the QST to measure the thermal heat threshold (HTT), heat pain threshold (HPT), heat pain tolerance (HPT), heat pain tolerance (HPTo), and conditional pain modulation task (CPM-task). Algometry was used to determine the pain pressure threshold (PPT). Scales to assess catastrophizing, anxiety, depression, and sleep disturbances were also applied. Serum brain-derived neurotrophic factor (BDNF) was measured as a marker of neuroplasticity. We run multivariate linear regression models by group to study their relationships.Samples differed in their psychophysical profile, where FM presented lower sensitivity and pain thresholds. In FM but not in the healthy subjects, regression models revealed that serum BDNF was related to HTT and CPM-Task (Hotelling Trace = 1.80, P < .001, power = 0.94, R = 0.64). HTT was directly related to CPM-Task (B = 0.98, P = .004, partial-η = 0.25), and to HPT (B = 1.61, P = .008, partial η = 0.21), but not to PPT. Meanwhile, BDNF relationship to CPM-Task was inverse (B = -0.04, P = .043, partial-η = 0.12), and to HPT was direct (B = -0.08, P = .03, partial-η = 0.14).These findings high spot that in FM the disinhibition of the DPMS is positively correlated with the dysfunction in peripheral sensory neurons assessed by QST and conversely with serum BDNF.

Novel Insights of Effects of Pregabalin on Neural Mechanisms of Intracortical Disinhibition in Physiopathology of Fibromyalgia: An Explanatory, Randomized, Double-Blind Crossover Study.

Background: The fibromyalgia (FM) physiopathology involves an intracortical excitability/inhibition imbalance as measured by transcranial magnetic stimulation measures (TMS). TMS measures provide an index that can help to understand how the basal neuronal plasticity state (i.e., levels of the serum neurotrophins brain-derived neurotrophic factor (BDNF) and S100-B protein) could predict the effect of therapeutic approaches on the cortical circuitries. We used an experimental paradigm to evaluate if pregabalin could be more effective than a placebo, to improve the disinhibition in the cortical circuitries in FM patients, than in healthy subjects (HS). We compared the acute intragroup effect of pregabalin with the placebo in FM patients and healthy subjects (HS) on the current silent period (CSP) and short intracortical inhibition (SICI), which were the primary outcomes. Pain scores and the pain pressure threshold (PPT) were secondary outcomes. Methods: This study included 27 women (17 FM and 10 HS), with ages ranging from 19 to 65 years. In a blinded, placebo-controlled clinical trial, participants were randomized to receive, in a cross-over manner, oral pregabalin of 150 mg or a placebo. The cortical excitability pain measures were assessed before and 90 min after receiving the medication. Results: A generalized estimating equation (GEE) model revealed that in FM, pregabalin increased the CSP by 14.34% [confidence interval (CI) 95%; 4.02 to 21.63] and the placebo reduced the CSP by 1.58% (CI 95%; -57 to 25.9) (P = 0.00). Pregabalin reduced the SICI by 8.82% (CI 95%, -26 to 46.00) and the placebo increased it by 19.56% (CI 95%; 8.10 to 59.45; P = 0.02). Pregabalin also improved the pain measures. In the treatment group, the BDNF-adjusted index was positively correlated and the serum S100-B negatively correlated with the CSP, respectively. However, in the HS, pregabalin and the placebo did not induce a statistically significant effect in either intracortical excitability or pain measures. Conclusion: These results suggest that pregabalin's effect on cortical neural networks occurs, particularly under basal neuronal hyperexcitability, because its impact on the cortical excitability and the pain measures was observed only in the FM group. This indicates that pregabalin increased the CSP to induce inhibition in specific neural networks, while it increased the SICI to improve the excitability in other neurobiological systems. Trial registration in clinicaltrials.gov Identifier: NCT02639533.

Predictors of in-hospital mortality in patients undergoing elective surgery in a university hospital: a prospective cohort / Preditores de mortalidade intra-hospitalar em pacientes submetidos a cirurgias não eletivas em um hospital universitário: uma coorte prospectiva

Abstract Introduction Morbidity and mortality associated with urgent or emergency surgeries are high compared to elective procedures. Perioperative risk scores identify the non-elective character as an independent factor of complications and death. The present study aims to characterize the population undergoing non-elective surgeries at the Hospital de Clínicas de Porto Alegre and identify the clinical and surgical factors associated with death within 30 days postoperatively. Methodology A prospective cohort study of 187 patients undergoing elective surgeries between April and May 2014 at the Hospital de Clínicas, Porto Alegre. Patient-related data, pre-operative risk situations, and surgical information were evaluated. Death in 30 days was the primary outcome measured. Results The mean age of the sample was 48.5 years, and 84.4% of the subjects had comorbidities. The primary endpoint was observed in 14.4% of the cases, with exploratory laparotomy being the procedure with the highest mortality (47.7%). After multivariate logistic regression, age (odds ratio [OR] 1.0360, p < 0.05), anemia (OR 3.961, p < 0.05), acute or chronic renal insufficiency (OR 6.075, p < 0.05), sepsis (OR 7.027, p < 0.05), and patient-related risk factors for mortality, in addition to the large surgery category (OR 7.502, p < 0.05) were identified. Conclusion The high mortality rate found may reflect the high complexity of the institution's patients. Knowing the profile of the patients assisted helps in the definition of management priorities, suggesting the need to create specific care lines for groups identified as high risk in order to reduce perioperative complications and deaths.

Resumo Introdução Quando comparada a procedimentos eletivos, a morbimortalidade associada às cirurgias de urgência ou emergência é alta. Escores de risco perioperatório identificam o caráter não eletivo como fator independente de complicações e morte. O presente estudo objetiva caracterizar a população submetida a cirurgias não eletivas no Hospital de Clínicas de Porto Alegre e identificar fatores clínicos e cirúrgicos associados à morte em 30 dias no pós-operatório. Metodologia Coorte prospectiva de 187 pacientes submetidos a cirurgias não eletivas entre abril e maio de 2014 no Hospital de Clínicas de Porto Alegre. Avaliaram-se dados relacionados ao paciente, situações de risco pré-operatórias e informações do âmbito cirúrgico. Mensurou-se óbito em 30 dias como desfecho primário. Resultados A média de idade da amostra foi 48,5 anos; 84,4% dos indivíduos apresentavam comorbidades. O desfecho primário foi observado em 14,4% dos casos, laparotomia exploradora foi o procedimento com maior mortalidade (47,7%). Após regressão logística multivariada, identificaram-se idade (odds ratio [OR] 1.0360, p < 0,05), anemia (OR 3.961, p < 0,05), insuficiência renal aguda ou crônica agudizada (OR 6.075, p < 0,05) e sepse (OR 7.027, p < 0,05) como os fatores de risco relacionados ao paciente significativos para mortalidade, além da categoria cirurgia de grande porte (OR 7.502, p < 0,05). Conclusão A elevada taxa de mortalidade encontrada pode refletir a alta complexidade dos pacientes da instituição. O conhecimento do perfil dos pacientes atendidos auxilia na definição de prioridades de gerenciamento, sugere a necessidade de criação de linhas de cuidado específicas para grupos identificados como de alto risco, a fim de reduzir complicações e óbitos no perioperatório.

[Predictors of in-hospital mortality in patients undergoing elective surgery in a university hospital: a prospective cohort]. / Preditores de mortalidade intra­hospitalar em pacientes submetidos a cirurgias não eletivas em um hospital universitário: uma coorte prospectiva.

INTRODUCTION: Morbidity and mortality associated with urgent or emergency surgeries are high compared to elective procedures. Perioperative risk scores identify the non-elective character as an independent factor of complications and death. The present study aims to characterize the population undergoing non-elective surgeries at the Hospital de Clínicas de Porto Alegre and identify the clinical and surgical factors associated with death within 30 days postoperatively. METHODOLOGY: A prospective cohort study of 187 patients undergoing elective surgeries between April and May 2014 at the Hospital de Clínicas, Porto Alegre. Patient-related data, pre-operative risk situations, and surgical information were evaluated. Death in 30 days was the primary outcome measured. RESULTS: The mean age of the sample was 48.5 years, and 84.4% of the subjects had comorbidities. The primary endpoint was observed in 14.4% of the cases, with exploratory laparotomy being the procedure with the highest mortality (47.7%). After multivariate logistic regression, age (odds ratio [OR] 1.0360, p <0.05), anemia (OR 3.961, p <0.05), acute or chronic renal insufficiency (OR 6.075, p <0.05), sepsis (OR 7.027, p <0.05), and patient-related risk factors for mortality, in addition to the large surgery category (OR 7.502, p <0.05) were identified. CONCLUSION: The high mortality rate found may reflect the high complexity of the institution's patients. Knowing the profile of the patients assisted helps in the definition of management priorities, suggesting the need to create specific care lines for groups identified as high risk in order to reduce perioperative complications and deaths.

Motor Cortex Excitability and BDNF Levels in Chronic Musculoskeletal Pain According to Structural Pathology.

The central sensitization syndrome (CSS) encompasses disorders with overlapping symptoms in a structural pathology spectrum ranging from persistent nociception [e.g., osteoarthritis (OA)] to an absence of tissue injuries such as the one presented in fibromyalgia (FM) and myofascial pain syndrome (MPS). First, we hypothesized that these syndromes present differences in their cortical excitability parameters assessed by transcranial magnetic stimulation (TMS), namely motor evoked potential (MEP), cortical silent period (CSP), short intracortical inhibition (SICI) and short intracortical facilitation (SICF). Second, considering that the presence of tissue injury could be detected by serum neurotrophins, we hypothesized that the spectrum of structural pathology (i.e., from persistent nociception like in OA, to the absence of tissue injury like in FM and MPS), could be detected by differential efficiency of their descending pain inhibitory system, as assessed by the conditioned pain modulation (CPM) paradigm. Third, we explored whether brain-derived neurotrophic factor (BDNF) had an influence on the relationship between motor cortex excitability and structural pathology. This cross-sectional study pooled baseline data from three randomized clinical trials. We included females (n = 114), aged 19-65 years old with disability by chronic pain syndromes (CPS): FM (n = 19), MPS (n = 54), OA (n = 27) and healthy subjects (n = 14). We assessed the serum BDNF, the motor cortex excitability by parameters the TMS measures and the change on numerical pain scale [NPS (0-10)] during CPM-task. The adjusted mean (SD) on the SICI observed in the absence of tissue injury was 56.36% lower than with persistent nociceptive input [0.31(0.18) vs. 0.55 (0.32)], respectively. The BDNF was inversely correlated with the SICI and with the change on NPS (0-10)during CPM-task. These findings suggest greater disinhibition in the motor cortex and the descending pain inhibitory system in FM and MPS than in OA and healthy subjects. Likewise, the inter-hemispheric disinhibition as well as the dysfunction in the descending pain modulatory system is higher in chronic pain without tissue injury compared to a structural lesion. In addition, they suggest that a greater level of serum BDNF may be involved in the processes that mediate the disinhibition of motor cortex excitability, as well as the function of descending inhibitory pain modulation system, independently of the physiopathology mechanism of musculoskeletal pain syndromes.

Caffeine teratogenicity in rats: morphological characterization and hypothesized mechanisms

Caffeine consumption during pregnancy has been shown in the scientific literature to be associated with teratogenicity such as low birth weight, fetal malformations, and miscarriage. However, the morphological alterations of the offspring of dams exposed during pregnancy have not been consistently described, and the mechanisms why they occur remain elusive. Thus, we aimed to characterize the offspring malformations induced by moderate and high doses of caffeine during pregnancy. Dams were divided into three groups: control, moderate (0.3 g/L), and high dose (1.0 g/L) of caffeine, which was provided in the drinking water beginning on gestational day 1 and continuing throughout the entire gestation. At moderate doses, only one of the dams had stillborn pups, although no macroscopic malformations were observed. High doses of caffeine induced significantly more malformations (P<0.001) and early death (before P4). The malformations observed were related to fetal development and cardiovascular alterations, namely bruises, macrocephaly with short limbs, abnormal development (or absence) of head structures and limbs, labial malformations, hydrops fetalis, and poor placental formation. We discussed the proposed mechanisms by which caffeine might induce these phenotypes, which may involve down-regulation of adenosine A1 receptors, and increased mothers' catecholamines. Our findings further confirm the evidence of the teratogenic effects of high doses of caffeine administered during pregnancy. These findings support the recommendation to avoid caffeine exposure during pregnancy (AU)

Dor neuropática em pacientes com HIV/AIDS em uso de terapia antirretroviral / Neuropathic pain in HIV/AIDS patients using antiretroviral therapy

A infecção pelo vírus da imunodeficiência humana (HIV) representa um dos maiores problemas de saúde da atualidade em virtude de seu caráter pandêmico e gravidade. O uso da terapia antirretroviral está associado ao desenvolvimento de diferentes tipos de dor, sendo a dor neuropática uma delas. A dor neuropática ocorre pela lesão do sistema nociceptivo, que envolve mudanças moleculares, fisiológicas e anatômicas. Considerando que a infecção por HIV gera custos elevados para o sistema de saúde, e que suas comorbidades elevam ainda mais esses custos, a compreensão dos mecanismos da dor nessa população possibilita uma melhor assistência e uma redução da carga para o sistema. A dor neuropática pode apresentar diferentes possíveis mecanismos fisiopatológicos envolvidos, tornando-se um desafio para o tratamento de pacientes com HIV. A compreensão sobre a neurofisiologia da dor neuropática e o HIV pode promover melhores abordagens aos pacientes e a redução de comorbidades associadas, com impacto na qualidade de vida (AU)

Human immunodeficiency virus (HIV) infection is a major health problem nowadays due to its pandemic character and severity. The use of antiretroviral therapy is associated with the development of different types of pain, and neuropathic pain is one of them. Neuropathic pain is caused by an injury to the nociceptive system, which involves molecular, physiological and anatomical changes. Considering that HIV infection generates high costs for the health system, and that its comorbidities raise such costs even more, understanding the mechanisms of pain in this population can result in better care practices and reduction of burden to the system. Neuropathic pain may present different pathophysiological mechanisms becoming a challenge for HIV treatment. The understanding of the neurophysiology of neuropathic pain and the HIV can promote better patient approaches and the reduction of associated comorbidities with an impact on quality of life (AU)

Neonatal hypoxic-ischemic encephalopathy reduces c-Fos activation in the rat hippocampus: evidence of a long-lasting effect.

The effect of neonatal hypoxic-ischemic encephalopathy (HIE) on maturation of nociceptive pathways has been sparsely explored. To investigate whether neonatal HIE alters neuronal activity, nociceptive behavior, and serum neuroplasticity mediators (brain-derived neurotrophic factor [BDNF] and tumor necrosis factor-α [TNF]) in the short, medium, and long term. Neonate male Wistar rats were randomized to receive a brain insult that could be either ischemic (left carotid artery ligation [LCAL]), hypoxic (8% oxygen chamber), hypoxic-ischemic (LCAL and hypoxic chamber), sham-ischemic, or sham-hypoxic. Neuronal activity (c-Fos activation at region CA1 and dentate gyrus of the hippocampus), nociceptive behavior (von Frey, tail-flick, and hot-plate tests), neuroplasticity mediators (BDNF, TNF), and a cellular injury marker (lactase dehydrogenase [LDH]) were assessed in blood serum 14, 30, and 60 days after birth. Neonatal HIE persistently reduced c-Fos activation in the ipsilateral hippocampal region CA1; however, contralateral c-Fos reduction appeared only 7 weeks after the event. Neonatal HIE acutely reduced the paw withdrawal threshold (von Frey test), but this returned to normal by the 30th postnatal day. Hypoxia reduced serum LDH levels. Serum neuroplasticity mediators increased with age, and neonatal HIE did not affect their ontogeny. Neonatal HIE-induced reduction in neuronal activity occurs acutely in the ipsilateral hippocampal region CA1 and persists for at least 60 days, but the contralateral effect of the insult is delayed. Alterations in the nociceptive response are acute and self-limited. Serum neuroplasticity mediators increase with age, and remain unaffected by HIE.

Higher serum S100B and BDNF levels are correlated with a lower pressure-pain threshold in fibromyalgia.

BACKGROUND: Fibromyalgia (FM) is conceptualized as a central sensitization (CS) condition, that presents high serum brain-derived neurotrophic factor (BDNF) and neuroglia activation. Although the S100B protein regulates neuroglia functions, it has been traditionally used as a proxy of central nervous system damage. However, neither BDNF nor S100B association with the clinical picture of FM has been elucidated. To explore their association with the pressure-pain threshold (PPT) in FM, we performed a cross-sectional study, including 56 females with confirmed FM aged 18-65 years. Linear regression models were used to adjust for potential confounding factors between serum BDNF, S100B and PPT. RESULTS: Serum BDNF and S100B were correlated (Spearman's Rho = 0.29). Serum BDNF (log) and S100B (log) were correlated with the PPT (log) (Partial η2 = 0.129, P = 0.012 for the BDNF (log), and Partial η2 = 0.105, P = 0.025 for the S100B (log)). Serum BDNF (log) was inversely associated with PPT (log) (ß = -1.01, SE = 0.41), age (ß = -0.02, SE = 0.15) and obsessive compulsive disorder (ß = -0.36, SE = 0.15), while serum S100B (log) was inversely associated with PPT (log) (ß = -1.38, SE = 0.50), only. CONCLUSIONS: Both neuroglia key mediators in the CS process were inversely correlated with the PPT. Serum assessment of BDNF and S100B deserve further study to determine its potential as a proxy for the CS spectrum in FM.