Cognitive function in patients with chronic pain treated with opioids: characteristics and associated factors

Background The paucity of studies regarding cognitive function in patients with chronic pain, and growing evidence regarding the cognitive effects of pain and opioids on cognitive function prompted us to assess cognition via neuropsychological measurement in patients with chronic non-cancer pain treated with opioids. Methods In this cross-sectional study, 49 patients were assessed by Continuous Reaction Time, Finger Tapping, Digit Span, Trail Making Test-B and Mini-mental State Examination tests. Linear regressions were applied. Results Patients scored poorly in the Trail Making Test-B (mean?=?107.6?s, SD?=?61.0, cut-off?=?91?s); and adequately on all other tests. Several associations among independent variables and cognitive tests were observed. In the multiple regression analyses, the variables associated with statistically significant poor cognitive performance were female sex, higher age, lower annual income, lower schooling, anxiety, depression, tiredness, lower opioid dose, and more than 5?h of sleep the night before assessment (P?<?0.05). Conclusions Patients with chronic pain may have cognitive dysfunction related to some reversible factors, which can be optimized by therapeutic interventions.

Signs and Symptoms of Temporomandibular Dysfunction in Fibromyalgic Patients

Objective: The objective of this study was to determine the frequency of signs and symptoms of temporomandibular disorder (TMD) in fibromyalgic patients. Methods: Sixty subjects of both sexes (mean age, 49.2 +/- 13.8 years) with fibromyalgia (FM) diagnosis were included in this study. All patients were examined by a calibrated investigator to identify the presence of TMD using the Research Diagnostic Criteria for TMD. Results: The most common signs (A) and symptoms (B) reported by FM patients were (A) pain in the masticatory muscles (masseter, 80%; posterior digastric, 76.7%), pain in the temporomandibular joint (83.3%), and 33.3% and 28.3%, respectively, presented joint sounds when opening and closing the mouth; (B) headache (97%) and facial pain (81.7%). In regard to the classic triad for the diagnosis of the TMD, it was found that 35% of the FM patients presented, at the same time, pain, joint sounds, and alteration of the mandibular movements. It was verified that myofascial pain without limitation of mouth opening was the most prevalent diagnosis (47%) for the RDC subgroup I. For the subgroup II, the disk displacement with reduction was the most prevalent diagnosis (21.6%). For the subgroup III, 36.7% of the subjects presented osteoarthritis. Conclusions: Thus, there is a high prevalence of signs and symptoms of TMD in FM patients, indicating the need for an integrated diagnosis and treatment of these patients, which suggest that the FM could be a medium- or long-term risk factor for the development of TMD.

Videofluoroscopic evaluation of mastication and swallowing in individuals with TMD

To study mastication and swallowing disorders in patients with temporomanclibular disorders (TMD). Objective: To investigate mastication and swallowing disorders in patients with severe TMD referred to surgery. Materials and Methods: Clinical and experimental study involving ten individuals with TMD submitted to deglutition videofluoroscopy. These patients did not have posterior teeth, mastication pain and food replacement in favor of pasty consistence food. The assessment of the oral and pharyngeal phases approached the following aspects: side of onset and preferential side for chewing, premature escape, remains of food residues in the oral cavity or in the pharyngeal recesses, number of necessary swallowing efforts, laryngeal penetration and/or tracheal aspiration. Results: During mastication and the oral phase we observed tongue compensatory movements upon chewing (n = 7; 70%), premature escape (n = 4; 40%), food remains in the cavity after swallowing (n = 5; 50%) and an excessive number of deglutition efforts (n = 5; 50%). On the pharyngeal phase we observed food remains in the valleculae (n = 6; 60%), in the pyriform sinuses (n = 4; 40%); laryngeal penetration (n = 1; 10%) and tracheal aspiration (n = 4; 40%). Conclusion: TMD patients may have alterations in their chewing and swallowing patterns, with laryngeal penetration and/or tracheal aspiration. The study indicates the need for a multidisciplinary assessment because of dysphagia in TMD patients.

Early and late neurodegeneration and memory disruption after intracerebroventricular streptozotocin

Glucose metabolism and insulin signaling disruptions in the brain have been proposed as a likely etiology of Alzheimer's disease. The aim of the present study was to investigate the time course of cognitive impairments induced by intracerebroventricular injection of streptozotocin (STZ) in rats and correlate them with the ensuing neurodegenerative process. Early and late effects of STZ were evaluated by using the reference and working memory versions of the Morris' water maze task and the evaluation of neurodegenerative markers by immunoblotting and the Fluoro-jade C histochemistry. The results revealed different types of behavioral and neurodegenerative responses, with distinct time courses. We observed an early disruption on the working memory as early as 3 h after STZ injections, which was followed by degenerative processes in the hippocampus at 1 and 15 days after STZ injections. Memory disruption increases over time and culminates with significant changes in amyloid-beta peptide and hyperphosphorylated Tau protein levels in distinct brain structures. These findings add information on the Alzheimer's disease-like STZ animal model and on the mechanisms underlying neurodegenerative processes. (C) 2012 Elsevier Inc. All rights reserved.

Effect of low-level laser therapy on pain levels in patients with temporomandibular disorders: a systematic review

Temporomandibular disorders (TMD) are characterized by the presence of temporomandibular joint (TMJ) and/or masticatory muscle pain and dysfunction. Low-level laser is presented as an adjuvant therapeutic modality for the treatment of TMD, especially when the presence of inflammatory pain is suspected. Objective: To systematically review studies that investigated the effect of low level laser therapy (LLLT) on the pain levels in individuals with TMD. Material and Methods: The databases Scopus, embase, ebsco and PubMed were reviewed from January/2003 to October/2010 with the following keywords: laser therapy, low-level laser therapy, temporomandibular joint disorders, temporomandibular joint dysfunction syndrome, temporomandibular joint, temporomandibular, facial pain and arthralgia, with the inclusion criteria for intervention studies in humans. exclusion criteria adopted were intervention studies in animals, studies that were not written in english, Spanish or Portuguese, theses, monographs, and abstracts presented in scientific events. Results: After a careful review, 14 studies fit the criteria for inclusion, of which, 12 used a placebo group. As for the protocol for laser application, the energy density used ranged from 0.9 to 105 J/cm², while the power density ranged from 9.8 to 500 mW. The number of sessions varied from 1 to 20 and the frequency of applications ranged from daily for 10 days to 1 time per week for 4 weeks. A reduction in pain levels was reported in 13 studies, with 9 of these occurring only in the experimental group, and 4 studies reporting pain relief for both the experimental group and for the placebo. Conclusion: Most papers showed that LLLT seemed to be effective in reducing pain from TMD. However, the heterogeneity of the standardization regarding the parameters of laser calls for caution in interpretation of these results. Thus, it is necessary to conduct further research in order to obtain a consensus regarding the best application protocol for pain relief in patients with TMD.

A deglutição inadequada está associada à presença de dor miofascial mastigatória?

JUSTIFICATIVA E OBJETIVOS: Os músculos da mastigação, envolvidos na fisiopatologia da dor miofascial mastigatória, também participam da função de deglutição. Diante dos resultados controversos sobre a relação entre disfunção temporomandibular (DTM) e alterações na deglutição, o objetivo deste estudo foi verificar a presença de alterações na função da deglutição em mulheres com dor miofascial mastigatória. MÉTODO: Três testes de deglutição (um sólido e dois líquidos) foram realizados em 30 mulheres com dor miofascial (grupo de estudo = GE) e 30 mulheres saudáveis (grupo controle = GC). Alterações nos padrões de deglutição como: contração da musculatura periorbicular, contração mentual, movimentos de cabeça, deglutição acompanhada de ruído, engasgos, interposição de lábio inferior, dor após deglutição e deglutição com projeção de língua para anterior foram observadas durante os três testes. Os resultados foram descritos e comparados entre os grupos através dos testes Qui-quadrado e Exato de Fisher com nível de significância de 0,05 e intervalo de confiança a 95%. RESULTADOS: Participantes do GE apresentaram chance maior de presença de atipias durante um dos testes de deglutição de líquido [teste Qui-quadrado; p < 0,05; OR: 3,29; IC 95% (1,08 - 9,95)]. Entretanto, não houve associação entre a presença de DTM e características atípicas da deglutição avaliadas em todos os testes. CONCLUSÃO: Deglutição inadequada esteve associada com a presença de dor miofascial mastigatória apenas durante a ingestão de líquido. Entretanto, não foi possível associar um tipo específico de atipia à DTM nesta amostra.

The growth of glioblastoma orthotopic xenografts in nude mice is directly correlated with impaired object recognition memory

Cognitive dysfunction is found in patients with brain tumors and there is a need to determine whether it can be replicated in an experimental model. In the present study, the object recognition (OR) paradigm was used to investigate cognitive performance in nude mice, which represent one of the most important animal models available to study human tumors in vivo. Mice with orthotopic xenografts of the human U87MG glioblastoma cell line were trained at 9, 14, and 18days (D9, D14, and D18, respectively) after implantation of 5×10(5) cells. At D9, the mice showed normal behavior when tested 90min or 24h after training and compared to control nude mice. Animals at D14 were still able to discriminate between familiar and novel objects, but exhibited a lower performance than animals at D9. Total impairment in the OR memory was observed when animals were evaluated on D18. These alterations were detected earlier than any other clinical symptoms, which were observed only 22-24days after tumor implantation. There was a significant correlation between the discrimination index (d2) and time after tumor implantation as well as between d2 and tumor volume. These data indicate that the OR task is a robust test to identify early behavior alterations caused by glioblastoma in nude mice. In addition, these results suggest that OR task can be a reliable tool to test the efficacy of new therapies against these tumors.

Exercise training prevents diastolic dysfunction induced by metabolic syndrome in rats

OBJECTIVE: High fructose consumption contributes to the incidence of metabolic syndrome and, consequently, to cardiovascular outcomes. We investigated whether exercise training prevents high fructose diet-induced metabolic and cardiac morphofunctional alterations. METHODS: Wistar rats receiving fructose overload (F) in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) for 10 weeks or kept sedentary. These rats were compared with a control group (C). Obesity was evaluated by the Lee index, and glycemia and insulin tolerance tests constituted the metabolic evaluation. Blood pressure was measured directly (Windaq, 2 kHz), and echocardiography was performed to determine left ventricular morphology and function. Statistical significance was determined by one-way ANOVA, with significance set at p<0.05. RESULTS: Fructose overload induced a metabolic syndrome state, as confirmed by insulin resistance (F: 3.6 +/- 0.2 vs. C: 4.5 +/- 0.2 mg/dl/min), hypertension (mean blood pressure, F: 118 +/- 3 vs. C: 104 +/- 4 mmHg) and obesity (F: 0.31 +/- 0.001 vs. C: 0.29 +/- 0.001 g/mm). Interestingly, fructose overload rats also exhibited diastolic dysfunction. Exercise training performed during the period of high fructose intake eliminated all of these derangements. The improvements in metabolic parameters were correlated with the maintenance of diastolic function. CONCLUSION: The role of exercise training in the prevention of metabolic and hemodynamic parameter alterations is of great importance in decreasing the cardiac morbidity and mortality related to metabolic syndrome.

Moderate/severe erectile dysfunction in patients with antiphospholipid syndrome

Purpose: To evaluate sexual function of antiphospholipid syndrome (APS) patients using the Brazilian version of the validated International Index of Erectile Function (IIEF). Materials and methods: Eleven APS male patients (Sapporo criteria) were age and race-matched with 22 healthy controls. Demographic and clinical data, drug use and antiphospholipid antibodies were evaluated. The IIEF was also self-applied. Results: Mean age (p = 0.114), frequency of Caucasian race (p = 1.00) and married status (p = 0.438) were similar in APS and controls. Mean disease duration was 8.8 +/- 4.6 years. Erectile dysfunction (ED) was frequently observed in APS versus controls (45.5 vs. 4.5%, p = 0.0096), especially moderate/severe ED (p = 0.0081). The total IIEF score (49.6 vs. 67.1, p = 0.019), erectile function (19.6 vs. 28.1, p = 0.005) and intercourse satisfaction (7.8 vs. 11.9, p = 0.009) were lower in patients than in controls. No differences were seen in orgasmic function (p = 0.114), sexual desire (p = 0.123) or overall satisfaction (p = 0.097) between the groups. The comparison between APS patients with ED (n = 5) and without ED (n = 6) revealed more arterial events in APS with ED (100 vs. 16.7%, p = 0.0152), and also longer disease duration (12 [7-16] vs. 5.5 [2-13] years, p = 0.031). A trend towards lower venous events (20 vs. 83.3%, p = 0.0801) and higher renal thrombotic microangiopathy (60% vs. 0, p = 0.0606) was observed in APS patients with ED. Demographics, clinical manifestations, smoking and antiphospholipid antibodies positivity were similar in both groups. Conclusion: To our knowledge, this was the first study that demonstrated moderate/severe ED in almost 50% of cases of a rare autoimmune disease. This alteration was linked to arterial events and longer disease duration. Lupus (2012) 21, 319-323.

The effects of 2 mg chlormadinone acetate/30 mcg ethinylestradiol, alone or combined with spironolactone, on cardiovascular risk markers in women with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder associated with metabolic dysfunction and changes in cardiovascular risk markers, and using oral contraceptives (OCs) may exert a further negative effect on these alterations in patients with PCOS. Thus, the primary objective of this study was to assess the effects on arterial function and structure of an OC containing chlormadinone acetate (2 mg) and ethinylestradiol (30 mcg), alone or combined with spironolactone (OC+SPL), in patients with PCOS. Study Design: This was a randomized, controlled clinical trial. Fifty women with PCOS between 18 and 35 years of age were randomized by a computer program to use OC or OC+SPL. Brachial artery flow-mediated vasodilation, carotid intima-media thickness and the carotid artery stiffness index were evaluated at baseline and after 6 and 12 months. Serum markers for cardiovascular disease were also analyzed. The intragroup data were analyzed using analysis of variance with Tukey's post hoc test. A multivariate linear regression model was used to analyze the intergroup data. Results: At 12 months, the increase in mean total cholesterol levels was greater in the OC+SPL group than in the OC group (27% vs. 13%, respectively; p=.02). The increase in mean sex hormone-binding globulin levels was greater in the OC group than in the OC+SPL group (424% vs. 364%, respectively; p=.01). No statistically significant differences between the groups were found for any of the other variables. Conclusion: The addition of spironolactone to an OC containing chlormadinone acetate and ethinylestradiol conferred no cardiovascular risk-marker advantages in young women with PCOS. (C) 2012 Elsevier Inc. All rights reserved.

Oral Contraceptive Containing Chlormadinone Acetate and Ethinylestradiol Reduces Plasma Concentrations of Matrix Metalloproteinase-2 in Women with Polycystic Ovary Syndrome

Biochemical markers of cardiovascular disease, including matrix metalloproteinases (MMPs), are altered in women with polycystic ovary syndrome (PCOS), with many of these alterations thought to be due to excess androgen concentrations. Despite oral contraceptives (OCs) being the first-line pharmacological treatment in women with PCOS and the importance of MMPs in many physiological conditions and pathological states, including cardiovascular diseases, no study has yet evaluated whether OCs alter plasma concentrations of MMPs. We therefore assessed whether treatment with an OC containing the anti-androgenic progestogen alters MMP profiles in women with PCOS. We analysed 20 women with PCOS who wanted hormonal contraception (OC-PCOS group), 20 ovulatory women who required hormonal contraception (OC-control group) and 20 ovulatory women who wanted non-hormonal contraception (non-OC-control group). OC consisted of cyclic use of 2 mg chlormadinone acetate/30 mu g ethinylestradiol for 6 months. Plasma concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured by gelatin zymography or enzyme-linked immunoassays. OC treatment for 6 months significantly reduced plasma MMP-2 concentrations in the OC-control and OC-PCOS groups and TIMP-2 and TIMP-1 concentrations levels in the OC-control group (all p < 0.05), but had no effects on MMP-9 concentrations or on MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in any group (all p > 0.05). These findings indicated that long-term treatment with an OC containing chlormadinone acetate plus ethinylestradiol reduced plasma MMP-2 concentrations in both healthy and PCOS women. As the latter have imbalances in circulating matrix MMPs, treatment of these women with an OC may be beneficial.

Associations among genotype, clinical phenotype, and intracellular localization of trafficking proteins in ARC syndrome

Arthrogryposisrenal dysfunctioncholestasis (ARC) syndrome is a rare autosomal recessive multisystem disorder caused by mutations in vacuolar protein sorting 33 homologue B (VPS33B) and VPS33B interacting protein, apicalbasolateral polarity regulator (VIPAR). Cardinal features of ARC include congenital joint contractures, renal tubular dysfunction, cholestasis, severe failure to thrive, ichthyosis, and a defect in platelet alpha-granule biogenesis. Most patients with ARC do not survive past the first year of life. We report two patients presenting with a mild ARC phenotype, now 5.5 and 3.5 years old. Both patients were compound heterozygotes with the novel VPS33B donor splice-site mutation c.1225+5G>C in common. Immunoblotting and complementary DNA analysis suggest expression of a shorter VPS33B transcript, and cell-based assays show that c.1225+5G>C VPS33B mutant retains some ability to interact with VIPAR (and thus partial wild-type function). This study provides the first evidence of genotypephenotype correlation in ARC and suggests that VPS33B c.1225+5G>C mutation predicts a mild ARC phenotype. We have established an interactive online database for ARC (https://grenada.lumc.nl/LOVD2/ARC) comprising all known variants in VPS33B and VIPAR. Also included in the database are 15 novel pathogenic variants in VPS33B and five in VIPAR. Hum Mutat 33:16561664, 2012. (c) 2012 Wiley Periodicals, Inc.

Primary antiphospholipid syndrome: morphofunctional penile abnormalities with normal sperm analysis

Objective: To perform a global gonadal and sexual functions assessment in primary antiphospholipid syndrome (PAPS) patients. Methods: A cross-sectional study was conducted in 12 male PAPS patients and 20 healthy controls. They were assessed by demographic data, clinical features, systematic urological examination, sexual function, testicular ultrasound, seminal parameters according to the World Health Organization (WHO), seminal sperm antibodies, and hormone profile, including follicle stimulating hormone (FSH), luteinizing hormone (LH), morning total testosterone, and thyroid hormones. Results: The median of current age and age of spermarche were similar in PAPS patients and controls (37.5 vs. 32.4 years, p = 0.270, and 13.1 vs. 12.85 years, p = 0.224, respectively), with a higher frequency of erectile dysfunction in the former group (25% vs. 0%, p = 0.044). Further analysis of PAPS patients with and without previous arterial thrombosis demonstrated that the median penis circumference was significantly lower in PAPS with arterial thrombosis than in PAPS without this complication (8.1 [6-10] vs. 10.2 [10-11] cm, p = 0.007). In addition, the median penis circumference was significantly lower in PAPS patients with erectile dysfunction than in patients without this complication (7.5 [6-9.5] vs. 9.5 [7.5-11] cm, p = 0.039). Regarding seminal analysis, the median sperm concentration, sperm motility, and normal sperm forms by WHO guidelines were comparable in PAPS patients and controls (141.5 [33-575] vs. 120.06 [34.5-329] x 106/ml, p = 0.65; 61.29 [25-80] vs. 65.42 [43-82]%, p = 0.4; 21.12 [10-42.5] vs. 23.95 [10-45]%, p = 0.45, respectively), and none of them had oligo/azoospermia. No differences were observed between PAPS patients and controls regarding the frequency of antisperm antibodies, testicular volume by ultrasound, or hormone profile (FSH, LH, morning total testosterone, and thyroid hormone) (p > 0.05). Conclusions: Normal testicular function has been identified in PAPS patients, in spite of morphofunctional penile abnormalities. Previous arterial thrombosis may underlie penile anthropometry alteration. Lupus (2012) 21, 251-256.

Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice

De Angelis K, Senador DD, Mostarda C, Irigoyen MC, Morris M. Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice. Am J Physiol Regul Integr Comp Physiol 302: R950-R957, 2012. First published February 8, 2012; doi: 10.1152/ajpregu.00450.2011.-Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 +/- 2 and F60: 118 +/- 2 mmHg) and dark periods (F15: 136 +/- 4 and F60: 136 +/- 5 mmHg) compared with controls (light: 111 +/- 2 and dark: 117 +/- 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease.

The Effects of Oxybutynin on Urinary Symptoms in Children with Williams-Beuren Syndrome

Purpose: Williams-Beuren syndrome is a genomic disorder caused by a hemizygous contiguous gene deletion on chromosome 7q11.23. Lower urinary tract symptoms are common in children with Williams-Beuren syndrome. However, there are few data on the management of voiding symptoms in this population. We report our experience using oxybutynin to treat urinary symptoms in children with Williams-Beuren syndrome. Materials and Methods: We prospectively analyzed 42 patients with Williams-Beuren syndrome and significant lower urinary tract symptoms due to detrusor overactivity diagnosed on urodynamics in a 12-week, open-label study. Urological assessment included symptomatic evaluation, the impact of lower urinary tract symptoms on quality of life, frequency-volume chart, urodynamics and urinary tract sonography. After 12 weeks of treatment with 0.6 mg/kg oxybutynin per day given in 3 daily doses, patients were assessed for treatment efficacy and side effects. Results: A total of 17 girls and 19 boys completed medical therapy and were assessed at 12 weeks. Mean +/- SD patient age was 9.2 +/- 4.3 years (range 3 to 18). The most common urinary complaint was urgency, which occurred in 31 patients (86.1%), followed by urge incontinence, which was seen in 29 (80.5%). Compared to baseline, urinary symptoms were substantially improved. The negative impact of storage symptoms on quality of life was significantly decreased from a mean +/- SD of 3.3 +/- 1.7 to 0.5 +/- 0.9 (p <0.001). Mean +/- SD maximum urinary flow improved from 14.2 +/- 15.0 to 20.5 +/- 6.4 ml per second (p <0.001). Conclusions: A total of 12 weeks of therapy with 0.6 mg/kg oxybutynin daily resulted in improvement of lower urinary tract symptoms, quality of life and maximum flow rate in most patients with Williams-Beuren syndrome.