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Bruno Schein,1,2 Gerardo Beltran,1– 3 Bárbara Regina França,1,2 Paulo RS Sanches,4 Danton P Silva Jr,4 Iraci Lucena Torres,5,6 Felipe Fegni,7 Wolnei Caumo1,2,5,8 1Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul (RS), Brazil; 2Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil; 3Institute of Neurosciences, Universidad Catolica de Cuenca, Cuenca, Ecuador; 4Laboratory of Biomedical Engineer, HCPA, Porto Alegre, RS, Brazil; 5Pain and Palliative Care Service, HCPA, Porto Alegre, RS, Brazil; 6Laboratory of Pharmacology of Pain and Neuromodulation, Experimental Research Center, HCPA, Porto Alegre, RS, Brazil; 7Laboratory of Neuromodulation and Center for Clinical Research Learning, Physics and Rehabilitation Department, Spaulding Rehabilitation Hospital, Boston, MA, USA; 8Department of Surgery, School of Medicine, UFRGS, Porto Alegre, RS, BrazilCorrespondence: Wolnei Caumo, Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre at UFRGS, Ramiro Barcelos, 2350 - CEP 90035-003 Bairro Rio Branco, Porto Alegre, RS, Brazil, Tel/Fax +55 51- 33598083, Email wcaumo@hcpa.edu.brObjective: We compare the effect of HAS, a-tDCS on the left dorsolateral prefrontal cortex (l-DLPFC), and rest-testing on pain measures [(cold pressor test (CPT) (primary outcome) and heat pain threshold]. We also compare their effects on the motor evoked potential (MEP) (primary outcome), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP).Methods: This randomized, blind, crossover trial included 18 women with fibromyalgia, aged from 18 to 65 years old. They received at random and in a crossover order a-tDCS over the l-DLPFC (2mA), HAS, or a rest-testing.Results: HAS compared to a-tDCS increased the pain tolerance with a moderate effect size (ES) [Cohen’s f=− 0.78; (CI 95%; − 1.48 to − 0.12)]. While compared to rest-testing, HAS increased the CPT with a large ES [Cohen’s f=− 0.87; (CI 95%; − 1.84 to − 0.09)]. The a-tDCS compared to HAS increased the MEP amplitude with large ES [Cohen’s f=− 1.73 (CI 95%; − 2.17 to − 0.17)]. Likewise, its ES compared to rest-testing in the MEP size was large [Cohen’s f=− 1.03; (CI 95%; − 2.06 to − 0.08)].Conclusion: These findings revealed that HAS affects contra-regulating mechanisms involved in perception and pain tolerance, while the a-tDCS increased the excitability of the corticospinal pathways. They give a subsidy to investigate their effect as approaches to counter regulate the maladaptive neuroplasticity involved in fibromyalgia.Clinical Trial Registration: www.ClinicalTrials.gov, identifier – NCT05066568.Keywords: tDCS, hypnosis, hypnotic analgesia, chronic pain, fibromyalgia, pain threshold, cold pressor test, CPM-test

Although fibromyalgia is a widespread chronic pain condition where 90 percent of patients are women, they are underrepresented in Randomized Clinical Trials (RCTs). We aim to describe the willingness to participate, assess different factors, and explore the impact of sociodemographic and clinical characteristics on perceived barriers to trial participation. This is a cross-sectional survey targeting women with fibromyalgia. Univariate and multivariate logistic regression were performed. Of the 436 women with fibromyalgia, 56 percent were very likely to participate in RCTs. Minorities expressed less interest than non-minorities, while higher pain scores, previous participation, and younger patients reported a higher interest. Barriers significantly associated with a reduced willingness were: the participant's perception (side effects, distance, potential negative impact), the center (reputation), the trial protocol (number of visits, placebo), and trial awareness by their physician. In a multivariate analysis, older age, low education, lower income, and higher pain scores were associated with perceived barriers to RCT participation. Despite the high interest to participate, factors such as side effects, the center's distance, number of visits, placebo treatments, and the institution's reputation must be considered in clinical trials for women with fibromyalgia. [ABSTRACT FROM AUTHOR]

Gerardo Beltran Serrano,1– 3 Laura Pooch Rodrigues,2 Bruno Schein,1,2 Maxciel Zortea,1,2 Iraci Lucenada Silva Torres,1,4,5 Felipe Fregni,6 Wolnei Caumo1,2,5 1Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal Do Rio Grande Do Sul (UFRGS), Porto Alegre, Brazil; 2Laboratory of Pain and Neuromodulation at Hospital De Clínicas De Porto Alegre (HCPA), Porto Alegre, Brazil; 3Psychology Department, Universidad Catolica De Cuenca, UCACUE, Cuenca, Ecuador; 4Department of Pharmacology, Institute of Health Sciences (ICBS), Universidade Federal Do Rio Grande Do Sul (UFRGS), Porto Alegre, Brazil; 5Pharmacology of Pain and Neuromodulation: Pre-Clinical Investigations Research Group, Universidade Federal Do Rio Grande Do Sul (UFRGS), Porto Alegre, Brazil; 6Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USACorrespondence: Wolnei Caumo Fax + (55) 51- 3359.8083Email wcaumo@hcpa.edu.brObjective: We evaluated whether active(a)-tDCS combined with hypnotic analgesia suggestion (HS) would be more effective than a single active(a)-tDCS, and/or sham-(s)-tDCS and s-tDCS/HS on the following outcomes: function of descending pain modulatory system (DPMS) during the conditioned pain modulation test (CPM-test) (primary outcome), heat pain threshold (HPT), heat pain tolerance (HPTo) and cold pressor test (CPT) (secondary outcomes). We also examined whether their effects are related to neuroplasticity state evaluated by serum brain-derived-neurotropic factor (BDNF).Materials and Methods: Forty-eight females received one session of one of the four interventions (a-tDCS/HS, s-tDCS/HS, a-tDCS, and s-tDCS) in an incomplete randomized crossover sequence. The a-tDCS or s-tDCS was applied over the left dorsolateral prefrontal cortex (DLPFC) for 30 minutes at 2mA.Results: A generalized linear model revealed a significant main effect for the intervention group (P < 0.032). The delta-(Δ) pain score on the Numerical Pain Scale (NPS0-10) during CPM-test in the a-tDCS/HS group was − 0.25 (0.43). The (Δ) pain score on NPS (0– 10) during CPM-test in the other three groups was a-tDCS=− 0.54 (0.41), HS − 0.01 (0.41) and s-tDCS/HS=− 0.19 (0.43). A-tDCS/HS intervention increased the CPT substantially compared to all other interventions. Also, higher baseline levels of BDNF were associated with a larger change in CPT and HPTo.Conclusion: These findings indicate that the HS combined with a-tDCS mitigated the effect of the a-tDCS on the DPMS. The a-tDCS up-regulates the inhibition on DPMS, and the HS improved pain tolerance. And, together they enhanced the reaction time substantially upon the CPT.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03744897.Keywords: tDCS, hypnotic analgesia, conditioned pain modulation, pain perception

Dirson João Stein, 1, 2,* Liciane Fernandes Medeiros, 1, 3, 4,* Wolnei Caumo, 2 Iraci LS Torres 1– 3 1Laboratório de Farmacologia da Dor e Neuromodulação, Investigações Pré-Clínicas, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil; 2Programa de Pós-Graduação em Medicina: Ciências Médicas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; 3Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, UFRGS, Porto Alegre, RS, Brazil; 4Programa de Pós-Graduação em Saúde e Desenvolvimento Humano, Universidade La Salle, Canoas, RS, Brazil*These authors contributed equally to this workCorrespondence: Iraci LS TorresPharmacology Department, ICBS, UFRGS, Rua Sarmento Leite, 500 - Sala 237, 90.050-170, Porto Alegre, RS, BrazilTel +55 51 3308 3183Fax +55 51 3308 3121Email iltorres@hcpa.edu.brAbstract: Anxiety is one of the most prevalent and debilitating psychiatric conditions worldwide. Pharmaco- and psycho-therapies have been employed in the treatment of human anxiety to date. Yet, either alone or in combination, unsatisfactory patient outcomes are prevalent, resulting in a considerable number of people whose symptoms fail to respond to conventional therapies with symptoms remaining after intervention. The demand for new therapies has given birth to several noninvasive brain stimulation techniques. Transcranial direct current stimulation (tDCS) has arisen as a promising tool and has been proven to be safe and well tolerated for the treatment of many diseases, including chronic pain, depression, and anxiety. Here, reports of the use of tDCS in anxiety disorders in human patients were reviewed and summarized. A literature search was conducted in mid-2019, to identify clinical studies that evaluated the use of tDCS for the treatment of anxiety behavior. The PubMed, Web of Science, and Scielo and PsycInfo databases were explored using the following descriptors: “anxiety”, “anxious behavior”, “tDCS”, and “transcranial direct current stimulation”. Among the selected articles, considerable variability in the type of tDCS treatment applied in interventions was observed. Evidence shows that tDCS may be more effective when used in combination with drugs and cognitive behavioral therapies; however future large-scale clinical trials are recommended to better clarify the real effects of this intervention alone, or in combination with others.Keywords: transcranial electrical stimulation, psychiatric disorder, anxious behavior, humans, clinical research

José Ary Berniger Romariz,1,2 Cássio Nonnemacher,2 Mylena Abreu,2 Joice Dickel Segabinazi,2 Janete Shatkoski Bandeira,2 Gerardo Beltran,1–3 Andressa Souza,4 Iraci LS Torres,5 Wolnei Caumo1,2,6–81Postgraduate Program in Medical Sciences, Faculdade de Medicina,Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 2Laboratory of Pain and Neuromodulation, Hospital de Clinicas de Porto Alegre, Brazil; 3Psychology Department, Cuenca Catholic University, Cuenca, Ecuador; 4Postgraduate Program in Health and Human Development, La Salle Universitary Center, Canoas, Brazil; 5Pharmacology Department, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 6Pain and Anesthesia,Surgery Department, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 7Pain and Palliative Care Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; 8Laboratory of Pain and Neuromodulation, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilObjectives: The primary aim was to assess the psychometric properties (including internal consistency, construct validity, criterion validity, criterion-group validity and responsiveness) of the Fear of Pain Questionnaire (FOPQ) for adolescents (FOPQ-A) and parents (FOPQ-P) translated to Brazilian Portuguese (BrP). The secondary aim was to analyze the factor structures and their ability to identify subjects with chronic pain conditions and identify the relationship of the BrP FOPQ-A with saliva brain-derived neurotrophic-factor (BDNF).Methods: A cross-sectional study was conducted with 286 adolescents aged 11 to 18 (257 healthy adolescents [157 females] and 29 adolescents with chronic pain [16 females]). Parents and adolescents completed the BrP-FOPQ. A team of experts translated the FOPQ according to international guidelines. Convergent validity and factor analysis were performed. Later, a subsample (n=146) was used to correlate the BrP-FOPQ-A with saliva BDNF.Results: The BrP-FOPQ for adolescents and parents presented strong psychometric properties (Cronbach’s α equal to 0.92 and 0.91, respectively). BrP-FOPQ-A confirmatory factor analysis yielded a two-factor structure while the factorial analyses of BrP-FOPQ-P demonstrated that the best solution was a three-structure factorial. The BrP-FOPQ-P scores in healthy adolescents and those in chronic pain conditions was 34.13 (16.71) vs 43.14 (18.08), respectively. A generalized mixed model demonstrated that the scores in the BrP-FOPQ-A are higher in those with chronic pain conditions compared to healthy subjects (29.20 [12.77] vs 33.80 [10.76], respectively; Wald χ2= 17.80; df=1, P

Maria da Graca-Tarragó,1,2 Mateus Lech,2 Letícia Dal Moro Angoleri,2 Daniela Silva Santos,2 Alícia Deitos,1,2 Aline Patrícia Brietzke,1,2 Iraci LS Torres,1,3 Felipe Fregni,4 Wolnei Caumo1,2,5,6 1Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 2Laboratory of Pain and Neuromodulation, HCPA, Porto Alegre, Brazil; 3Pharmacology Department, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 4Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA; 5Surgery Department, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 6Pain and Palliative Care Service, HCPA, Porto Alegre, Brazil Background: Neuroplastic changes in nociceptive pathways contribute to severity of symptoms in knee osteoarthritis (KOA). A new look at neuroplastic changes management includes modulation of the primary motor cortex by transcranial direct current stimulation (tDCS). Objectives: We investigated whether tDCS combined with intramuscular electrical stimulation (EIMS) would be more efficacious than a sham (s) intervention (s-tDCS/s-EIMS) or a single active(a)-tDCS/s-EIMS intervention and/or s-tDCS/a-EIMS in the following domains: pain measures (visual analog scale [VAS] score and descending pain modulatory system [DPMS], and outcomes, and analgesic use, disability, and pain pressure threshold (PPT) for secondary outcomes. Registration: The trial is registered in Clinical trials.gov: NCT01747070. Methods: Sixty women with KOA, aged 50–75 years old, randomly received five sessions of one of the four interventions (a-tDCS/a-EIMS, s-tDCS/s-EIMS, a-tDCS/s-EIMS, and s-tDCS/a-EIMS). tDCS was applied over the primary motor cortex (M1), for 30 minutes at 2 mA and the EIMS paraspinal of L1–S2. Results: A generalized estimating equation model revealed the main effect of the a-tDCS/a-EIMS in the VAS pain scores at end treatment compared with the other three groups (P

Wolnei Caumo,1–3 Maria Paz Hidalgo,4,5 Andressa Souza,6 Iraci LS Torres,1,7 Luciana C Antunes8 1School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; 2Pain and Palliative Care Service at Hospital de Clínicas de Porto Alegre (HCPA), Laboratory of Pain and Neuromodulation at UFRGS, Porto Alegre, Brazil; 3Pain and Anesthesia in Surgery Department, School of Medicine, UFRGS, Porto Alegre, Brazil; 4Psychiatry Department, School of Medicine, UFRGS, Porto Alegre, Brazil; 5Laboratorio de Cronobiologia e Sono do Hospital de Clinicas de Porto Alegre; Porto Alegre, Brazil; 6Postgraduate Program in Health and Human Development, La Salle Universitary Center, Canoas, Brazil; 7Pharmacology Department, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, Brazil; 8Centro de Ciências da Saúde – Departamento de Nutrição da Universidade Federal De Santa Catarina, Florianopolis, Brazil Objective: This study compared urinary 6-sulfatoxymelatonin (aMT6s) over 24 hours among fibromyalgia (FM), major depression disorder (MDD), and healthy control (HC) groups, and examined whether rhythm is correlated with depressive symptoms. To answer this question we compared the rhythm of urinary aMT6s secretion among each group in four time series: morning (06:00–12:00 hours), afternoon (12:00–18:00 hours), evening (18:00–24:00 hours), and night (24:00–06:00 hours). In the FM subjects, we assessed if the rhythm of urinary aMT6s secretion is associated with pain severity, sleep quality, number of trigger points (NTPs), and the pain pressure threshold (PPT). Patients and methods: We included 54 women, aged 18–60 years with diagnosis of FM (n=18), MDD (n=19), and HC (n =17). The 24-hour urinary aMT6s was evaluated according to four standardized periods. The assessment instruments were the Hamilton Depression Rating Scale (HDRS), Pittsburgh Sleep Quality Index, and Fibromyalgia Impact Questionnaire. Results: A generalized estimating equation revealed no difference in the daily load of aMT6s secretion among the three groups (P=0.49). However, at the daily time (06:00–18:00 hours), the load secretion of aMT6s reached 41.54% and 60.71% in the FM and MDD, respectively, as compared to 20.73% in the HC (P

Wolnei Caumo,1–4 Luciana C Antunes,1 Jéssica Lorenzzi Elkfury,1 Evelyn G Herbstrith,5 Raquel Busanello Sipmann,6 Andressa Souza,7 Iraci LS Torres,1,8 Vinicius Souza dos Santos,1 Randy Neblett9 1Postgraduate Program in Medical Sciences, School of Medicine, 2Pain and Palliative Care Service, Hospital de Clínicas de Porto Alegre, 3Laboratory of Pain and Neuromodulation, 4Surgery Department, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, 5School of Psychology, Pontifícia Universidade Católica do Rio Grande do Sul, 6School of Medicine, Universidade Federal do Rio Grande do Sul, 7Postgraduate Program in Health and Human Development, La Salle University Center, Canoas, 8Pharmacology Department, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 9PRIDE Research Foundation, Dallas, TX, USA Objectives: The primary aim was to assess the psychometric properties (including internal consistency, construct validity, reproducibility, and factor structure) of the Central Sensitization Inventory (CSI), adapted and validated for a Brazilian population (CSI-BP). Additionally, we evaluated the relationship between the CSI-BP and the serum brain-derived neurotrophic factor (BDNF) and determined if the symptoms elicited by the CSI-BP discriminate between subjects who do/do not respond to the conditioned pain modulation (CPM) task, as assessed by change in numeric pain scale (0–10) score. Patients and methods: A cross-sectional study was conducted in a pain clinic in a tertiary teaching hospital. A total of 222 adults with chronic musculoskeletal pain and 63 healthy control subjects completed the CSI-BP and the Brazilian Portuguese pain-catastrophizing scale (BP-PCS). A team of experts translated the CSI according to the international guidelines. Test–retest, item analysis, convergent validity, and factor analysis were performed. Later, a random subsample (n=77) was used to correlate the CSI-BP adjusted index with change in numeric pain-scale score during the CPM task and a BDNF blood sample. Results: The CSI-BP presented strong psychometric properties (test–retest reliability 0.91, Cronbach’s a=0.91). Confirmatory factor analysis yielded a four-factor structure, supporting the original English version. The CSI-BP adjusted index showed moderate positive correlation with the BP-PCS, and classified more than 80% of patients correctly vs healthy controls. Serum BDNF levels explained 27% of the variation in the CSI-BP adjusted index. Subjects with impairment in the descending modulatory system had higher CSI-BP adjusted index scores than subjects who responded normally to the CPM task: 49.35 (12.1) vs 39.5 (12.33), respectively (P

Joanna Ripoll Rozisky,1,2,4,* Yasmine Nonose,1,4,* Gabriela Laste,1,2,4 Vinicius Souza dos Santos,1,4 Isabel Cristina de Macedo,1,2,4 Ana Maria Oliveira Battastini,2,3 Wolnei Caumo,2,4 Iraci LS Torres1,2,41Laboratório de Farmacologia da Dor e Neuromodulação: Modelos Animais, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, 2Programa de Pós-Graduação em Medicina, Ciências Médicas, 3Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil; 4Unidade de Experimentação Animal e Grupo de Pesquisa e Pós-Graduação, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil *Both authors contributed equally to this workAbstract: Morphine has been widely used in neonatal pain management. However, this treatment may produce adaptive changes in several physiologic systems. Our laboratory has demonstrated that morphine treatment in neonate rats alters nucleoside triphosphate diphosphohydrolase (NTPDase) activity and gene expression in central nervous system structures. Considering the relationship between the opioid and purinergic systems, our aim was to verify whether treatment with morphine from postnatal days 8 (P8) through 14 (P14) at a dose of 5 µg per day alters NTPDase and 5´-nucleotidase activities in rat serum over the short, medium, and long terms. After the in vivo assay, the morphine group showed increased hydrolysis of all nucleotides at P30, and a decrease in adenosine 5´-diphosphate hydrolysis at P60. Moreover, we found that nucleotidase activities change with age; adenosine 5´-triphosphate hydrolysis activity was lower at P16, and adenosine 5'-monophosphate hydrolysis activity was higher at P60. These changes are very important because these enzymes are the main regulators of blood nucleotide levels and, consequently, nucleotide signaling. Our findings showed that in vivo morphine treatment alters nucleotide hydrolysis in rat blood serum, suggesting that purine homeostasis can be influenced by opioid treatment during the neonatal period.Keywords: 5´-nucleotidase, morphine, neonate, NTPDase, rat blood serum

Gabriela Laste,1–3 Isabel Cristina de Macedo,1,3 Joanna Ripoll Rozisky,1–3 Fernanda Ribeiro da Silva,1,3 Wolnei Caumo,1,2 Iraci LS Torres1–31Laboratório de Farmacologia da Dor, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, 2Programa de Pós-Graduação em Medicina, Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 3Unidade de Experimentação Animal e Grupo de Pesquisa e Pós-Graduação, Hospital de Clínicas de Porto Alegre, Porto Alegre, BrazilAbstract: In view of the broad range of effects attributed to melatonin, this study evaluated its analgesic effect on inflammatory pain induced by complete Freund's adjuvant (CFA) in Wistar rats. Inflammation was induced by intradermal CFA injection in the hind paw of all animals, which were then divided into two groups that received either 60 mg/kg of melatonin or vehicle (1% alcohol in saline), intraperitoneally, for three days. The analgesic effect of melatonin was assessed by the hot-plate test, immediately and thereafter at 30, 60, 90, and 120 minutes after the first administration and 24 hours after once-daily administration for 2 more days. After CFA injection, melatonin administration increased withdrawal latency at 60 minutes after the first dose. After the end of treatment, melatonin showed a significant analgesic effect on inflammatory pain. This study paves the way for exploration of how brief courses of treatment could improve this analgesic effect in the late phases of inflammatory pain.Keywords: analgesic response, complete Freund's adjuvant, hot-plate test, inflammation, melatonin, nociception

Summary: Mortality and morbidity for high‐risk surgical patients are often high, especially in low‐resource settings. Enhanced peri‐operative care has the potential to reduce preventable deaths but must be designed to meet local needs. This before‐and‐after cohort study aimed to assess the effectiveness of a postoperative 48‐hour enhanced care pathway for high‐risk surgical patients ('high‐risk surgical bundle') who did not meet the criteria for elective admission to intensive care. The pathway comprised of six elements: risk identification and communication; adoption of a high‐risk post‐anaesthesia care unit discharge checklist; prompt nursing admission to ward; intensification of vital signs monitoring; troponin measurement; and prompt access to medical support if required. The primary outcome was in‐hospital mortality. Data describing 1189 patients from two groups, before and after implementation of the pathway, were compared. The usual care group comprised a retrospective cohort of high‐risk surgical patients between September 2015 and December 2016. The intervention group prospectively included high‐risk surgical patients from February 2019 to March 2020. Unadjusted mortality rate was 10.5% (78/746) for the usual care and 6.3% (28/443) for the intervention group. After adjustment, the intervention effect remained significant (RR 0.46 (95%CI 0.30–0.72). The high‐risk surgical bundle group received more rapid response team calls (24% vs. 12.6%; RR 0.63 [95%CI 0.49–0.80]) and surgical re‐interventions (18.9 vs. 7.5%; RR 0.41 [95%CI 0.30–0.59]). These data suggest that a clinical pathway based on enhanced surveillance for high‐risk surgical patients in a resource‐constrained setting could reduce in‐hospital mortality. [ABSTRACT FROM AUTHOR]

Background: Preoperative stress might influence postoperative pain, thereby, it is desirable to assess it more precisely. Thus, we developed and evaluated the psychometric properties of a brief measure of emotional preoperative stress (B-MEPS) index using Item Response Category Characteristic Curves. We validated and assessed whether the B-MEPS can predict moderate to intense acute postoperative pain (MIAPP).Methods: We included 863 adult patients who underwent elective surgeries (ASA I-III physical status). The B-MEPS was constructed based on items selected from instruments to assess anxiety, depression, future self-perception and minor psychiatric disorders. We identified 24 items with greatest discriminant power to identify patients who should undergo surgery to treat cancer with MIAPP. The reliability was maximized using the Cronbach's alpha indices. Fifteen items remained, which were adjusted by the Generalized Partial Credit Model. The convergent validity was assessed correlating the B-MEPS index with the pain catastrophizing (n = 100). Finally, the B-MEPS was applied in a prospective cohort of patients who underwent an abdominal hysterectomy (n = 150).Results: The Cronbach's alpha for selected items was 0.83. The correlation coefficient between B-MEPS index and catastrophizing was r = 0.37 (P < 0.01). A hierarchical regression model evidenced that the B-MEPS index was a factor independent to predict MIAPP after an abdominal hysterectomy [odds ratio (OR)=1.20, confidence interval (CI) 95% 1.05-1.43).Conclusions: The B-MEPS index presents satisfactory psychometric evaluations based on its internal consistency, convergent, and discriminant validity. The B-MEPS is a propensity index to MIAPP, which might help the clinician to decide on the best therapeutic approaches for acute postoperative pain. [ABSTRACT FROM AUTHOR]

Background Chronic stress (CS) is associated with a decrease in pain threshold caused by the changes in neural pain circuits. It can be associated to glucocorticoid imbalance with alterations in neural circuitry. Inhibition of stress-induced pain-related neural changes by using techniques that safely induce neuroplasticity such as transcranial direct current stimulation (tDCS) may prevent hyperalgesia triggered by CS. Objective This study aimed to verify the effect of tDCS performed prior to CS exposure on nociceptive response. Methods Thirty-two rats were distributed in the following groups: control; stress; sham-tDCS + stress; and tDCS + stress. Bicephalic active tDCS was performed for 8 consecutive days before the CS exposure. The pain threshold was evaluated using a hot plate and tail flick latency (TFL) tests. Results The tDCS exposure increased the pain threshold on stressed rats. Conclusion The data obtained indicate that the treatment with bicephalic active tDCS before chronic stress exposure prevents stress-induced hyperalgesia. [ABSTRACT FROM AUTHOR]

Background: Pain is a sensory and emotional experience that is influenced by physiologic, sensory, affective, cognitive, socio-cultural, and behavioral factors. Consistent with the perspective to improve the postoperative pain control, the present study has the purpose of assessing the effect of presurgical clinical factors, psychological and demographic characteristics as predictors for reporting moderate to intense acute postoperative pain.Methods: A prospective cohort study was performed with 346 inpatients undergoing abdominal elective surgery (ASA physical status I-III, age range 18-60 years). The measuring instruments were Pain Visual Analog Scale, the State-Trait Anxiety Inventory, and the Montgomery-Asberg Depression Rating Scale. Multivariate conditional regression modeling was used to determine independent predictors for moderate to intense acute postoperative pain.Results: Moderate to intense acute postoperative pain was associated with status ASA III (odds ratio (OR) = 1.99), age (OR = 4.72), preoperative moderate to intense pain (OR = 2.96), chronic pain (OR = 1.75), high trait-anxiety and depressive mood moderate to intense (OR = 1.74 and OR = 2.00, respectively). Patients undergoing surgery to treat cancer presented lower risk for reporting moderate to intense pain OR = 0.39, as well as those that received the epidural analgesia and multimodal analgesia with systemic opioid (OR = 0.09 and OR = 0.16, respectively).Conclusions: The identification of predictive factors for intense acute postoperative pain may be useful for designing specific preventive interventions to relieve patient suffering. Especially because few of these variables are accessible for medical intervention, which would improve the clinical outcomes and quality of life of patients at risk of moderate to intense acute postoperative pain. [ABSTRACT FROM AUTHOR]

Background: Anxiety is defined as a set of behavioural manifestations that can be divided into state- and trait-anxiety. State-anxiety is a transitory emotional condition that varies in intensity and fluctuates over time. Trait-anxiety is a personality trait which remains relatively stable over time. The objective of this study was to identify and quantify perioperative risk factors for immediate postoperative anxiety in children.Methods: A prospective cohort study was performed with 90 schoolchildren, ages ranging from 7 to 13 years old, ASA physical status I-II, submitted to elective surgery. The measuring instruments were verbal scale of pain, visual analogue scale (VAS), Trait-State Anxiety Inventory for Children (STAIC), Trait-State Anxiety Inventory (STAI) for parents, and structured questionnaire.Results: Patients not submitted to analgesic block and patients with moderate and intense pain presented an estimated risk 5- and 13-fold greater for high levels of postoperative state-anxiety, respectively. High levels of preoperative state-anxiety and administration of doses of midazolam less than 0.056 mg x kg(-1) constituted an estimated risk for postoperative state-anxiety of 3- and 4-fold, respectively. A positive history of previous surgery was associated with lower risk for postoperative anxiety.Conclusions: High levels of preoperative state-anxiety, administration of less than 0.056 mg x kg(-1) of midazolam, absence of analgesic block and presence of moderate and intense postoperative pain constituted risk factors for immediate postoperative state-anxiety in children. Previous surgery reduced the risk for postoperative anxiety. [ABSTRACT FROM AUTHOR]

The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. Therefore, a group of research and clinician experts on tDCS were convened to review the research and clinical use of tDCS. This report reviews the regulatory status of tDCS and summarizes the results according to research, off-label, and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan, and the US. Research use, off label treatment, and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials. [ABSTRACT FROM AUTHOR]