Comparação entre a recuperação da economia de corrida e força muscular medida por diferentes métodos após o dano muscular

The goal of the present study was to investigate possible differences towards strenght recovery measured by different methods and running economy (RE), after one session of downhill running (DR), in order to induce muscle damage (MD). Our hypothesis is that the strenght recovery measured by jumps is more alike RE markers, due to the measures' specificity. Ten male subjects, ages 18 to 30, apparently healthy, without any experience with strenght training at least 6 months before the tests took place in this study. After going to the lab twice (to familiarize themselves with the protocols, and determine their maximum oxygen consumption/running speeds), they went to the lab five times in the following week, in order to collect all the variables before, immediately after, and 24, 48, 72 and 96 hours in. The variables obtained were: stride frequency (SF), stride lenght (SL), oxygen volume (VO2), carbon dioxide volume (VCO2), ventilation (VE), lactate blood concentration ([Lac]), isometric peak torque (IPT), subjective pain perception (SPP), effort perception (EP), medial-portion circumference (CIR), knee movement extent (EXT), torque development rate (TDR), counter movement jump and squat jump height (HCM and HS), strenght development rate of both jumps (SDCM and SDS), and maximum soil strenght reaction (SRCM and SRS). Changes over time in all variables were verified by one way variancy analysis. Differences between the strenght measures were verified by two way variancy analysis. When significant effects were verified, Tuckey's post-hoc were applied. The significancy level taken on this study was p < 0,05. Of all indirect muscle damage markers, IPT, SPP and TDR were the only ones in which ocurred significant changes. We couldn't find the moments where this happened for TDR with the post-hoc used. On RE markers, VO2, [Lac] and VE suffered significant effects over time. About the jumps variables, only SDCM and HCM presented significant...

Influência do método de avaliação no diagnóstico da dor muscular de início tardio após corrida em declive

Several methods are used towards delayed onset muscle soreness appraisal. This study's goal was to investigate, amongst three commonly adopted methods, which one would be the most effective (the one that shows higher values) in the quantification of this phenomenon. 10 male subjects, of age 22.8 ± 3.1 years old, weight 80 ± 12.4 kg, height 174 ± 0.07 cm, without recent experience with strength training (lower limbs) and/or running took place in this study. All subjects carried out a muscle damage induction protocol, which consisted of 30 minute downhill running (-16% or -9.09º) at 80% speed compared to their maximum oxygen consumption. Muscle damage determinants such as isometric peak torque, knee joint range of motion and circumference of the medial portion of the thight were measured before, during, 24, 48, 72 and 96 hours after downhill running. The subjective pain perception was measured simultaneously with the other determinants through three different tests: sitting on and getting up of a chair; climbing and descending from a 45cm step; and self thigh palpation. After going through all subjective pain perception tests, the subjects filled out a visual analog scale with their perception of pain. Muscle damage changes over time were compared through variance analysis (ANOVA) one way for repeated measures. Subjective pain perception values obtained in all three different tests were compared through two way ANOVAs for repeated numbers. The significance level adopted in this study was z ≤ 0.05. The results showed that the step test was the on which better evaluated the delayed onset muscle soreness. No significant differences were found through the ADM and CIR recovery markers. Downhil running determined reduced of PTI (~22.4%). Significant links between pain were obtained for both subjective pain perception tests starting at 24 and 48 hours, where the highest registered average happened in the step test after 48h, with high...

Determinants of discordance in patients' and physicians' rating of rheumatoid arthritis disease activity

Objective To assess the determinants of patients' (PTGL) and physicians' (MDGL) global assessment of rheumatoid arthritis (RA) activity and factors associated with discordance among them. Methods. A total of 7,028 patients in the Quantitative Standard Monitoring of Patients with RA study had PTGL and MDGL assessed at the same clinic visit on a 0-10-cm visual analog scale (VAS). Three patient groups were defined: concordant rating group (PTGL and MDGL within >= 2 cm), higher patient rating group (PTGL exceeding MDGL by > 2 cm), and lower patient rating group (PTGL less than MDGL by > 2 cm). Multivariable regression analysis was used to identify determinants of PTGL and MDGL and their discordance. Results. The mean +/- SD VAS scores for PTGL and MDGL were 4.01 +/- 2.70 and 2.91 +/- 2.37, respectively. Pain was overwhelmingly the single most important determinant of PTGL, followed by fatigue. In contrast, MDGL was most influenced by swollen joint count (SJC), followed by erythrocyte sedimentation rate (ESR) and tender joint count (TJC). A total of 4,454 (63.4%), 2,106 (30%), and 468 (6.6%) patients were in the concordant, higher, and lower patient rating groups, respectively. Odds of higher patient rating increased with higher pain, fatigue, psychological distress, age, and morning stiffness, and decreased with higher SJC, TJC, and ESR. Lower patient rating odds increased with higher SJC, TJC, and ESR, and decreased with lower fatigue levels. Conclusion. Nearly 36% of patients had discordance in RA activity assessment from their physicians. Sensitivity to the "disease experience" of patients, particularly pain and fatigue, is warranted for effective care of RA.

Visual-somatosensory interactions in mental representations of the body and the face

The body is represented in the brain at levels that incorporate multisensory information. This thesis focused on interactions between vision and cutaneous sensations (i.e., touch and pain). Experiment 1 revealed that there are partially dissociable pathways for visual enhancement of touch (VET) depending upon whether one sees one’s own body or the body of another person. This indicates that VET, a seeming low-level effect on spatial tactile acuity, is actually sensitive to body identity. Experiments 2-4 explored the effect of viewing one’s own body on pain perception. They demonstrated that viewing the body biases pain intensity judgments irrespective of actual stimulus intensity, and, more importantly, reduces the discriminative capacities of the nociceptive pathway encoding noxious stimulus intensity. The latter effect only occurs if the pain-inducing event itself is not visible, suggesting that viewing the body alone and viewing a stimulus event on the body have distinct effects on cutaneous sensations. Experiment 5 replicated an enhancement of visual remapping of touch (VRT) when viewing fearful human faces being touched, and further demonstrated that VRT does not occur for observed touch on non-human faces, even fearful ones. This suggests that the facial expressions of non-human animals may not be simulated within the somatosensory system of the human observer in the same way that the facial expressions of other humans are. Finally, Experiment 6 examined the enfacement illusion, in which synchronous visuo-tactile inputs cause another’s face to be assimilated into the mental self-face representation. The strength of enfacement was not affected by the other’s facial expression, supporting an asymmetric relationship between processing of facial identity and facial expressions. Together, these studies indicate that multisensory representations of the body in the brain link low-level perceptual processes with the perception of emotional cues and body/face identity, and interact in complex ways depending upon contextual factors.

Pharmacogenomic considerations in opioid analgesia

Translating pharmacogenetics to clinical practice has been particularly challenging in the context of pain, due to the complexity of this multifaceted phenotype and the overall subjective nature of pain perception and response to analgesia. Overall, numerous genes involved with the pharmacokinetics and dynamics of opioids response are candidate genes in the context of opioid analgesia. The clinical relevance of CYP2D6 genotyping to predict analgesic outcomes is still relatively unknown; the two extremes in CYP2D6 genotype (ultrarapid and poor metabolism) seem to predict pain response and/or adverse effects. Overall, the level of evidence linking genetic variability (CYP2D6 and CYP3A4) to oxycodone response and phenotype (altered biotransformation of oxycodone into oxymorphone and overall clearance of oxycodone and oxymorphone) is strong; however, there has been no randomized clinical trial on the benefits of genetic testing prior to oxycodone therapy. On the other hand, predicting the analgesic response to morphine based on pharmacogenetic testing is more complex; though there was hope that simple genetic testing would allow tailoring morphine doses to provide optimal analgesia, this is unlikely to occur. A variety of polymorphisms clearly influence pain perception and behavior in response to pain. However, the response to analgesics also differs depending on the pain modality and the potential for repeated noxious stimuli, the opioid prescribed, and even its route of administration.

Neural correlates of antinociception in borderline personality disorder

CONTEXT: A characteristic feature of borderline personality disorder (BPD) is self-injurious behavior in conjunction with stress-induced reduction of pain perception. Reduced pain sensitivity has been experimentally confirmed in patients with BPD, but the neural correlates of antinociceptive mechanisms in BPD are unknown. We predicted that heat stimuli in patients with BPD would activate brain areas concerned with cognitive and emotional evaluation of pain. OBJECTIVE: To assess the psychophysical properties and neural correlates of altered pain processing in patients with BPD. DESIGN: Case-control study. SETTING: A university hospital. PARTICIPANTS: Twelve women with BPD and self-injurious behavior and 12 age-matched control subjects. INTERVENTIONS: Psychophysical assessment and blood oxygen level-dependent functional magnetic resonance imaging during heat stimulation with fixed-temperature heat stimuli and individual-temperature stimuli adjusted for equal subjective pain in all the participants. MAIN OUTCOME MEASURE: Blood oxygen level-dependent functional magnetic resonance imaging signal changes during heat pain stimulation. RESULTS: Patients with BPD had higher pain thresholds and smaller overall volumes of activity than controls in response to identical heat stimuli. When the stimulus temperature was individually adjusted for equal subjective pain level, overall volumes of activity were similar, although regional patterns differed significantly. Patient response was greater in the dorsolateral prefrontal cortex and smaller in the posterior parietal cortex. Pain also produced neural deactivation in the perigenual anterior cingulate gyrus and the amygdala in patients with BPD. CONCLUSION: The interaction between increased pain-induced response in the dorsolateral prefrontal cortex and deactivation in the anterior cingulate and the amygdala is associated with an antinociceptive mechanism in patients with BPD.

The effect of naloxone-3-glucuronide on colonic transit time in healthy men after acute morphine administration: a placebo-controlled double-blinded crossover preclinical volunteer study

BACKGROUND: Constipation is a significant side effect of opioid therapy. We have previously demonstrated that naloxone-3-glucuronide (NX3G) antagonizes the motility-lowering-effect of morphine in the rat colon. AIM: To find out whether oral NX3G is able to reduce the morphine-induced delay in colonic transit time (CTT) without being absorbed and influencing the analgesic effect. METHODS: Fifteen male volunteers were included. Pharmacokinetics: after oral administration of 0.16 mg/kg NX3G, blood samples were collected over a 6-h period. Pharmacodynamics: NX3G or placebo was then given at the start time and every 4 h thereafter. Morphine (0.05 mg/kg) or placebo was injected s.c. 2 h after starting and thereafter every 6 h for 24 h. CTT was measured over a 48-h period by scintigraphy. Pressure pain threshold tests were performed. RESULTS: Neither NX3G nor naloxone was detected in the venous blood. The slowest transit time was observed during the morphine phase, which was significantly different from morphine with NX3G and placebo. The pain perception was not significantly influenced by NX3G. CONCLUSIONS: Orally administered NX3G is able to reverse the morphine-induced delay of CTT in humans without being detected in peripheral blood samples. Therefore, NX3G may improve symptoms of constipation in-patients using opioid medication without affecting opioid-analgesic effects.

Influence of rubber dam on objective and subjective parameters of stress during dental treatment of children and adolescents - a randomized controlled clinical pilot study

BACKGROUND Rubber dam is recommended for isolating the working field during adhesive dentistry procedures; however, dentists often omit rubber dam, particularly in paediatric dentistry, supposing that it would stress the patient. AIM The aim of this study was to evaluate stress parameters during a standardized dental treatment procedure performed with or without rubber dam. The treatment time was measured as a secondary outcome variable. DESIGN This study was designed as a randomized, controlled, clinical study with 72 patients (6-16 years; mean age, 11.1). During standardized fissure sealing procedures, objective parameters of stress (e.g., skin resistance, breath rate) were recorded. The operator's stress level was measured by pulse rate. Subjective pain (patients) and stress perception (operator) were evaluated by an interview. RESULTS The breath rate was significantly (P<0.05) lower and the skin resistance level was significantly higher during treatment with rubber dam compared to the control group. Subjective pain perception was significantly lower for the test group. The treatment time needed for the fissure sealing procedure was 12.4% less in the test group. CONCLUSION Isolation with rubber dam caused less stress in children and adolescents compared to relative isolation with cotton rolls if applied by an experienced dentist.

Treatment of lower extremity telangiectasias in women by foam sclerotherapy vs. Nd:YAG laser: a prospective, comparative, randomized, open-label trial.

BACKGROUND Telangiectasias of the lower extremities are very common. There are no blinded, randomized, controlled clinical trials comparing laser modalities with the gold standard sclerotherapy, while the few available studies encompass small patients cohorts. OBJECTIVE This prospective, randomized, open-label trial compares the efficacy of sclerotherapy with polidocanol vs. long-pulsed neodymium-doped yttrium aluminium garnet (Nd:YAG) laser in the treatment of leg telangiectasias. PATIENTS AND METHODS Fifty-six female patients with primary leg telangiectasias and reticular veins (C1A or S Ep AS 1 PN ) were included in the study. One leg was randomly assigned to get treatment with the multiple synchronized long-pulsed Nd:YAG laser, while the other received foam sclerotherapy with polidocanol 0.5%. The patients were treated in two sessions at intervals of 6 weeks. The patients were evaluated by the handling physician after 6 weeks and 6 months. Two investigators assessed blindly at the end of the study the photographs for clearing of the vessels using a six-point scale from 1 (no change) to 6 (100% cleared). Patients reported about pain sensation and outcome satisfaction. RESULTS According to the handling dermatologist, at the last follow-up, there was an improvement of 30-40% with a median of 3 (IQR 2) and a good improvement of 50-70% with a median of 4 (IQR 2) after laser treatment and sclerotherapy respectively. In contrast, according to the blinded investigators, there was a median of 5 (IQR 1) with a very good improvement of >70% after both therapies. Improvement was achieved more quickly by sclerotherapy, although at the last follow-up visit there was no difference in clearance between the two groups as assessed by the blinded experts (P-value 0.84). The degree of patient's satisfaction was very good and similar with both therapeutic approaches. There was a significant difference (P-value 0.003) regarding pain perception between the types of therapy. Laser was felt more painful than sclerotherapy. CONCLUSION Telangiectasias of the lower extremities can be successfully treated with either synchronized long-pulsed Nd:YAG laser or sclerotherapy. The 1064-nm long-pulsed Nd:YAG laser is associated with more pain and is suitable especially in case of needle phobia, allergy to sclerosants and in presence of small veins with telangiectatic matting, while sclerotherapy can also treat the feeder veins.

kappa-Opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system.

Using the mouse delta-opioid receptor cDNA as a probe, we have isolated genomic clones encoding the human mu- and kappa-opioid receptor genes. Their organization appears similar to that of the human delta receptor gene, with exon-intron boundaries located after putative transmembrane domains 1 and 4. The kappa gene was mapped at position q11-12 in human chromosome 8. A full-length cDNA encoding the human kappa-opioid receptor has been isolated. The cloned receptor expressed in COS cells presents a typical kappa 1 pharmacological profile and is negatively coupled to adenylate cyclase. The expression of kappa-opioid receptor mRNA in human brain, as estimated by reverse transcription-polymerase chain reaction, is consistent with the involvement of kappa-opioid receptors in pain perception, neuroendocrine physiology, affective behavior, and cognition. In situ hybridization studies performed on human fetal spinal cord demonstrate the presence of the transcript specifically in lamina II of the dorsal horn. Some divergences in structural, pharmacological, and anatomical properties are noted between the cloned human and rodent receptors.

Expressão dos genes codificadores de canais de sódio Nav 1.7, Nav 1.8 e Nav 1.9 em portadores da Síndrome de Ardência Bucal

A síndrome de ardência bucal (SAB) é uma condição caracterizada pelo sintoma de ardência na mucosa oral, na ausência de qualquer sinal clínico. Sua etiologia é desconhecida e, até o momento, não dispõe de tratamento efetivo. Há entretanto características de doença neuropática que justificam investigações nesse sentido. O objetivo desse estudo foi mensurar a expressão gênica dos receptores de canais de sódio, Nav 1.7, Nav 1.8 e Nav 1.9, nos pacientes portadores de SAB. A casuística foi composta por dois grupos sendo o grupo de estudo composto por 12 pacientes portadores de SAB, selecionados através do critério estabelecido pela International Headache Society, em 2013 e o grupo controle composto por 4 pacientes não portadores de SAB. As amostras analisadas foram coletadas do dorso lingual, por meio de biópsia realizada com punch de 3 mm e profundidade de 3 mm, estas foram submetidas ao método de análise RT-PCR em tempo real. A expressividade dos genes de canais de sódio foi avaliada nos indivíduos portadores de SAB em relação aos do grupo controle, sendo esta calculada a partir da normalização dos dados da quantificação destes com os da expressão do gene constitutivo (GAPDH), pelo método de Cicle Threshold comparativo e analisados estatisticamente por meio do teste estatístico Mann-Whitnney. Observou-se o aumento da expressão gênica do Nav 1.7 (fold-change = 38.70) e diminuição da expressão gênica do Nav 1.9 (fold-change = 0.89), porém sem diferenças estatisticamente significativas entre os grupos analisados. O gene Nav 1.8 não foi expresso em nenhuma das amostras analisadas. O Nav 1.7 expressa-se tanto em neurônios nociceptivos quanto no sistema nervoso autônomo e mutações no Nav 1.9 tem sido associada a perda de percepção dolorosa. Os resultados obtidos embora não estatisticamente significativos são compatíveis com as características da doença, justificando a extensão dos estudos na linha expressão de genes codificadores dos canais de sódio em pacientes com SAB.

Ensayo clínico controlado y aleatorizado para determinar los efectos del uso de pelotas de parto durante el trabajo de parto

Objetivo. Determinar los efectos del uso de la pelota de parto (PdP) durante el trabajo de parto en relación al tiempo de dilatación y expulsivo, la integridad perineal, la percepción de la intensidad del dolor y la seguridad. Método. Ensayo clínico controlado y aleatorizado. Participantes: nulíparas de 18 a 35 años, bajo riesgo, a término. Intervención: realización de movimientos sentadas sobre PdP durante el parto. Variables resultado: tiempo de dilatación y expulsivo; integridad perineal; percepción del dolor, recuerdo del dolor en el puerperio y pre-post intervención; tipo de parto; motivo de distocia; Apgar; ingreso en UCI neonatal. Análisis: comparación de grupos: t-Student para variables contínuas y Ji-cuadrado para categóricas. Significación p≤0,05. Resultados. 58 participantes (34 grupo experimental y 24 grupo control). El tiempo de dilatación y expulsivo, y la integridad perineal fue similar entre grupos. A los 4 cm el grupo experimental refirió menos dolor que el grupo control; 6,9 puntos vs 8,2 (p = 0,039). La diferencia en la percepción del dolor recordada en el puerperio inmediato fue de 1,48 puntos mayor en el grupo control (p = 0,003). La medición del dolor en el grupo experimental antes del uso de la PdP fue de 7,45 puntos y tras la intervención de 6,07 puntos (p < 0,001). En las variables relacionadas con la seguridad no hubo diferencias entre los grupos. Conclusión. El uso de pelotas de parto disminuye la percepción del dolor de parto y es segura.

Tachykinins Processing is Significantly Impaired in PC1 and PC2 Mutant Mouse Spinal Cord S9 Fractions

Substance P (SP) play a central role in nociceptive transmission and it is an agonist of the Neurokinin-1 receptor located in the lamina I of the spinal cord. SP is a major proteolytic product of the protachykinin-1 primarily synthesized in neurons. Proprotein convertases (PCs) are extensively expressed in the central nervous system (CNS) and specifically cleave at C-terminal of either a pair of basic amino acids, or a single basic residue. The proteolysis control of endogenous protachykinins has a profound impact on pain perception and the role of PCs remain unclear. The objective of this study was to decipher the role of PC1 and PC2 in the proteolysis surrogate protachykinins (i.e. Tachykinin 20-68 and Tachykinin 58-78) using cellular fractions of spinal cords from wild type (WT), PC1-/+ and PC2-/+ animals and mass spectrometry. Full-length Tachykinin 20-68 and Tachykinin 58-78 was incubated for 30 minutes in WT, PC1-/+ and PC2-/+ mouse spinal cord S9 fractions and specific C-terminal peptide fragments were identified and quantified by mass spectrometry. The results clearly demonstrate that both PC1 and PC2 mediate the formation of SP and Tachykinin 58-71, an important SP precursor, with over 50% reduction of the rate of formation in mutant PC 1 and PC2 mouse S9 spinal cord fractions. The results obtained revealed that PC1 and PC2 are involved in the C-terminal processing of protachykinin peptides and suggest a major role in the maturation of the protachykinin-1 protein.

Characterization of Endoproteolytic Processing of Dynorphins by Proprotein Convertases using Mouse Spinal Cord S9 Fractions and Mass Spectrometry

Dynorphins are important neuropeptides with a central role in nociception and pain alleviation. Many mechanisms regulate endogenous dynorphin concentrations, including proteolysis. Proprotein convertases (PCs) are widely expressed in the central nervous system and specifically cleave at C-terminal of either a pair of basic amino acids, or a single basic residue. The proteolysis control of endogenous Big Dynorphin (BDyn) and Dynorphin A (Dyn A) levels has a profound impact on pain perception and the role of PCs remain unclear. The objective of this study was to decipher the role of PC1 and PC2 in the proteolysis control of BDyn and Dyn A levels using cellular fractions of spinal cords from wild type (WT), PC1-/+ and PC2-/+ animals and mass spectrometry. Our results clearly demonstrate that both PC1 and PC2 are involved in the proteolysis regulation of BDyn and Dyn A with a more important role for PC1. C-terminal processing of BDyn generates specific peptide fragments Dynorphin 1-19, Dynorphin 1-13, Dynorphin 1-11 and Dynorphin 1-7 and C-terminal processing of Dyn A generates Dynorphin 1-13, Dynorphin 1-11 and Dynorphin 1-7, all these peptide fragments are associated with PC1 or PC2 processing. Moreover, proteolysis of BDyn leads to the formation of Dyn A and Leu-Enk, two important opioid peptides. The rate of formation of both is significantly reduced in cellular fractions of spinal cord mutant mice. As a consequence, even partial inhibition of PC1 or PC2 may impair the endogenous opioid system.

The role of protein convertases in bigdynorphin and dynorphin A metabolic pathway

Les dynorphines sont des neuropeptides importants avec un rôle central dans la nociception et l’atténuation de la douleur. De nombreux mécanismes régulent les concentrations de dynorphine endogènes, y compris la protéolyse. Les Proprotéines convertases (PC) sont largement exprimées dans le système nerveux central et clivent spécifiquement le C-terminale de couple acides aminés basiques, ou un résidu basique unique. Le contrôle protéolytique des concentrations endogènes de Big Dynorphine (BDyn) et dynorphine A (Dyn A) a un effet important sur la perception de la douleur et le rôle de PC reste à être déterminée. L'objectif de cette étude était de décrypter le rôle de PC1 et PC2 dans le contrôle protéolytique de BDyn et Dyn A avec l'aide de fractions cellulaires de la moelle épinière de type sauvage (WT), PC1 -/+ et PC2 -/+ de souris et par la spectrométrie de masse. Nos résultats démontrent clairement que PC1 et PC2 sont impliquées dans la protéolyse de BDyn et Dyn A avec un rôle plus significatif pour PC1. Le traitement en C-terminal de BDyn génère des fragments peptidiques spécifiques incluant dynorphine 1-19, dynorphine 1-13, dynorphine 1-11 et dynorphine 1-7 et Dyn A génère les fragments dynorphine 1-13, dynorphine 1-11 et dynorphine 1-7. Ils sont tous des fragments de peptides associés à PC1 ou PC2. En plus, la protéolyse de BDyn conduit à la formation de Dyn A et Leu-Enk, deux peptides opioïdes importants. La vitesse de formation des deux est réduite de manière significative dans les fractions cellulaires de la moelle épinière de souris mutantes. En conséquence, l'inhibition même partielle de PC1 ou PC2 peut altérer le système opioïde endogène.