Les mécanismes endogènes de modulation de la douleur et leur dysfonction dans le syndrome de l'intestin irritable

La douleur est une expérience subjective multidimensionnelle accompagnée de réponses physiologiques. Ces dernières sont régulées par des processus cérébraux qui jouent un rôle important dans la modulation spinale et cérébrale de la douleur. Cependant, les mécanismes de cette régulation sont encore mal définis et il est essentiel de bien les comprendre pour mieux traiter la douleur. Les quatre études de cette thèse avaient donc comme objectif de préciser les mécanismes endogènes de modulation de la douleur par la contreirritation (inhibition de la douleur par une autre douleur) et d’investiguer la dysfonction de ces mécanismes chez des femmes souffrant du syndrome de l’intestin irritable (Sii). Dans un premier temps, un modèle expérimental a été développé pour mesurer l’activité cérébrale en imagerie par résonance magnétique fonctionnelle concurremment à l’enregistrement du réflexe nociceptif de flexion (RIII : index de nociception spinale) et des réponses de conductance électrodermale (SCR : index d’activation sympathique) évoqués par des stimulations électriques douloureuses. La première étude indique que les différences individuelles d’activité cérébrale évoquée par les stimulations électriques dans les cortex orbitofrontal (OFC) et cingulaire sont associées aux différences individuelles de sensibilité à la douleur, de réactivité motrice (RIII) et de réactivité autonomique (SCR) chez des sujets sains. La deuxième étude montre que l’analgésie par contreirritation produite chez des sujets sains est accompagnée de l’inhibition de l’amygdale par OFC et d’une modulation du réflexe RIII par la substance grise périaqueducale (PAG) et le cortex somesthésique primaire (SI). Dans les troisième et quatrième études, il est montré que la contreirritation ne produit pas d’inhibition significative de la douleur et du réflexe RIII chez les patientes Sii en comparaison aux contrôles. De plus, les résultats indiquent que la sévérité des symptômes psychologiques est associée au déficit de modulation de la douleur et à une hypersensibilité diffuse chez les patientes Sii. Dans l’ensemble, cette thèse précise le rôle de certaines structures cérébrales dans les multiples composantes de la douleur et dans l’analgésie par contreirritation et montre que les patientes Sii présentent une dysfonction des mécanismes spinaux et cérébraux impliqués dans la perception et la modulation de la douleur.

Corticomuscular coherence modulation with the pattern of finger force coordination

We assess the corticomuscular coherence (CMC) of the contralateral primary motor cortex and the hand muscles during a finger force-tracking task and explore whether the pattern of finger coordination has an impact on the CMC level. Six healthy subjects (three men and three women) were recruited to conduct the force-tracking tasks comprising two finger patterns, i.e., natural combination of index and middle fingers and unnatural combination of index and middle fingers (i.e., simultaneously producing equal force strength in index and middle finger). During the conducting of the tasks with right index and middle finger, MEG and sEMG signals were recorded from left primary motor cortex (M1) and right flexor digitorum superficialis (FDS), respectively; the contralateral CMC was calculated to assess the neuromuscular interaction. Finger force-tracking tasks of Common-IM only induce beta-band CMC, whereas Uncommon-IM tasks produce CMC in both beta and low-gamma band. Compared to the force-tracking tasks of Common-IM, the Uncommon-IM task is associated with the most intensive contralateral CMC. Our study demonstrated that the pattern of finger coordination had significant impact on the CMC between the contralateral M1 and hand muscles, and more corticomuscular interaction was necessary for unnaturally coordinated finger activities to regulate the fixed neural drive of hand muscles.

Involvement of proteinase-activated receptors 1 and 2 in spreading and phagocytosis by murine adherent peritoneal cells: Modulation by the C-terminal of S100A9 protein

Proteinase-activated receptors (PAR) are widely recognized for their modulatory properties in inflammatory and immune responses; however, their direct role on phagocyte effector functions remains unknown. S100A9, a protein secreted during inflammatory responses, deactivates activated peritoneal macrophages, and its C-terminal portion inhibits spreading and phagocytosis of adherent peritoneal cells. Herein, the effect of PAR1 and PAR2 agonists was investigated on spreading and phagocytosis by adherent peritoneal cells, as well as the ability of murine C-terminal of S100A9 peptide (mS100A9p) to modulate this effect. Adherent peritoneal cells obtained from mouse abdominal cavity were incubated with PAR1 and PAR2 agonists and spreading and phagocytosis of Candida albicans particles were evaluated. PAR1 agonists increased both the spreading and the phagocytic activity, but PAR2 agonists only increased the spreading index. mS100A9p reverted both the increased spreading and phagocytosis induced by PAR1 agonists, but no interference in the increased spreading induced by PAR2 agonists was noticed. The shorter homologue peptide to the C-terminal of mS100A9p, corresponding to the H(92)-E(97) region, also reverted the increased spreading and phagocytosis induced by PAR1 agonists. These findings show that proteinase-activated receptors have an important role for spreading and phagocytosis of adherent peritoneal cells, and that the pepticle corresponding to the C-terminal of S100A9 protein is a remarkable candidate for use as a novel compound to modulate PAR1 function. (C) 2009 Elsevier B.V. All rights reserved.

Modulation of tumor necrosis factor receptors 1 and 2 in chronic hepatitis B and C: The differences and implications in pathogenesis

Tumor necrosis factor (TNF) plays a role in the pathogenesis of chronic hepatitis B (CHB) and chronic hepatitis C (CHC). The difference in the cytokine responses between hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may have implications in the pathogenesis of these diseases. We performed a comparative study to examine the possible differences in the TNF-TNF receptor (TNFR) response between CHB and CHC. We studied the cytokine levels of 38 patients with CHB, 40 patients with CHC and 9 patients with dual hepatitis B and C, and compared them with the baseline levels of 12 healthy controls. The plasma levels of TNF-, interferon-, interleukin (IL)-2, IL-4, IL-10 and soluble TNFR-1 and 2 (sTNFR-1 and 2) were quantified by enzyme-linked immunosorbent assays. The expression of TNFR-1 and 2 in liver tissues was examined in 30 cases of CHB and 15 cases of CHC by semiquantitative reverse transcription polymerase chain reaction. The results showed that sTNFR-1 levels correlated with liver inflammation in all patients, whereas this correlation was not found with sTNFR-2 or other cytokines. Liver inflammation indicators were higher in HCV RNA+ than in HCV RNA– CHC. Most significantly, sTNFR-1 levels correlated with liver inflammation in CHB, but not in CHC. However, the expression of TNFR-1 and 2 in liver was similar between CHB and CHC. These findings suggest that the TNFR signal transduction pathway is modulated differently in HBV and HCV infection.

Breakdown in central motor control can be attenuated by motor practice and neuro-modulation of the primary motor cortex

The performance of a repetitive index finger flexion–extension task at maximal voluntary rate (MVR) begins to decline just a few seconds into the task and we have previously postulated that this breakdown has a central origin. To test this hypothesis, we have combined two objectives; to determine whether motor practice can lessen the performance deterioration in an MVR task, and whether further gains can be achieved with a transcranial magnetic stimulation (TMS) protocol that increases corticomotor excitability (CME). Eleven right-handed subjects participated in a randomized crossover study design that consisted of a 15-min interventional TMS at I-wave periodicity (ITMS) and single-pulsed Sham intervention prior to six 10-s practice sets of a repetitive finger flexion–extension task at MVR. Motor-evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle. The starting movement rate, and the percentage decline in rate by the end of the MVR were quantitated. Training of the MVR task improved the sustainability of the task by reducing the decline in movement rate. CME increased steadily after each training bout, and this increase was maintained up to 20 min after the last bout. ITMS further increased CME, and was associated with an increase in both the starting rate of the MVR task and its sustainability, when compared to Sham. The results implicate central motor processes in the performance and sustainability of the MVR task, and indicate that MVR kinematics can improve with short-term training and with non-invasive neuro-modulation.

Modulation of corticomotor excitability after maximal or sustainable-rate repetitive finger movement is impaired in Parkinson’s disease and is reversed by levodopa

Objectives: In healthy subjects, fatiguing exercises induce a period of post-exercise corticomotor depression (PECD) that is absent in Parkinson’s disease (PD). Our objective is to determine the time-course of corticomotor excitability changes following a 10-s repetitive index finger flexion–extension task performed at maximal voluntary rate (MVR) and a slower sustainable rate (MSR) in PD patients OFF and ON levodopa.
Methods: In 11 PD patients and 10 healthy age-matched controls, motor evoked potentials (MEPs) were recorded from the extensor indicis proprius (EIP) and first dorsal interosseous (FDI) muscles of the dominant arm immediately after the two tasks and at 2-min intervals for 10 min.
Results: In the OFF condition the PECD was absent in the two test muscles after both the MVR and MSR tasks. In the ON condition finger movement kinematics improved and a period of PECD comparable to that in controls was present after both tasks.
Conclusion: The absence of PECD in PD subjects off medication indicates a persisting increase in corticomotor excitability after non-fatiguing repetitive finger movement that is reversed by levodopa.

Analysis of cardiac autonomic modulation in obese and eutrophic children

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Strong and fast phase modulation for quantitative analysis of photorefractive gratings

A new approach for studying photorefractive gratings in two-wave mixing experiments by a phase modulation technique is presented. The introduction of a large-amplitude, high-frequency sinusoidal phase modulation in one of the input beams blurs the interference pattern and provides powerful harmonic signals for accurate measurements of the grating diffraction efficiency eta and the output phase shift rho between the transmitted and diffracted waves. The blurring of the light fringes can be used to suppress the higher spatial harmonics of the grating, allowing a space-charge field with sinusoidal profile to be recorded. Although the presence of such a strong phase modulation affects the beam coupling in a rather complicated way, it is shown that for the special case of equal intensity input beams, the effect of the phase modulation on eta and rho is reduced to a weakening of the coupling strength. The potentialities of the technique are illustrated in a study of refractive-index waves excited by running interference patterns in a Bi12TiO20 crystal. Expressions for the diffraction efficiency and the output phase shift are derived and used to match numerically calculated curves to the experimental data. The theoretical model is supported by the very good data fitting and allows the computation of important material parameters.

Photoperiod modulation of aggressive behavior is independent of androgens in a tropical cichlid fish

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Response of cardiac autonomic modulation after a single exposure to musical auditory stimulation

The acute effects after exposure to different styles of music on cardiac autonomic modulation assessed through heart rate variability (HRV) analysis have not yet been well elucidated. We aimed to investigate the recovery response of cardiac autonomic modulation in women after exposure to musical auditory stimulation of different styles. The study was conducted on 30 healthy women aged between 18 years and 30 years. We did not include subjects having previous experience with musical instruments and those who had an affinity for music styles. The volunteers remained at rest for 10 min and were exposed to classical baroque (64-84 dB) and heavy metal (75-84 dB) music for 10 min, and their HRV was evaluated for 30 min after music cessation. We analyzed the following HRV indices: Standard deviation of normal-to-normal (SDNN) intervals, root mean square of successive differences (RMSSD), percentage of normal-to-normal 50 (pNN50), low frequency (LF), high frequency (HF), and LF/HF ratio. SDNN, LF in absolute units (ms (2) ) and normalized (nu), and LF/HF ratio increased while HF index (nu) decreased after exposure to classical baroque music. Regarding the heavy metal music style, it was observed that there were increases in SDNN, RMSSD, pNN50, and LF (ms (2) ) after the musical stimulation. In conclusion, the recovery response of cardiac autonomic modulation after exposure to auditory stimulation with music featured an increased global activity of both systems for the two musical styles, with a cardiac sympathetic modulation for classical baroque music and a cardiac vagal tone for the heavy metal style.

Analysis of autonomic modulation after an acute session of resistance exercise at different intensities in chronic obstructive pulmonary disease patients

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Impact of obesity on autonomic modulation, heart rate and blood pressure in obese young people

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Nitric oxide is responsible for oxidative skin injury and modulation of cell proliferation after 24 hours of UVB exposures

Nitric oxide (NO) is produced by various mammalian cells and plays a variety of regulatory roles in normal physiology and in pathological processes. This article provides evidence regarding the participation of NO in UVB-induced skin lesions and in the modulation of skin cell proliferation following UVB skin irradiation. Hairless mice were subjected to UVB irradiation for 3 hours and the skin evaluated immediately, 6 and 24 hours postirradiation. The skin lipid peroxidation, and NO levels evaluated by chemiluminescence and inducible nitric oxide synthase (iNOS) and nitrotyrosine immunolabelling increased significantly 24 hours after irradiation and decreased under the treatment with aminoguanidine (AG). On the other hand, cell proliferation markers, PCNA and VEGF showed a strong labelling index when AG was used. The data indicate that NO mediates, at least in part, the lipid peroxidation and protein nitration and also promotes the down regulation of factors involved in cell proliferation. This work shows that the NO plays an important role in the oxidative stress damage and on modulation of cell proliferation pathways in UVB irradiated skin.

Effect of patient size on radiation dose for abdominal MDCT with automatic tube current modulation: phantom study

OBJECTIVE: The purpose of this study was to evaluate in a phantom study the effect of patient size on radiation dose for abdominal MDCT with automatic tube current modulation. MATERIALS AND METHODS: One or two 4-cm-thick circumferential layers of fat-equivalent material were added to the abdomen of an anthropomorphic phantom to simulate patients of three sizes: small (cross-sectional dimensions, 18 x 22 cm), average size (26 x 30 cm), and oversize (34 x 38 cm). Imaging was performed with a 64-MDCT scanner with combined z-axis and xy-axis tube current modulation according to two protocols: protocol A had a noise index of 12.5 H, and protocol B, 15.0 H. Radiation doses to three abdominal organs and the skin were assessed. Image noise also was measured. RESULTS: Despite increasing patient size, the image noise measured was similar for protocol A (range, 11.7-12.2 H) and protocol B (range, 13.9-14.8 H) (p > 0.05). With the two protocols, in comparison with the dose of the small patient, the abdominal organ doses of the average-sized patient and the oversized patient increased 161.5-190.6%and 426.9-528.1%, respectively (p < 0.001). The skin dose increased as much as 268.6% for the average-sized patient and 816.3% for the oversized patient compared with the small patient (p < 0.001). CONCLUSION: Oversized patients undergoing abdominal MDCT with tube current modulation receive significantly higher doses than do small patients. The noise index needs to be adjusted to the body habitus to ensure dose efficiency.