Effect of Deep Intramuscular Stimulation and Transcranial Magnetic Stimulation on Neurophysiological Biomarkers in Chronic Myofascial Pain Syndrome.

OBJECTIVE: The aim was to assess the neuromodulation techniques effects (repetitive transcranial magnetic stimulation [rTMS] and deep intramuscular stimulation therapy [DIMST]) on pain intensity, peripheral, and neurophysiological biomarkers chronic myofascial pain syndrome (MPS) patients. DESIGN: Randomized, double blind, factorial design, and controlled placebo-sham clinical trial. SETTING: Clinical trial in the Laboratory of Pain and Neuromodulation at Hospital de Clínicas de Porto Alegre (NCT02381171). SUBJECTS: We recruited women aged between 19- and 75-year old, with MPS diagnosis. METHODS: Patients were randomized into four groups: rTMS + DIMST, rTMS + sham-DIMST, sham-rTMS + DIMST, sham-rTMS + sham-DIMST; and received 10 sessions for 20 minutes each one (rTMS and DIMST). Pain was assessed by visual analogue scale (VAS); neurophysiological parameters were assessed by transcranial magnetic stimulation; biochemical parameters were: BDNF, S100ß, lactate dehydrogenase, inflammatory (TNF-α, IL6, and IL10), and oxidative stress parameters. RESULTS: We observed the pain relief assessed by VAS immediately assessed before and after the intervention (P < 0.05, F(1,3)= 3.494 and F(1,3)= 4.656, respectively); in the sham-rTMS + DIMST group and both three active groups in relation to sham-rTMS + sham-DIMST group, respectively. There was an increase in the MEP after rTMS + sham-DIMST (P < 0.05). However, there was no change in all-peripheral parameters analyzed across the treatment (P > 0.05). CONCLUSION: Our findings add additional evidence about rTMS and DIMST in relieving pain in MPS patients without synergistic effect. No peripheral biomarkers reflected the analgesic effect of both techniques; including those related to cellular damage. Additionally, one neurophysiological parameter (increased MEP amplitude) needs to be investigated.

Modulation of apoptosis by sulforaphane is associated with PGC-1α stimulation and decreased oxidative stress in cardiac myoblasts.

Sulforaphane is a naturally occurring isothiocyanate capable of stimulating cellular antioxidant defenses and inducing phase 2 detoxifying enzymes, which can protect cells against oxidative damage. Oxidative stress and apoptosis are intimately involved in the pathophysiology of cardiac diseases. Although sulforaphane is known for its anticancer benefits, its role in cardiac cells is just emerging. The aim of the present study was to investigate whether sulforaphane can modulate oxidative stress, apoptosis, and correlate with PGC-1α, a transcriptional cofactor involved in energy metabolism. H9c2 cardiac myoblasts were incubated with R-sulforaphane 5 µmol/L for 24 h. Cell viability, ANP gene expression, oxidative stress and apoptosis markers, and protein expression of PGC-1α were studied. In cells treated with sulforaphane, cellular viability increased (12 %) and ANP gene expression decreased (46 %) compared to control cells. Moreover, sulforaphane induced a significant increase in superoxide dismutase (103 %), catalase (101 %), and glutathione S-transferase (72 %) activity, reduced reactive oxygen species levels (15 %) and lipid peroxidation (65 %), as well as stimulated the expression of the cytoprotective enzyme heme oxygenase-1 (4-fold). Sulforaphane also promoted an increase in the expression of the anti-apoptotic protein Bcl-2 (60 %), decreasing the Bax/Bcl-2 ratio. Active Caspase 3\7 and p-JNK/JNK were also reduced by sulforaphane, suggesting a reduction in apoptotic signaling. This was associated with an increased protein expression of PGC-1α (42 %). These results suggest that sulforaphane offers cytoprotection to cardiac cells by activating PGC1-α, reducing oxidative stress, and decreasing apoptosis signaling.

Effects of thyroid hormones on aortic tissue after myocardial infarction in rats.

Studies have shown a cardioprotective role of thyroid hormones (THs) in cardiac remodeling after acute myocardial infarction (MI). However, there is no data in the literature examining the influence of TH administration on the aortic tissue in an animal model of MI. This study aimed to evaluate the effects of thyroid hormones on the aorta after MI. Male Wistar rats were divided into a sham group (SHAM), infarcted group (AMI), sham+TH (SHAMT) and AMI+TH (AMIT). After MI, the animals received T3 and T4 (2 and 8µg/100g/day, respectively) by oral gavage for 12 days. Later, the animals underwent echocardiography and euthanasia and the aorta was collected for molecular and biochemical analysis. T3 and T4 administration increased the expression of the pro-angiogenic proteins vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1α (HIF-1α) in the aorta of AMIT rats when compared with AMI. With respect to TH receptors, AMI rats presented a decrease in TRß levels, which was prevented by the hormonal administration. In AMIT rats, both TRα and TRß levels were increased when compared with the AMI group. Reactive oxygen species levels and NADPH oxidase activity were decreased in both treated groups when compared with the non-treated animals. TH administration after MI may improve angiogenic signaling in the aorta as well as the responsiveness of this vessel to T3 and T4. These positive effects in the aorta may result in additional protection for the cardiovascular system in the context of cardiac ischaemic injury.

Thyroid hormones effects on oxidative stress and cardiac remodeling in the right ventricle of infarcted rats.

UNLABELLED: Right ventricle (RV) dysfunction post-myocardial infarction (MI) was associated with a worsened prognosis. In this scenario, reactive oxygen species (ROS) are related with the progression from MI to heart failure. Previous work showed that thyroid hormones (TH) are cardioprotective after MI. AIMS: This study aims to investigate the effect of T3 and T4 administration on oxidative stress and angiogenesis parameters in the RV after MI. MAIN METHODS: Wistar rats were allocated into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT), and infarcted+TH (AMIT). The treated groups received T3 (2 µg/100g/day) and T4 (8 µg/100g/day) by gavage for 26 days. After this, echocardiographic analysis was performed and the RV was collected to western blot and biochemical analysis. KEY FINDINGS: Infarcted treated rats showed RV hypertrophy compared with AMI and SHAMT. Hydrogen peroxide levels were decrease and SOD activity and expression were increased in the infarcted treated rats. Besides that, the hormonal administration increased eNOS expression and prevented the reduction of VEGF levels in AMIT rats. SIGNIFICANCE: In conclusion, TH seems to improve oxidative stress parameters, to promote physiological hypertrophy and to increase the expression of proteins involved with angiogenesis in the right heart.