RESUMEN
Previous studies have found that obesity could influence academic performance. The aim of this study was to systematically review the scientific evidence on the association between obesity and academic performance in school children. A systematic review of English articles was undertaken by using databases PubMed/Medline, ERIC, LILACS, SciELO and Web of Science. Cross-sectional and longitudinal studies examining the association between obesity and academic performance in children and adolescents, published between January 1990 and December 2016, were included. Risk of bias was assessed by using Strengthening the Reporting of Observational Studies in Epidemiology. Thirty-four studies (23 cross-sectional and 11 longitudinal) matched all inclusion criteria and were included. Seven studies were classified as low risk of bias, 23 as medium risk and four as high risk. After controlling for covariates such as socio-economic status, parental education and physical activity, the association between obesity and academic performance becomes uncertain for most of the studies (55.9%). Therefore, at present, there is insufficient evidence to support a direct link between obesity and poor academic performance in school age children. In order to clarify this issue, we need more longitudinal studies with adequate sample sizes and that control for potential confounders.
Asunto(s)
Rendimiento Académico , Obesidad/psicología , Niño , HumanosRESUMEN
BACKGROUND: The association between obesity during adolescence and the increased risk of cardiometabolic diseases indicates the need to identify reproducible and cost effective methods for identifying individuals who are at increased risk of developing diseases. The present cross-sectional study investigated the occurrence of metabolic consequences of obesity in adolescents and the use of adiposity indicators as predictors of cardiometabolic risk. METHODS: A fasting blood sample was taken in 93 pubertal obese adolescents aged 13-18 years old (39 males, 54 females) for the assessment of cardiometabolic risk markers (glucose, lipid profiles, insulin resistence, and inflammatory and endothelial dysfunction markers). Together with anthropometry, total fat mass and lean mass were determined by dual-energy X-ray absorptiometry (DXA). RESULTS: The prevalence of dyslipidaemia and disorders in glucose metabolism are noticeably higher in the present study. There was no correlation between the percentage of body fat according to DXA and most indicators of adiposity. For boys, the arm circumference values predicted the increase in fasting insulin (r² = 0.200), homeostasis model assessment of insulin resistance (r² = 0.267) and cardiometabolic risk score (r² = 0.338). The percentage of body fat according to DXA predicted the inflammation score (r² = 0.172). For girls, body mass index was the parameter that best described the variability of fasting insulin (r² = 0.079) and inflammation score (r² = 0.263). The waist-to-stature ratio was able to predict the triglyceride values (r² = 0.090). CONCLUSIONS: Anthropometric measures of adiposity, such a body mass index, waist-to-stature ratio, arm circumference and waist circumference,should be considered in the clinical evaluation of obese adolescents.
Asunto(s)
Adiposidad , Composición Corporal , Enfermedades Cardiovasculares/sangre , Síndrome Metabólico/sangre , Obesidad Infantil/sangre , Absorciometría de Fotón , Adolescente , Biomarcadores/sangre , Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , Colesterol/sangre , Estudios Transversales , Femenino , Humanos , Insulina/sangre , Resistencia a la Insulina , Masculino , Síndrome Metabólico/epidemiología , Obesidad Infantil/complicaciones , Factores de Riesgo , Triglicéridos/sangre , Circunferencia de la CinturaRESUMEN
Physical fitness (PF) is a construct of health- and skill-related attributes which have been associated with academic performance (AP) in youth. This study aimed to review the scientific evidence on the association among components of PF and AP in children and adolescents. A systematic review of articles using databases PubMed/Medline, ERIC, LILACS, SciELO, and Web of Science was undertaken. Cross-sectional and longitudinal studies examining the association between at least one component of PF and AP in children and adolescents, published between 1990 and June 2016, were included. Independent extraction of articles was carried out by the two authors using predefined data fields. From a total of 45 studies included, 25 report a positive association between components of PF with AP and 20 describe a single association between cardiorespiratory fitness (CRF) and AP. According to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines: 12 were classified as low, 32 as medium risk, and 1 as high risk of bias. Thirty-one studies reported a positive association between AP and CRF, six studies with muscular strength, three studies with flexibility, and seven studies reported a positive association between clustered of PF components and AP. The magnitude of the associations is weak to moderate (ß = 0.10-0.42 and odds = 1.01-4.14). There is strong evidence for a positive association between CRF and cluster of PF with AP in cross-sectional studies; and evidence from longitudinal studies for a positive association between cluster of PF and AP; the relationship between muscular strength and flexibility with AP remains uncertain.
Asunto(s)
Logro , Escolaridad , Aptitud Física , Adolescente , Capacidad Cardiovascular , Niño , Humanos , Fuerza Muscular , Rango del Movimiento ArticularRESUMEN
BACKGROUND AND AIMS: While studies have described the importance of higher physical activity levels (PAL) in weight loss, the impact of self-initiated PAL on health status warrants further study. We aimed to prospectively examine the effects of self-initiated longitudinal PAL changes on body mass index (BMI) and cardiometabolic parameters in normal weight, overweight and obese adults. METHODS AND RESULTS: We included 4840 adults (mean age 41.6 ± 7.9 years, 79% male) undergoing routine health screening examinations. Self-reported PAL, height, weight, blood pressure and blood samples were collected at baseline and after a mean (95% confidence interval) follow up of 536 (531-541) days. Subjects were stratified according to BMI [39.8% normal weight (<25 kg/m2), 45.1% overweight (25.0-29.9 kg/m2), and 19.1% obese (≥30 kg/m2)]. In normal weight individuals, BMI increased from baseline to follow-up, irrespective of PAL changes. On the other hand, overweight and obese individuals that increased PAL experienced a decrease in BMI by -0.9% and -3.1%, respectively (p < 0.05). Overweight and obese individuals that increased PAL also experienced a decrease in -5.8% -4.6% in non-HDL concentrations from baseline to follow-up (p < 0.05). Finally, in overweight individuals, LDL cholesterol concentrations decreased from baseline to follow-up, irrespective of PAL changes whereas in obese individuals, a maintenance or increased PAL were associated with a decrease in -4.7% and -6.1% (p < 0.05), respectively. CONCLUSIONS: In a large cohort of screening patients, longitudinal self-initiated PAL is associated with improved BMI and cardiometabolic profile in overweight and obese individuals.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Ejercicio Físico , Hábitos , Síndrome Metabólico/prevención & control , Obesidad/prevención & control , Conducta de Reducción del Riesgo , Autocuidado , Adulto , Índice de Masa Corporal , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Lípidos/sangre , Estudios Longitudinales , Masculino , Síndrome Metabólico/etiología , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Estado Nutricional , Obesidad/complicaciones , Obesidad/diagnóstico , Obesidad/fisiopatología , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Pérdida de PesoRESUMEN
The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeare to be a good candidate to maximize follicular targeting and minimize drug penetration into the interfollicular epidermis. We conclude that such nanotechnology-based formulations provide a viable strategy for more efficient drug delivery to the hair follicle. Moreover, they present a way to minimize adverse effects of potent glucocorticoids by releasing the drug in a controlled manner and simultaneously decreasing interfollicular permeation, offering an advantage over conventional formulations for inflammatory-based skin/scalp diseases.
Asunto(s)
Antiinflamatorios/administración & dosificación , Clobetasol/administración & dosificación , Folículo Piloso/metabolismo , Nanocápsulas/administración & dosificación , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacocinética , Clobetasol/química , Clobetasol/farmacocinética , Liberación de Fármacos , Humanos , Hidrogeles , Estimulación Física , Poliésteres/química , PorcinosRESUMEN
The mechanisms underlying improvement of neuromuscular transmission deficits by glucocorticoids are still a matter of debate despite these compounds have been used for decades in the treatment of autoimmune myasthenic syndromes. Besides their immunosuppressive action, corticosteroids may directly facilitate transmitter release during high-frequency motor nerve activity. This effect coincides with the predominant adenosine A2A receptor tonus, which coordinates the interplay with other receptors (e.g. muscarinic) on motor nerve endings to sustain acetylcholine (ACh) release that is required to overcome tetanic neuromuscular depression in myasthenics. Using myographic recordings, measurements of evoked [(3)H]ACh release and real-time video microscopy with the FM4-64 fluorescent dye, results show that tonic activation of facilitatory A2A receptors by endogenous adenosine accumulated during 50 Hz bursts delivered to the rat phrenic nerve is essential for methylprednisolone (0.3 mM)-induced transmitter release facilitation, because its effect was prevented by the A2A receptor antagonist, ZM 241385 (10 nM). Concurrent activation of the positive feedback loop operated by pirenzepine-sensitive muscarinic M1 autoreceptors may also play a role, whereas the corticosteroid action is restrained by the activation of co-expressed inhibitory M2 and A1 receptors blocked by methoctramine (0.1 µM) and DPCPX (2.5 nM), respectively. Inhibition of FM4-64 loading (endocytosis) by methylprednisolone following a brief tetanic stimulus (50 Hz for 5 s) suggests that it may negatively modulate synaptic vesicle turnover, thus increasing the release probability of newly recycled vesicles. Interestingly, bulk endocytosis was rehabilitated when methylprednisolone was co-applied with ZM241385. Data suggest that amplification of neuromuscular transmission by methylprednisolone may involve activation of presynaptic facilitatory adenosine A2A receptors by endogenous adenosine leading to synaptic vesicle redistribution.
Asunto(s)
Metilprednisolona/farmacología , Unión Neuromuscular/metabolismo , Terminales Presinápticos/metabolismo , Receptor de Adenosina A2A/metabolismo , Vesículas Sinápticas/metabolismo , Animales , Células CACO-2 , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Unión Neuromuscular/efectos de los fármacos , Terminales Presinápticos/efectos de los fármacos , Ratas , Ratas Wistar , Vesículas Sinápticas/químicaRESUMEN
BACKGROUND: The anterior pretectal nucleus (APtN) activates descending mechanisms of pain control. This study evaluated whether the APtN also controls neuropathic pain in rats. METHODS: The hypersensitivity to mechanical stimulation with an electronic von Frey apparatus and the number of Fos-immunoreactive (Fos-ir) neurons in the APtN were evaluated in rats before and after chronic constriction injury of the sciatic nerve. RESULTS: The tactile hypersensitivity was characterized by an initial phase (the 2 days following the injury) and a maintenance phase (the subsequent 7 days). The injection of 2% lidocaine (0.25 µL) or N-methyl-D-aspartate (2.5 µg/0.25 µL) into the APtN intensified the tactile hypersensitivity observed 2 days after injury but did not alter the tactile hypersensitivity observed 7 and 14 days after injury. The injection of naloxone (10 ng/0.25 µL) or methysergide (40 pg/0.25 µL) but not atropine (100 ng/0.25 µL) into the APtN also intensified the tactile hypersensitivity observed 2 days after the injury. A significant increase in the number of Fos-ir cells was found in the contralateral APtN 2 days but not 7 or 14 days after the injury. Electrical stimulation of the APtN reduced the tactile hypersensitivity at 2, 7 and 14 days after the nerve ligation. CONCLUSION: APtN exerts a tonic inhibitory influence on persistent pain. The results point out to an important role of opioid and serotonergic mediation into the APtN to inhibit hyperalgesia during the initial phase of neuropathic pain.
Asunto(s)
Vías Nerviosas/patología , Neuralgia/patología , Área Pretectal/patología , Anestésicos Locales/administración & dosificación , Anestésicos Locales/farmacología , Animales , Constricción Patológica/complicaciones , Constricción Patológica/patología , Hiperalgesia/fisiopatología , Lidocaína/administración & dosificación , Lidocaína/farmacología , Masculino , Metisergida/farmacología , N-Metilaspartato/administración & dosificación , N-Metilaspartato/farmacología , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Neuronas/patología , Dimensión del Dolor/efectos de los fármacos , Estimulación Física , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Wistar , Neuropatía Ciática/patologíaRESUMEN
BACKGROUND: Aerobic exercise improves cardiovascular health in general, but whether the impact varies with exercise intensity is not clear. OBJECTIVE: The aim of the current study was to compare the effects of a high-intensity aerobic exercise training (HIT) vs. a low-intensity aerobic exercise training (LIT) on blood pressure (BP), heart rate (HR) and heart rate variability (HRV) in obese adolescents. METHODS: Forty-three (13-18 years) Tanner stage (III-IV) matched obese adolescents were studied in a randomized trial of either HIT (corresponding to the ventilatory threshold I; n = 20) or LIT (corresponding to 20% below the ventilatory threshold I; n = 23) programme for a period of 6 months. All participants also received a multidisciplinary therapy that included nutritional, psychological and clinical counselling. Both HIT and LIT sessions were isocaloric, with energy expenditure set at 350 kcal. BP, HR and HRV were measured along with markers of body adiposity and insulin resistance before and after the respective interventions. RESULTS: The participants in both groups had similar physical and clinical characteristics. After the 6-month intervention, systolic, diastolic and mean BP decreased (P < 0.05, for all) similarly in both groups, whereas waist circumference, HR and HRV showed beneficial changes only in the HIT group (P < 0.05). CONCLUSION: Aerobic exercise training set at a high intensity compared with the low intensity appears to have additional benefits on abdominal obesity and cardiovascular health in that it enhances the parasympathetic and autonomic modulation of the heart in obese adolescents.
Asunto(s)
Presión Sanguínea , Enfermedades Cardiovasculares/prevención & control , Ejercicio Físico , Frecuencia Cardíaca , Obesidad/complicaciones , Esfuerzo Físico , Aptitud Física , Adolescente , Brasil/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Metabolismo Energético , Femenino , Humanos , Masculino , Obesidad/epidemiología , Obesidad/fisiopatología , Pubertad , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIM: Objective of the study was to determine the effects of a periodized resistance training program on body composition, plasmatic levels of leptin and resistin, and muscle strength in elderly post-menopausal women. METHODS: Twenty-three post-menopausal women (age= 63.02±4.42 years; height 1.55±0.06 m; body mass 67.56±2.26 kg) were submitted to 12 months of periodized resistance training twice a week. The training program consisted of 3 sets of 6-14 repetitions maximal (RM). Body composition (DXA), muscle strength (bench press, leg press 45º and arm curl), plasmatic levels of resistin and leptin (ELISA method) were assessed before and after the training program. Paired Student's t test was used for comparison between pre- and post-training values. RESULTS: There was a significant increase in muscle strength and lean body mass; decrease in body mass, body fat percentage and fat mass after 12 months of resistance training, a part from the decrease in leptin and resistin levels. CONCLUSION: Long-term periodized resistance training prevents aging sarcopenia, decreases body fat and systemic markers of inflammation in postmenopausal elderly women.
Asunto(s)
Distribución de la Grasa Corporal , Leptina/sangre , Fuerza Muscular/fisiología , Entrenamiento de Fuerza/métodos , Resistina/sangre , Anciano , Femenino , Humanos , Persona de Mediana Edad , Posmenopausia/fisiologíaRESUMEN
A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively) similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively), but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively). The modified method required less surgical skill than the spinal nerve ligation model.
Asunto(s)
Umbral del Dolor/fisiología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Nervio Ciático/lesiones , Animales , Modelos Animales de Enfermedad , Hiperalgesia/fisiopatología , Masculino , Dimensión del Dolor , Enfermedades del Sistema Nervioso Periférico/etiología , Ratas Wistar , Factores de TiempoRESUMEN
A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively) similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively), but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively). The modified method required less surgical skill than the spinal nerve ligation model.
Asunto(s)
Animales , Masculino , Umbral del Dolor/fisiología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Nervio Ciático/lesiones , Modelos Animales de Enfermedad , Hiperalgesia/fisiopatología , Dimensión del Dolor , Enfermedades del Sistema Nervioso Periférico/etiología , Ratas Wistar , Factores de TiempoRESUMEN
Angiotensins (Angs) modulate blood pressure, hydro-electrolyte composition, and antinociception. Although Ang (5-8) has generally been considered to be inactive, we show here that Ang (5-8) was the smallest Ang to elicit dose-dependent responses and receptor-mediated antinociception in the rat ventrolateral periaqueductal gray matter (vlPAG). Ang (5-8) antinociception seems to be selective, because it did not alter blood pressure or act on vascular or intestinal smooth muscle cells. The non-selective Ang-receptor (Ang-R) antagonist saralasin blocked Ang (5-8) antinociception, but selective antagonists of Ang-R types I, II, IV, and Mas did not, suggesting that Ang (5-8) may act via an unknown receptor. Endopeptidase EP 24.11 and amastatin-sensitive aminopeptidase from the vlPAG catalyzed the synthesis (from Ang II or Ang III) and inactivation of Ang (5-8), respectively. Selective inhibitors of neuronal-nitric oxide (NO) synthase, soluble guanylyl cyclase (sGC) and a non-selective opioid receptor (opioid-R) inhibitor blocked Ang (5-8)-induced antinociception. In conclusion, Ang (5-8) is a new member of the Ang family that selectively and strongly modulates antinociception via NO-sGC and endogenous opioid in the vlPAG.
Asunto(s)
Angiotensina I/farmacología , Guanilato Ciclasa/metabolismo , Óxido Nítrico/metabolismo , Nocicepción/efectos de los fármacos , Péptidos Opioides/metabolismo , Fragmentos de Péptidos/farmacología , Sustancia Gris Periacueductal/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/metabolismo , Transducción de Señal/efectos de los fármacos , Antagonistas de Receptores de Angiotensina/farmacología , Animales , Aorta/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Frecuencia Cardíaca/fisiología , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Péptidos Opioides/antagonistas & inhibidores , Ratas , Ratas Wistar , Saralasina/farmacología , Guanilil Ciclasa Soluble , Teprotido/farmacologíaRESUMEN
AIMS: The purpose of this study was to examine whether the use of intraperitoneal or intrathecal amitriptyline combined with electroacupuncture modifies the tail-flick reflex and incision pain in rats that normally do not have analgesia to electroacupuncture in the tail-flick test (non-responder rats). MAIN METHODS: Changes in the nociceptive threshold of intraperitoneal or intrathecal saline- or amitriptyline-treated non-responder rats were evaluated using the tail-flick or incision pain tests before, during and after a 20-min period of electroacupuncture, applied at 2 Hz to the Zusanli and Sanynjiao acupoints. Amitriptyline was used at doses of 0.8 mg/kg or 30 µg/kg by intraperitoneal or intrathecal route, respectively. At these doses, amitriptyline has no effect against thermal or incision pain in rats. KEY FINDINGS: Rats selected as non-responders to the analgesic effect of electroacupuncture 2 Hz in tail-flick and incision pain tests become responders after an intraperitoneal or intrathecal injection of amitriptyline. SIGNIFICANCE: Amitriptyline converts non-responder rats to rats that respond to electroacupuncture with analgesia in a model of thermal phasic pain and anti-hyperalgesia in a model of incision pain.
Asunto(s)
Amitriptilina/uso terapéutico , Electroacupuntura , Dolor Nociceptivo/terapia , Umbral del Dolor/efectos de los fármacos , Analgésicos no Narcóticos/uso terapéutico , Animales , Terapia Combinada , Infusiones Parenterales , Inyecciones Espinales , Masculino , Ratas , Ratas WistarRESUMEN
AIM: This study examines if injection of cobalt chloride (CoCl(2)) or antagonists of muscarinic cholinergic (atropine), µ(1)-opioid (naloxonazine) or 5-HT(1) serotonergic (methiothepin) receptors into the dorsal or ventral portions of the anterior pretectal nucleus (APtN) alters the antinociceptive effects of stimulating the retrosplenial cortex (RSC) in rats. MAIN METHOD: Changes in the nociceptive threshold were evaluated using the tail flick or incision pain tests in rats that were electrically stimulated at the RSC after the injection of saline, CoCl(2) (1 mM, 0.10 µL) or antagonists into the dorsal or ventral APtN. KEY FINDINGS: The injection of CoCl(2), naloxonazine (5 µg/0.10 µL) or methiothepin (3 µg/0.10 µL) into the dorsal APtN reduced the stimulation-produced antinociception from the RSC in the rat tail flick test. Reduction of incision pain was observed following stimulation of the RSC after the injection of the same substances into the ventral APtN. The injection of atropine (10 ng/0.10 µL) or ketanserine (5 µg/0.10 µL) into the dorsal or ventral APtN was ineffective against the antinociception resulting from RSC stimulation. SIGNIFICANCE: µ(1)-opioid- and 5-HT(1)-expressing neurons and cell processes in dorsal and ventral APtN are both implicated in the mediation of stimulation-produced antinociception from the RSC in the rat tail flick and incision pain tests, respectively.
Asunto(s)
Corteza Cerebral/metabolismo , Terapia por Estimulación Eléctrica/métodos , Manejo del Dolor/métodos , Receptores Opioides mu/metabolismo , Receptores de Serotonina 5-HT1/metabolismo , Animales , Atropina/farmacología , Cobalto/farmacología , Modelos Animales de Enfermedad , Masculino , Metiotepina/farmacología , Naloxona/análogos & derivados , Naloxona/farmacología , Umbral del Dolor , Ratas , Ratas Wistar , Receptores Opioides mu/efectos de los fármacos , Receptores de Serotonina 5-HT1/efectos de los fármacosRESUMEN
The mechanisms through which electro-acupuncture (EA) and tricyclic antidepressants produce analgesia seem to be complementary: EA inhibits the transmission of noxious messages by activating supraspinal serotonergic and noradrenergic neurons that project to the spinal cord, whereas tricyclic antidepressants affect pain transmission by inhibiting the reuptake of norepinephrine and serotonin at the spinal level. This study utilized the tail-flick test and a model of post-incision pain to compare the antihyperalgesic effects of EA at frequencies of 2 or 100 Hz in rats treated with intraperitoneal or intrathecal amitriptyline (a tricyclic antidepressant). A gradual increase in the tail-flick latency (TFL) occurred during a 20-min period of EA. A strong and long-lasting reduction in post-incision hyperalgesia was observed after stimulation; the effect after 2 Hz lasting longer than after 100-Hz EA. Intraperitoneal or intrathecal amitriptyline potentiated the increase in TFL in the early moments of 2- or 100-Hz EA, and the intensity of the antihyperalgesic effect of 100-Hz EA in both the incised and non-incised paw. In contrast, it did not significantly change the intensity of the antihyperalgesic effect of 2-Hz EA. The EA-induced antihyperalgesic effects lasted longer after intraperitoneal or intrathecal amitriptyline than after saline, with this effect of amitriptyline being more evident after 100- than after 2-Hz EA. The synergetic effect of amitriptyline and EA against post-incision pain shown here may therefore represent an alternative for prolonging the efficacy of EA in the management of post-surgical clinical pain.
Asunto(s)
Amitriptilina/uso terapéutico , Analgésicos no Narcóticos/uso terapéutico , Electroacupuntura/métodos , Hiperalgesia/terapia , Manejo del Dolor/métodos , Amitriptilina/farmacología , Analgésicos no Narcóticos/farmacología , Animales , Terapia Combinada , Hiperalgesia/tratamiento farmacológico , Masculino , Dimensión del Dolor , Umbral del Dolor/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
1. Train-of-four fade (TOF(fade) ) is a clinically useful parameter to monitor the degree of block of neuromuscular transmission in curarized patients. Experimentally, TOF(fade) has been attributed to the blockade of facilitatory nicotinic receptors on motor nerve terminals. There is less information regarding the involvement of coexistent presynaptic receptors (e.g. muscarinic M(1) and M(2) , adenosine A(1) and A(2A) ) in the TOF(fade) produced by antinicotinic agents. 2. In the present study, we evaluated the TOF(fade) caused by antinicotinic neuromuscular relaxants (hexamethonium, d-tubocurarine, vecuronium and rocuronium) as the ratio of the muscle tension produced in the rat diaphragm by the fourth to the first stimulus (T(4) /T(1) ) of a train-of-four stimuli delivered to the phrenic nerve trunk at a frequency of 2 Hz. 3. All antinicotinic agents, except hexamethonium, decreased the amplitude of muscle tension during the first stimulus. Hexamethonium, (5.47 mmol/L), d-tubocurarine- (1.1 µmol/L), vecuronium (4.7 µmol/L)- and rocuronium (9.8 µmol/L)-induced TOF(fade) was attenuated by 10 nmol/L pirenzepine (an M(1) receptor antagonist), 1 µmol/L methoctramine (an M(2) receptor antagonist) and 2.5 nmol/L 1,3-dipropyl-8-cyclopentylxanthine (an A(1) receptor antagonist). Blockade of the A(2A) receptor with 10 nmol/L ZM241385 partially reversed the TOF(fade) induced by d-tubocurarine, vecuronium and rocuronium, but not that caused by the 'pure' neuronal nicotinic receptor antagonist hexamethonium, unless one increased the concentration of ZM241385 to 50 nmol/L. 4. The data indicate that presynaptic M(1) , M(2) , A(1) and A(2A) receptors play a role in neuromuscular TOF(fade) caused by antinicotinic neuromuscular relaxants. Such interplay depends on adenosine tonus and on the affinity of neuromuscular blocking agents for neuronal versus muscular nicotinic receptors.
Asunto(s)
Bloqueantes Neuromusculares/farmacología , Antagonistas Nicotínicos/farmacología , Receptores Muscarínicos/metabolismo , Receptores Nicotínicos/metabolismo , Receptores Presinapticos/metabolismo , Receptores Purinérgicos P1/metabolismo , Periodo Refractario Electrofisiológico/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Animales , Diafragma/efectos de los fármacos , Estimulación Eléctrica/métodos , Masculino , Contracción Muscular/efectos de los fármacos , Nervio Frénico/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Sympathetic ganglion block (SGB) or intravenous regional block (IVRB) has been recommended for pain management in patients with complex regional pain syndrome type I (CRPS-I). Forty-five patients were initially selected but only 43 were accepted for the study. The present study evaluated the efficacy of IVRB produced by combining 70 mg lidocaine with 30 µg clonidine (14 patients, 1 male/13 females, age range: 27-50 years) versus SGB produced by the injection of 70 mg lidocaine alone (14 patients, 1 male/13 females, age range: 27-54 years) or combined with 30 µg clonidine (15 patients, 1 male/14 females, age range: 25-50 years) into the stellate ganglion for pain management in patients with upper extremity CRPS-I. Each procedure was repeated five times at 7-day intervals, and pain intensity and duration were measured using a visual analog scale immediately before each procedure. A progressive and significant reduction in pain scores and a significant increase in the duration of analgesia were observed in all groups following the first three blocks, but no further improvement was obtained following the last two blocks. Drowsiness, the most frequent side effect, and dry mouth occurred only in patients submitted to SGB with lidocaine combined with clonidine. The three methods were similar regarding changes in pain intensity and duration of analgesia. However, IVRB seems to be preferable to SGB due to its easier execution and lower risk of undesirable effects.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anestesia Intravenosa/métodos , Anestésicos Locales/administración & dosificación , Bloqueo Nervioso Autónomo/métodos , Clonidina/administración & dosificación , Lidocaína/administración & dosificación , Distrofia Simpática Refleja/tratamiento farmacológico , Anestésicos Locales/efectos adversos , Clonidina/efectos adversos , Ganglios Simpáticos , Lidocaína/efectos adversos , Dimensión del Dolor , Factores de Tiempo , Resultado del TratamientoRESUMEN
Sympathetic ganglion block (SGB) or intravenous regional block (IVRB) has been recommended for pain management in patients with complex regional pain syndrome type I (CRPS-I). Forty-five patients were initially selected but only 43 were accepted for the study. The present study evaluated the efficacy of IVRB produced by combining 70 mg lidocaine with 30 µg clonidine (14 patients, 1 male/13 females, age range: 27-50 years) versus SGB produced by the injection of 70 mg lidocaine alone (14 patients, 1 male/13 females, age range: 27-54 years) or combined with 30 µg clonidine (15 patients, 1 male/14 females, age range: 25-50 years) into the stellate ganglion for pain management in patients with upper extremity CRPS-I. Each procedure was repeated five times at 7-day intervals, and pain intensity and duration were measured using a visual analog scale immediately before each procedure. A progressive and significant reduction in pain scores and a significant increase in the duration of analgesia were observed in all groups following the first three blocks, but no further improvement was obtained following the last two blocks. Drowsiness, the most frequent side effect, and dry mouth occurred only in patients submitted to SGB with lidocaine combined with clonidine. The three methods were similar regarding changes in pain intensity and duration of analgesia. However, IVRB seems to be preferable to SGB due to its easier execution and lower risk of undesirable effects.
Asunto(s)
Anestesia Intravenosa/métodos , Anestésicos Locales/administración & dosificación , Bloqueo Nervioso Autónomo/métodos , Clonidina/administración & dosificación , Lidocaína/administración & dosificación , Distrofia Simpática Refleja/tratamiento farmacológico , Adulto , Anestésicos Locales/efectos adversos , Clonidina/efectos adversos , Femenino , Ganglios Simpáticos , Humanos , Lidocaína/efectos adversos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Factores de Tiempo , Resultado del TratamientoRESUMEN
Endogenous angiotensin (Ang) II and/or an Ang II-derived peptide, acting on Ang type 1 (AT(1)) and Ang type 2 (AT(2)) receptors, can carry out part of the nociceptive control modulated by periaqueductal gray matter (PAG). However, neither the identity of this putative Ang-peptide, nor its relationship to Ang II antinociceptive activity was clarified. Therefore, we have used tail-flick and incision allodynia models combined with an HPLC time course of Ang metabolism, to study the Ang III antinociceptive effect in the rat ventrolateral (vl) PAG using peptidase inhibitors and receptor antagonists. Ang III injection into the vlPAG increased tail-flick latency, which was fully blocked by Losartan and CGP 42,112A, but not by divalinal-Ang IV, indicating that Ang III effect was mediated by AT(1) and AT(2) receptors, but not by the AT(4) receptor. Ang III injected into the vlPAG reduced incision allodynia. Incubation of Ang II with punches of vlPAG homogenate formed Ang III, Ang (1-7) and Ang IV. Amastatin (AM) inhibited the formation of Ang III from Ang II by homogenate, and blocked the antinociceptive activity of Ang II injection into vlPAG, suggesting that aminopeptidase A (APA) formed Ang III from Ang II. Ang III can also be formed from Ang I by a vlPAG alternative pathway. Therefore, the present work shows, for the first time, that: (i) Ang III, acting on AT(1) and AT(2) receptors, can elicit vlPAG-mediated antinociception, (ii) the conversion of Ang II to Ang III in the vlPAG is required to elicit antinociception, and (iii) the antinociceptive activity of endogenous Ang II in vlPAG can be ascribed preponderantly to Ang III.
Asunto(s)
Analgésicos/farmacología , Angiotensina III/metabolismo , Nociceptores/efectos de los fármacos , Dolor/metabolismo , Sustancia Gris Periacueductal/metabolismo , Analgésicos/metabolismo , Angiotensina II/farmacología , Angiotensina III/farmacología , Antagonistas de Receptores de Angiotensina , Animales , Modelos Animales de Enfermedad , Interacciones Farmacológicas/fisiología , Vías Eferentes/efectos de los fármacos , Vías Eferentes/metabolismo , Glutamil Aminopeptidasa/biosíntesis , Losartán/farmacología , Masculino , Microinyecciones , Inhibición Neural/efectos de los fármacos , Inhibición Neural/fisiología , Nociceptores/metabolismo , Oligopéptidos/farmacología , Dolor/tratamiento farmacológico , Dolor/fisiopatología , Dimensión del Dolor , Umbral del Dolor/efectos de los fármacos , Umbral del Dolor/fisiología , Péptidos/farmacología , Sustancia Gris Periacueductal/efectos de los fármacos , Ratas , Ratas Wistar , Receptores de Angiotensina/metabolismoRESUMEN
1. Cholinergic agonists and acetylcholinesterase inhibitors, such as neostigmine, produce a muscarinic receptor-mediated antinociception in several animal species that depends on activation of spinal cholinergic neurons. However, neostigmine causes antinociception in sheep only in the early, and not late, postoperative period. 2. In the present study, a model of postoperative pain was used to determine the antinociceptive effects of bethanechol (a muscarinic agonist) and neostigmine administered intrathecally 2, 24 or 48 h after a plantar incision in a rat hind paw. Changes in the threshold to punctate mechanical stimuli were evaluated using an automated electronic von Frey apparatus. 3. Mechanical hyperalgesia was obtained following plantar incision, the effect being stronger during the immediate (2 h) than the late post-surgical period. Bethanechol (15-90 microg/5 microL) or neostigmine (1-3 microg/5 microL) reduced incision-induced mechanical hyperalgesia, the effects of both drugs being more intense during the immediate (2 h) than the late post-surgical period. 4. The ED(50) for bethanechol injected at 2, 24 and 48 h was 5.6, 51.9 and 82.5 microg/5 microL, respectively. The corresponding ED(50) for neostigmine was 1.62, 3.02 and 3.8 microg/5 microL, respectively. 5. The decline in the antinociceptive potency of neostigmine with postoperative time is interpreted as resulting from a reduction in pain-induced activation of acetylcholine-releasing descending pathways. However, the similar behaviour of bethanechol in the same model points to an additional mechanism involving intrinsic changes in spinal muscarinic receptors.