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1.
J Clin Neurosci ; 98: 1-5, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35114475

RESUMO

An abnormal or absent superficial abdominal reflex (SAR) may be associated with an underlying spinal cord syrinx. The sensitivity of an abnormal or absent SAR and the relationship to Chiari malformation type I (CM-I) or syrinx morphology has not been studied. We aimed to describe the relationship between SAR abnormalities and syrinx size, location, and etiology. Children who underwent brain or c-spine MRI over 11 years were reviewed in this retrospective cohort study. Patients with idiopathic and CM-I-associated syringes (axial diameter ≥ 3 mm) were included. Clinical examination findings (including SAR) and imaging characteristics were analyzed. Of 271 patients with spinal cord syrinx, 200 had either CM-I-associated or idiopathic syrinx, and 128 of these patients had SAR-evaluation documentation. Forty-eight percent (62/128) had an abnormal or absent reflex. Abnormal/absent SAR was more common in patients with CM-I-associated syrinx (61%) compared with idiopathic syrinx (22%) (P < 0.0001). Abnormal/absent SAR was associated with wider syringes (P < 0.001), longer syringes (P < 0.05), and a more cranial location of the syrinx (P < 0.0001). Controlling for CM-I, scoliosis, age, sex, cranial extent of syrinx, and syrinx dimensions, CM-I was independently associated with abnormal or absent SAR (OR 4.2, 95% CI 1.4-14, P < 0.01). Finally, the sensitivity of SAR for identifying a patient with syrinx was 48.1%. An abnormal/absent SAR was present in most patients with CM-I-associated syrinx but in a minority of patients with idiopathic syrinx. This has implications for pathophysiology of CM-I-associated syrinx and in guiding clinical care of patients presenting with syrinx.


Assuntos
Malformação de Arnold-Chiari , Escoliose , Siringomielia , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/diagnóstico por imagem , Criança , Humanos , Imageamento por Ressonância Magnética/efeitos adversos , Reflexo Abdominal/fisiologia , Reflexo Anormal , Estudos Retrospectivos , Escoliose/etiologia , Siringomielia/complicações , Siringomielia/diagnóstico por imagem
4.
Respir Care ; 62(12): 1571-1581, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28900040

RESUMO

BACKGROUND: Diaphragm excursion is limited during respiratory maneuvers after a stroke. How the diaphragm is limited during reflexive coughs and affects the effectiveness of cough in stroke patients is unclear. This study aimed to measure reflexive cough strength by cough peak flow (CPF) induced by citric acid nebulization (2.8 mol/L), record diaphragm excursions during reflexive coughs in stroke subjects at risk of silent aspiration, and compare these values with those of stroke subjects without risk of aspiration or dysphagia. METHODS: Twenty-one subjects with subacute stroke (mean stroke onset, 13.6 d) at risk of silent aspiration (penetration-aspiration scale, 8) and 21 stroke subjects without dysphagia or aspiration (controls) were included. Diaphragmatic excursions were assessed using real-time sonography in all subjects; the main outcome measure was reflexive CPF induced by citric acid nebulization. RESULTS: The median (interquartile range) values of citric acid-induced CPF values were significantly more reduced in the 21 subjects with silent aspiration (45 [0-83] L/min) than in the control subjects (97 [66-162] L/min) (P = .004). Diaphragmatic excursions during the reflexive coughs were also significantly reduced (P < .001), although both groups had a similar range in the initial National Institutes of Health Stroke Scale scores and level of disability, as measured by the modified Barthel index. Citric acid-induced CPF was significantly correlated with the number of generated coughs (rs = 0.69), voluntary cough CPF (rs = 0.85), and degree of diaphragm excursion on both sides (rs = 0.50 [hemiplegic] and rs = 0.55 [nonhemiplegic]) but not correlated with the degree of hemiparesis, National Institutes of Health Stroke Scale score, or modified Barthel index scores. The 6-month follow up revealed that 7 subjects in group A experienced aspiration pneumonia. CONCLUSIONS: Stroke subjects at risk of silent aspiration showed reduced CPF and more limited diaphragm excursion during the citric acid-induced reflexive cough test. (ClinicalTrials.gov registration NCT02080988.).


Assuntos
Ácido Cítrico/administração & dosagem , Tosse/fisiopatologia , Diafragma/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Administração por Inalação , Idoso , Estudos de Casos e Controles , Tosse/induzido quimicamente , Transtornos de Deglutição/etiologia , Diafragma/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Pico do Fluxo Expiratório , Pneumonia Aspirativa/etiologia , Reflexo Abdominal , Medição de Risco/métodos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações , Ultrassonografia
5.
J. coloproctol. (Rio J., Impr.) ; 37(2): 88-94, Apr.-June 2017. graf
Artigo em Inglês | LILACS | ID: biblio-893978

RESUMO

ABSTRACT Objective: The aim of this study was to investigate the effects of acute physical and psychological stress and temporary central nucleus of the amygdala (CeA) block on stress-induced visceral hypersensitivity. Methods: Forty two male Wistar rats were used in this study. Animals were divided into 7 groups (n = 6); 1 - Control, 2 - physical stress, 3 - psychological stress, 4 - sham, 5 - lidocaine, 6 - lidocaine + physical stress and 7 - lidocaine + psychological stress. Stress induction was done using a communication box. Results: Abdominal withdrawal reflex (AWR) score was monitored one hour after stress exposure. AWR score significantly heightened at 20, 40 and 60 mmHg in the psychological stress group compared with control (p < 0.05), while, it was almost unchanged in other groups. This score was strikingly decreased at 20, 40 and 60 mmHg in lidocaine + psychological stress group compared with psychological stress with no tangible response on physical stress. Total stool weight was significantly increased in psychological stress group compared with control (0.72 ± 0.15, 0.1 ± 0.06 g) (p < 0.05), but it did not change in physical stress compared to control group (0.16 ± 0.12, 0.1 ± 0.06 g) (p < 0.05). Concomitant use of lidocaine with stress followed the same results in psychological groups (0.18 ± 0.2, 0.72 ± 0.15 g) (p < 0.05), while it did not have any effect on physical stress group (0.25 ± 0.1, 0.16 ± 0.12 g) (p < 0.05). Conclusions: Psychological stress could strongly affect visceral hypersensitivity. This effect is statistically comparable with physical stress. Temporary CeA block could also reduce visceral hypersensitivity post-acute psychological stress.


RESUMEN Objetivo: O objetivo desse estudo foi investigar os efeitos do estresse físico e psicológico agudo e bloqueio temporário do núcleo central da amídala (CeA) na hipersensibilidade visceral induzida por estresse. Métodos: Quarenta e dois ratos Wistar machos foram empregados nesse estudo. Os animais foram divididos em 7 grupos (n = 6): 1 - Controle, 2 - estresse físico, 3 - estresse psicológico, 4 - simulacro, 5 - lidocaína, 6 - lidocaína + estresse físico e 7 - lidocaína + estresse psicológico. A indução do estresse foi feita com o uso de uma caixa de comunicação. Resultados: O escore do reflexo de retirada abdominal (RRA) foi monitorado uma hora depois da exposição ao estresse. O escore RRA aumentou significativamente a 20, 40 e 60 mmHg no grupo de estresse psicológico versus controle (p < 0,05), enquanto que praticamente permaneceu inalterado nos demais grupos. Esse escore diminuiu drasticamente a 20, 40 e 60 mmHg no grupo de lidocaína + estresse psicológico versus estresse psicológico, sem resposta tangível no estresse físico. O peso total das fezes aumentou significativamente no grupo de estresse psicológico versus controle (0,72 ± 0,15, 0,1 ± 0,06 g) (p < 0,05), mas não houve mudança no grupo de estresse físico versus controle (0,16 ± 0,12, 0,1 ± 0,06 g) (p < 0,05). O uso simultâneo da lidocaína com o estresse acompanhou os mesmos resultados nos grupos psicológicos (0,18 ± 0,2, 0,72 ± 0,15 g) (p < 0,05), enquanto que não foi observado qualquer efeito no grupo de estresse físico (0,25 ± 0,1, 0,16 ± 0,12 g) (p < 0,05). Conclusões: O estresse psicológico pode afetar fortemente a hipersensibilidade visceral. Esse efeito é estatisticamente comparável com o estresse físico. Um bloqueio temporário do CeA também pode reduzir a hipersensibilidade visceral pós-estresse psicológico agudo.


Assuntos
Animais , Ratos , Estresse Psicológico/complicações , Vísceras/fisiopatologia , Núcleo Central da Amígdala/fisiopatologia , Hipersensibilidade/fisiopatologia , Reflexo Abdominal/fisiologia , Ratos Wistar , Percepção da Dor/fisiologia , Núcleo Central da Amígdala/metabolismo
6.
World J Gastroenterol ; 22(22): 5211-27, 2016 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-27298564

RESUMO

AIM: To evaluate gut microbial dysbiosis in two visceral hypersensitive models in comparison with irritable bowel syndrome (IBS) patients and to explore the extent to which these models capture the dysbiosis of IBS patients. METHODS: Visceral hypersensitivity was developed using the maternal separation (MS) rat model and post-inflammatory rat model. The visceral sensitivity of the model groups and control group was evaluated using the abdominal withdraw reflex score and electromyography in response to graded colorectal distention. The 16S ribosomal RNA gene from fecal samples was pyrosequenced and analyzed. The correlation between dysbiosis in the microbiota and visceral hypersensitivity was calculated. Positive findings were compared to sequencing data from a published human IBS cohort. RESULTS: Dysbiosis triggered by neonatal maternal separation was lasting but not static. Both MS and post-inflammatory rat fecal microbiota deviated from that of the control rats to an extent that was larger than the co-housing effect. Two short chain fatty acid producing genera, Fusobacterium and Clostridium XI, were shared by the human IBS cohort and by the maternal separation rats and post-inflammatory rats, respectively, to different extents. Fusobacterium was significantly increased in the MS group, and its abundance positively correlated with the degree of visceral hypersensitivity. Porphyromonadaceae was a protective biomarker for both the rat control group and healthy human controls. CONCLUSION: The dysbiosis MS rat model and the post-inflammatory rat model captured some of the dysbiosis features of IBS patients. Fusobacterium, Clostridium XI and Porphyromonadaceae were identified as targets for future mechanistic research.


Assuntos
Colo/inervação , Disbiose , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Hiperalgesia/microbiologia , Síndrome do Intestino Irritável/microbiologia , Animais , Clostridium/classificação , Modelos Animais de Doenças , Eletromiografia , Fezes/microbiologia , Fusobactérias/classificação , Humanos , Hiperalgesia/fisiopatologia , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/fisiopatologia , Mecanotransdução Celular , Percepção da Dor , Filogenia , Pressão , Ratos Sprague-Dawley , Reto/inervação , Reflexo Abdominal , Reflexo Anormal , Ribotipagem
7.
J Biomech ; 49(6): 933-938, 2016 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-26518368

RESUMO

Reflex activity of the lower leg muscles involved when compensating for falls has already been thoroughly investigated. However, the trunk׳s role in this compensation strategy remains unclear. The purpose of this study, therefore, was to analyze the kinematics and muscle activity of the trunk during perturbed walking. Ten subjects (29 ± 3 yr;79 ± 11 cm;74 ± 14 kg) walked (1m/s) on a split-belt treadmill, while 5 randomly timed, right-sided perturbations (treadmill belt deceleration: 40 m/s(2)) were applied. Trunk muscle activity was assessed with a 12-lead-EMG. Trunk kinematics were measured with a 3D-motion analysis system (12 markers framing 3 segments: upper thoracic area (UTA), lower thoracic area (LTA), lumbar area (LA)). The EMG-RMS [%] (0-200 ms after perturbation) was analyzed and then normalized to the RMS of normal walking. The total range of motion (ROM;[°]) for the extension/flexion, lateral flexion and rotation of each segment were calculated. Individual kinematic differences between walking and stumbling [%; ROM] were also computed. Data analysis was conducted descriptively, followed by one- and two-way ANOVAs (α=0.05). Stumbling led to an increase in ROM, compared to unperturbed gait, in all segments and planes. These increases ranged between 107 ± 26% (UTA/rotation) and 262 ± 132% (UTS/lateral flexion), significant only in lateral flexion. EMG activity of the trunk was increased during stumbling (abdominal: 665 ± 283%; back: 501 ± 215%), without significant differences between muscles. Provoked stumbling leads to a measurable effect on the trunk, quantifiable by an increase in ROM and EMG activity, compared to normal walking. Greater abdominal muscle activity and ROM of lateral flexion may indicate a specific compensation pattern occurring during stumbling.


Assuntos
Acidentes por Quedas/prevenção & controle , Caminhada/fisiologia , Adulto , Dorso/fisiologia , Fenômenos Biomecânicos , Feminino , Marcha/fisiologia , Humanos , Masculino , Músculo Esquelético/fisiologia , Projetos Piloto , Equilíbrio Postural , Desempenho Psicomotor , Amplitude de Movimento Articular/fisiologia , Reflexo Abdominal
10.
J Neurol ; 261(12): 2264-74, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24695995

RESUMO

In the late 1800s, Wilhelm Erb, Joseph Babinski, William Gowers, and others helped develop the neurologic examination as we know it today. Erb was one of the first to emphasize a detailed and systematic neurologic exam and was co-discoverer of the muscle stretch reflex, Gowers began studying the knee jerk shortly after it was described, and Babinski focused on finding reliable signs that could differentiate organic from hysterical paralysis. These physicians and others emphasized the bedside examination of reflexes, which have been an important part of the neurologic examination ever since. This review will focus on the history of the examination of the following muscle stretch and superficial/cutaneous reflexes: knee jerk, jaw jerk, deep abdominal reflexes, superficial abdominal reflexes, plantar reflex/Babinski sign, and palmomental reflex. The history of reflex grading will also be discussed.


Assuntos
Exame Neurológico/história , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Reflexo/fisiologia , Reflexo Abdominal/fisiologia , Reflexo Anormal/fisiologia , Reflexo de Babinski/fisiologia , Reflexo de Estiramento/fisiologia
11.
Am J Physiol Gastrointest Liver Physiol ; 304(9): G763-72, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23449670

RESUMO

The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood, and treatment remains difficult. We have previously reported that colon-specific dorsal root ganglion (DRG) neurons were hyperactive in a rat model of IBS induced by neonatal colonic inflammation (NCI). This study was designed to examine plasticity of voltage-gated Na(+) channel activities and roles for the endogenous hydrogen sulfide-producing enzyme cystathionine ß-synthetase (CBS) in chronic visceral hyperalgesia. Abdominal withdrawal reflex (AWR) scores were recorded in response to graded colorectal distention in adult male rats as a measure of visceral hypersensitivity. Colon-specific DRG neurons were labeled with 1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate and acutely dissociated for measuring Na(+) channel currents. Western blot analysis was employed to detect changes in expressions of voltage-gated Na(+) (Na(V)) channel subtype 1.7, Na(V)1.8, and CBS. NCI significantly increased AWR scores when compared with age-matched controls. NCI also led to an ~2.5-fold increase in Na(+) current density in colon-specific DRG neurons. Furthermore, NCI dramatically enhanced expression of Na(V)1.7, Na(V)1.8, and CBS in colon-related DRGs. CBS was colocalized with Na(V)1.7 or -1.8 in colon-specific DRG neurons. Administration of O-(carboxymethyl)hydroxylamine hemihydrochloride (AOAA), an inhibitor for CBS, remarkably suppressed Na(+) current density and reduced expression of Na(V)1.7 and Na(V)1.8. More importantly, intraperitoneal or intrathecal application of AOAA attenuated AWR scores in NCI rats in a dose-dependent manner. These data suggest that NCI enhances Na(+) channel activity of colon DRG neurons, which is most likely mediated by upregulation of CBS expression, thus identifying a potential target for treatment for chronic visceral pain in patients with IBS.


Assuntos
Colite/fisiopatologia , Cistationina beta-Sintase/biossíntese , Gânglios Espinais/fisiologia , Canal de Sódio Disparado por Voltagem NAV1.7/fisiologia , Canal de Sódio Disparado por Voltagem NAV1.8/fisiologia , Ácido Acético , Ácido Amino-Oxiacético/farmacologia , Animais , Animais Recém-Nascidos , Carbocianinas , Colite/induzido quimicamente , Corantes , Cistationina beta-Sintase/antagonistas & inibidores , Hiperalgesia/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Canal de Sódio Disparado por Voltagem NAV1.7/biossíntese , Canal de Sódio Disparado por Voltagem NAV1.8/biossíntese , Ratos , Ratos Sprague-Dawley , Reflexo Abdominal/efeitos dos fármacos
12.
Am J Physiol Gastrointest Liver Physiol ; 304(4): G311-21, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-23139220

RESUMO

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain in association with altered bowel movements. The underlying mechanisms of visceral hypersensitivity remain elusive. This study was designed to examine the role for sodium channels in a rat model of chronic visceral hyperalgesia induced by neonatal maternal deprivation (NMD). Abdominal withdrawal reflex (AWR) scores were performed on adult male rats. Colon-specific dorsal root ganglion (DRG) neurons were labeled with DiI and acutely dissociated for measuring excitability and sodium channel current under whole-cell patch-clamp configurations. The expression of Na(V)1.8 was analyzed by Western blot and quantitative real-time PCR. NMD significantly increased AWR scores, which lasted for ~6 wk in an association with hyperexcitability of colon DRG neurons. TTX-resistant but not TTX-sensitive sodium current density was greatly enhanced in colon DRG neurons in NMD rats. Compared with controls, activation curves showed a leftward shift in NMD rats whereas inactivation curves did not differ significantly. NMD markedly accelerated the activation time of peak current amplitude without any changes in inactivation time. Furthermore, NMD remarkably enhanced expression of Na(V)1.8 at protein levels but not at mRNA levels in colon-related DRGs. The expression of Na(V)1.9 was not altered after NMD. These data suggest that NMD enhances TTX-resistant sodium activity of colon DRG neurons, which is most likely mediated by a leftward shift of activation curve and by enhanced expression of Na(V)1.8 at protein levels, thus identifying a specific molecular mechanism underlying chronic visceral pain and sensitization in patients with IBS.


Assuntos
Colo/metabolismo , Gânglios Espinais/fisiologia , Privação Materna , Canal de Sódio Disparado por Voltagem NAV1.8/biossíntese , Animais , Hiperalgesia , Síndrome do Intestino Irritável , Masculino , Canal de Sódio Disparado por Voltagem NAV1.8/efeitos dos fármacos , Canal de Sódio Disparado por Voltagem NAV1.8/fisiologia , Neurônios/metabolismo , Ratos , Reflexo Abdominal , Tetrodotoxina/farmacologia
13.
J Assoc Physicians India ; 61(3): 168-72, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24475678

RESUMO

OBJECTIVES: To study clinical presentation, hospital care and outcome of patients of Guillain Barre Syndrome (GBS) and number of patients of respiratory failure and need for ventilators. To study efficacy of IVIg in patients of GBS. MATERIAL AND METHODS: 40 patients of GBS studied in detail including history, clinical examination and investigations (Nerve conduction velocity and C.S.F. examination). All patients were watched for respiratory insufficiency and those who developed respiratory paralysis were given assisted mechanical ventilation. Patients were treated with IVIG and outcome was observed. Outcome of 2 groups of patients one treated with IVIg and other not treated with IVIg (supportive line of treatment) were compared. RESULTS: Commonest age group affected was 13-40 yrs. The male:female ratio was 1.5:1. Antecedent infection in form of fever, cough [11 patients], loose motions [10 patients] were present in 21 out of 40 patients. Quadriparesis was present in 39 patients and paraparesis in 1 patient. Cranial nerve involvement was seen in 25 out of 40 patients. Facial nerve was involved in 12 [30%] patients and Glossopharyengeal, vagus nerves were involved in 12 [30%] patients. Areflexia was found in all 40 patients. In CSF examination, albuminocytologic dissociation was present in 17 out of 26 patients. NCV findings show conduction velocity slowing, delayed f latencies in 90% patients. Out of 40 patients, 13 [30%] required mechanical ventilation. Out of 40 patients, 14 were treated with IVIg, 4 patients treated with plasmapheresis and 22 patients received only supportive treatment. Out of 40 patients 30 [75%] patients recovered completely, 8 [20%] patients died and 2 [5%] patients developed severe neurologic deficit. CONCLUSION: GBS is more common in 13-40 yrs age group with male:female ratio of 1.5:1. Antecedent infection is seen in 55% patients. Commonest presentation was paresthesia in legs and ascending paralysis. One third [32.5%] patients developed respiratory paralysis and needed ventilatory support. Patients who received IVIg early in the course of disease had faster recovery as compared to patients who received only supportive line of treatment.


Assuntos
Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/terapia , Adolescente , Adulto , Idoso , Nervos Cranianos/fisiopatologia , Feminino , Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Plasmaferese , Quadriplegia/etiologia , Reflexo Abdominal , Respiração Artificial , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Adulto Jovem
14.
J Neurosci Res ; 90(12): 2328-34, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22930524

RESUMO

The mechanism underlying visceral pain is still largely unclear. Recently, much attention has focused on a potential modulatory role of brain-derived neurotrophic factor (BDNF) in visceral pain. In the present study, we investigated the expression of BDNF in dorsal root ganglia (DRG) primary sensory neurons and its role in a colorectal distention (CRD)-induced model of visceral pain. Results obtained from enzyme-linked immunosorbant assay (ELISA) revealed that BDNF protein was upregulated after CRD. An abdominal withdrawal reflex (AWR) assay confirmed that BDNF played an antinociceptive role in this model. Application of BDNF directly to DRG neurons decreased their hypersensitivity when evoked by CRD. Pretreatment with k252a partially blocked the effect of BDNF. These findings suggest that BDNF might be a novel analgesic agent for the treatment of visceral pain.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/fisiologia , Gânglios Espinais/fisiopatologia , Hiperalgesia/fisiopatologia , Células Receptoras Sensoriais/fisiologia , Dor Visceral/fisiopatologia , Animais , Fator Neurotrófico Derivado do Encéfalo/antagonistas & inibidores , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Fator Neurotrófico Derivado do Encéfalo/genética , Carbazóis/farmacologia , Células Cultivadas , Dilatação Patológica/complicações , Dilatação Patológica/fisiopatologia , Regulação da Expressão Gênica , Alcaloides Indólicos/farmacologia , Masculino , Nociceptores/fisiologia , Medição da Dor , Técnicas de Patch-Clamp , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Reflexo Abdominal/fisiologia , Método Simples-Cego
16.
PLoS One ; 7(12): e53165, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23285261

RESUMO

BACKGROUND: Hydrogen sulfide (H2S) functions as a neuromodulator, but whether it modulates visceral pain is not well known. This study was designed to determine the role for the endogenous H2S producing enzyme cystathionine ß-synthetase (CBS) and cystathionine γ-lyase (CSE) in a validated rat model of visceral hyperalgesia (VH). METHODS: VH was induced by nine-day heterotypic intermittent stress (HIS). Abdominal withdrawal reflex (AWR) scores were determined by measuring the visceromoter responses to colorectal distension (CRD). Dorsal root ganglia (DRG) neurons innervating the colon were labeled by injection of DiI (1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate) into the colon wall. Patch clamp recording techniques were employed to examine excitability and sodium channel currents of colon specific DRG neurons. Tissues from colon related thoracolumbar DRGs were analyzed for CBS, CSE and sodium channel expression. RESULTS: HIS significantly increased the visceromotor responses to CRD in association with an upregulated expression of CBS not CSE proteins in colon related DRGs. Administration of O-(Carboxymethyl)hydroxylamine hemihydrochloride (AOAA), an inhibitor of CBS, attenuated the AWR scores in HIS-treated rats, in a dose dependent fashion. In contrast, AOAA did not produce any effect on AWR scores in healthy control rats. AOAA reversed the potentiation of sodium channel current densities of colon specific DRG neurons of HIS rats. To further confirm the role for CBS-H2S signaling, NaHS was used to mimic the production of H2S by CBS. Application of NaHS significantly enhanced neuronal excitability and potentiated sodium channel current densities of colon DRG neurons from healthy control rats. Furthermore, AOAA reversed the upregulation of Na(V)1.7 and Na(V)1.8 in colon related DRGs of HIS rats. CONCLUSION: Our results suggest that upregulation of CBS expression might play an important role in developing VH via sensitization of sodium channels in peripheral nociceptors, thus identifying a specific neurobiological target for the treatment of VH in functional bowel syndromes.


Assuntos
Cistationina beta-Sintase/metabolismo , Hiperalgesia/enzimologia , Estresse Psicológico/fisiopatologia , Dor Visceral/enzimologia , Animais , Cistationina beta-Sintase/antagonistas & inibidores , Cistationina beta-Sintase/fisiologia , Inibidores Enzimáticos/farmacologia , Sulfeto de Hidrogênio/efeitos adversos , Sulfeto de Hidrogênio/metabolismo , Hiperalgesia/genética , Enteropatias/enzimologia , Enteropatias/etiologia , Enteropatias/genética , Masculino , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Reflexo Abdominal/efeitos dos fármacos , Estresse Psicológico/genética , Sulfetos/farmacologia , Tacrolimo/análogos & derivados , Tacrolimo/farmacologia , Regulação para Cima/fisiologia , Vísceras/metabolismo , Vísceras/patologia , Dor Visceral/etiologia
17.
Am J Gastroenterol ; 107(4): 597-603, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22085820

RESUMO

OBJECTIVES: Systemic sclerosis (SSc) is a chronic multi-system autoimmune disorder with gastrointestinal tract (GIT) involvement in up to 90% of patients and anorectal involvement occurs in up to 50% of patients. The pathogenesis of gastrointestinal abnormalities may be both myogenic and neurogenic. We aimed to identify which anorectal physiological abnormalities correlate with clinical symptoms and thus understand the pathophysiology of anorectal involvement in SSc. METHODS: In total, 44 SSc patients (24 symptomatic (Sx) (fecal incontinence) and 20 asymptomatic (ASx)) and 20 incontinent controls (ICs) were studied. Patients underwent anorectal manometry, rectal mucosal blood flow (RMBF), rectal compliance (barostat), and rectoanal inhibitory reflex assessment (RAIR). RESULTS: Anal squeeze pressure was lower in the IC group compared with both the ASx and Sx groups (IC: 46.95 (30-63.9)) vs. ASx: 104.6 (81-128.3) vs. (Sx: 121.4 (101.3-141.6); P < 0.05). Resting pressure was lower in the IC group. RMBF and rectal compliance did not differ between groups. Anal, but not rectal, sensory threshold, was significantly attenuated in Sx patients (Sx: 10.4 (8.8-11.4) vs. ASx: 6.7 (5.7-7.7) vs. IC: 8.5 (6.5-10.4); P < 0.05). There was a positive correlation between anal sensory thresholds and incontinence score in SSc patients (r = 0.54; P < 0.05). RAIR was absent in 11/24 Sx patients but only in 2/20 ASx and in 1/20 IC patients. CONCLUSIONS: Fecal incontinence in SSc is related to neuropathy as suggested by absent RAIR and higher anal sensory threshold and is related less so to sphincter atrophy and rectal fibrosis.


Assuntos
Canal Anal/fisiopatologia , Incontinência Fecal/etiologia , Incontinência Fecal/fisiopatologia , Reto/fisiopatologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/fisiopatologia , Idoso , Análise de Variância , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Pressão , Reflexo Abdominal/fisiologia , Fluxo Sanguíneo Regional , Limiar Sensorial , Estatísticas não Paramétricas
18.
Dig Dis Sci ; 57(4): 865-72, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22160634

RESUMO

BACKGROUND: According to a recent study, vesicular glutamate transporter-3 (VGLUT3) contributes to injury-induced mechanical hyperalgesia in mice. AIMS: The aims of the study were to investigate whether VGLUT3 is involved in visceral pain, and whether transient intestinal infection or acute cold restraint stress (ACRS) affects VGLUT3 expression levels in rats. METHODS: Changes in VGLUT3 and c-Fos proteins were evaluated in rats which received noxious colorectal distension (CRD) stimulation. Transient intestinal infection was effected by oral administration of Trichinella spiralis (T. spiralis) larvae in Brown Norway rats. On the 100th day post-infection (PI), half of the PI-rats and non infected controls were subjected to an ACRS procedure. The visceromotor response to CRD was measured using the abdominal withdrawal reflex (AWR) score. Immunofluorescence and western blot analysis were used to estimate the expression of VGLUT3 in both peripheral and central neurons. RESULTS: Noxious stimulation induced a significant increase in the expression of VGLUT3 in the L6S1 spinal dorsal horn. Compared with the control group, the pain threshold was significantly decreased in the ACRS, PI, and PI + ACRS groups. VGLUT3 expression in the L6S1 dorsal root ganglion (DRG) and spinal neurons were significantly increased in PI and PI + ACRS groups as compared with the control group. CONCLUSIONS: VGLUT3 is involved in conduction of visceral pain sensation and in visceral hyperalgesia induced by Trichinella spiralis infection in rats.


Assuntos
Hiperalgesia/metabolismo , Trichinella spiralis , Triquinelose/complicações , Proteínas Vesiculares de Transporte de Glutamato/metabolismo , Dor Visceral/etiologia , Animais , Western Blotting , Colo/fisiopatologia , Dilatação Patológica , Hiperalgesia/etiologia , Hiperalgesia/fisiopatologia , Imuno-Histoquímica , Masculino , Limiar da Dor , Células do Corno Posterior/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Endogâmicos BN , Reflexo Abdominal , Medula Espinal/metabolismo , Proteínas Vesiculares de Transporte de Glutamato/fisiologia , Dor Visceral/metabolismo , Dor Visceral/fisiopatologia
19.
J Gastroenterol Hepatol ; 27(5): 935-44, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22141367

RESUMO

BACKGROUND AND AIM: Postinfectious irritable bowel syndrome (PI-IBS), which results from inflammation has been emphasized a lot recently. Dendritic cells (DCs) may contribute to intestinal mucosal immune activation in the pathogenesis of PI-IBS. This study tested the hypothesis that phenotype and function of intestinal lamina propria DCs (LPDCs) changed in the development of a PI-IBS mouse model. METHODS: Mice infected with Trichinella spiralis underwent abdominal withdrawal reflex (AWR) to evaluate visceral sensitivity. LPDCs were isolated and purified by intestine digestion and magnetic label-based technique. Surface markers were analyzed by flow cytometry. Endocytic activity, mixed lymphocyte reaction (MLR) and chemotaxis were studied. Cytokine production of the LPDCs cocultured with CD4(+) T cells was determined. RESULTS: Intestinal inflammation resolved after 8 weeks infection with sustained visceral hyperalgesia. Surface markers CD86 and MHCII were lower in the acute infection group, but increased in the PI-IBS stage. Enhanced ability of endocytic activity and decreased abilities to attract and stimulate CD4(+) T cell proliferation were in the acute infection group. However, LPDCs in the PI-IBS stage showed weakened endocytic ability with enhanced abilities to attract and stimulate CD4(+) T cell proliferation. Cocultured LPDCs with CD4(+) T cells showed a predominant Th2 response in the acute infection stage, and more important roles of Th1, Th17 responses in the PI-IBS stage. CONCLUSIONS: The hypothesis was supported that the phenotype and function of LPDCs changed in the development of PI-IBS, which induced the maintenance of intestinal mucosal immune activation and might provide a clue for the treatment of the disease.


Assuntos
Citocinas/metabolismo , Células Dendríticas/imunologia , Síndrome do Intestino Irritável/imunologia , Trichinella spiralis , Triquinelose/imunologia , Animais , Antígeno B7-2/metabolismo , Linfócitos T CD4-Positivos/fisiologia , Proliferação de Células , Células Cultivadas , Quimiotaxia , Células Dendríticas/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Hiperalgesia/etiologia , Mucosa Intestinal , Teste de Cultura Mista de Linfócitos , Camundongos , Modelos Animais , Fenótipo , Reflexo Abdominal , Triquinelose/complicações , Triquinelose/patologia
20.
J Pharmacol Sci ; 116(1): 47-53, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21521930

RESUMO

Mosapride citrate (mosapride), a prokinetic agent with 5-HT(4)-receptor agonistic activity, is known to enhance gastric emptying and alleviate symptoms in patients with functional dyspepsia (FD). As hyperalgesia and delayed gastric emptying play an important role in the pathogenesis of FD, we used in this study balloon gastric distension to enable abdominal muscle contractions and characterized the visceromotor response (VMR) to such distension in conscious rats. We also investigated the effects of mosapride on gastric distension-induced VMR in the same model. Mosapride (3-10 mg/kg, p.o.) dose-dependently inhibited gastric distension-induced VMR in rats. However, itopride even at 100 mg/kg failed to inhibit gastric distension-induced VMR in rats. Additionally, a major metabolite M1 of mosapride, which possesses 5-HT(3)-receptor antagonistic activity, inhibited gastric distension-induced VMR. The inhibitory effect of mosapride on gastric distension-induced visceral pain was partially, but significantly inhibited by SB-207266, a selective 5-HT(4)-receptor antagonist. This study shows that mosapride inhibits gastric distension-induced VMR in conscious rats. The inhibitory effect of mosapride is mediated via activation of 5-HT(4) receptors and blockage of 5-HT(3) receptors by a mosapride metabolite. This finding indicates that mosapride may be useful in alleviating FD-associated gastrointestinal symptoms via increase in pain threshold.


Assuntos
Benzamidas/uso terapêutico , Dilatação Gástrica/fisiopatologia , Fármacos Gastrointestinais/uso terapêutico , Motilidade Gastrointestinal/efeitos dos fármacos , Morfolinas/uso terapêutico , Reflexo Abdominal/efeitos dos fármacos , Agonistas do Receptor 5-HT4 de Serotonina/uso terapêutico , Estômago/inervação , Dor Abdominal/tratamento farmacológico , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/antagonistas & inibidores , Analgésicos não Narcóticos/metabolismo , Analgésicos não Narcóticos/uso terapêutico , Animais , Benzamidas/administração & dosagem , Benzamidas/antagonistas & inibidores , Benzamidas/metabolismo , Benzamidas/farmacologia , Compostos de Benzil/administração & dosagem , Compostos de Benzil/uso terapêutico , Relação Dose-Resposta a Droga , Dispepsia/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/antagonistas & inibidores , Fármacos Gastrointestinais/metabolismo , Granisetron/uso terapêutico , Masculino , Morfolinas/administração & dosagem , Morfolinas/antagonistas & inibidores , Morfolinas/metabolismo , Morfolinas/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Agonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Antagonistas do Receptor 5-HT3 de Serotonina/farmacologia , Agonistas do Receptor 5-HT4 de Serotonina/administração & dosagem , Agonistas do Receptor 5-HT4 de Serotonina/metabolismo , Antagonistas do Receptor 5-HT4 de Serotonina/farmacologia , Estômago/efeitos dos fármacos
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