RESUMO
Lidocaine injections in the rostral ventromedial medulla (RVM) have been shown to produce significant reduction of neuropathic manifestations in rats. This effect has been attributed to selective block of a pain descending facilitatory system, responsible for chronic pain. However, recent observations from our laboratory did not provide confirmation to this hypothesis. We aimed, therefore, to investigate the spinal synaptic mechanisms activated by lidocaine injections in the RVM. Rats were subjected, under deep anesthesia, to the induction of mononeuropathy on one hindpaw, and to the stereotaxic implantation of chronic cannulae in the RVM for the injection of lidocaine or GABA antagonists. Implanted intrathecal catheter in the lumbosacral space was used for the injection of specific antagonists to GABA, 5HT, glycine, noreadrenaline and dopamine, prior to lidocaine. Tactile and cold hyperreactivity and heat hyperalgesia were assessed using von Frey hair filaments, acetone drop test and heat-induced paw withdrawal, respectively. Lidocaine injections produced significant inhibition of all neuropathic manifestations. Intrathecal injection of antagonists to GABA (bicucullin, picrotoxin and saclofen), serotonin 5HT(1-2) (ketanserin and methysergide) and α- (phentoalmine, yohimbine) and ß- (propranolol) adrenergic receptors, suppressed the lidocaine inhibitory effects; while partial or no attenuation were observed following pretreatment with glycine and dopamine D(2/3) antagonists. Comparable effects were observed with RVM injection of GABA antagonists. Lidocaine injection in the RVM results in a release of the descending pain-inhibitory systems from a tonic gabaergic inhibition. This descending system involves the activation of gabaergic, serotonergic and adrenergic mechanisms at the level of the spinal dorsal horn.
Assuntos
Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/fisiologia , Lidocaína/administração & dosagem , Mononeuropatias/tratamento farmacológico , Mononeuropatias/etiologia , Medição da Dor , Animais , Temperatura Baixa , Modelos Animais de Doenças , Feminino , Temperatura Alta , Injeções Espinhais , Microinjeções , Medição da Dor/métodos , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: The neurodevelopment of hippocampus and prefrontal cortex are known to influence different functions in normal and pathological conditions including cognition and sensorimotor functions. The neonatal lesion of the ventral hippocampus (VH) in rats has been established as an animal model of schizophrenia and is used to study postpubertal changes in behavior and neurobiology. In order to investigate whether early VH lesion in rats alters the expression of genes implicated in schizophrenia pre- and post-puberty, we studied the mRNA expression of neuropeptides (substance P, dynorphin and enkephalin), dopamine D1, dopamine D2, and NMDA (subunits NR1 and NR2A) receptors in this animal model. METHODS: Rat pups were lesioned at postnatal day 7 by injecting ibotenic acid into the VH bilaterally, and then sacrificed at age 35 (pre-puberty) and 65 (post-puberty) days. Another group of adult rats had the same lesion in the VH, to independently assess the effects of the lesion on the expression of genes, and then sacrificed at week 4 and 8 post lesion. Sham groups were injected with cerebrospinal fluid using the same procedure. Brains were removed and sectioned to study the mRNA expression using in situ hybridization (ISH). RESULTS: The main results are the postpubertal onset of increased NR1 mRNA expression in all cortical regions and decreased dopamine D2 receptor, substance P and enkephalin mRNA expression in the striatum only in rats lesioned as neonates. These changes were not observed in the adult group with VH lesion. CONCLUSIONS: Our results demonstrate that the postpubertal behavioral changes in this animal model (and possibly schizophrenia) are related to postpubertal onset of changes in the development of functions and interactions of the dopamine and glutamate receptors in the mesocortical system.
Assuntos
Lesões Encefálicas/patologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Hipocampo/metabolismo , Neuropeptídeos/genética , RNA Mensageiro/metabolismo , Receptores Dopaminérgicos/genética , Receptores de Glutamato/genética , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Lesões Encefálicas/induzido quimicamente , Dinorfinas/genética , Dinorfinas/metabolismo , Encefalinas/genética , Encefalinas/metabolismo , Feminino , Hipocampo/crescimento & desenvolvimento , Ácido Ibotênico , Masculino , Neuropeptídeos/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Receptores Dopaminérgicos/metabolismo , Receptores de Glutamato/classificação , Receptores de Glutamato/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Substância P/genética , Substância P/metabolismoRESUMO
OBJECTIVE: Massive gastric dilatation is a very serious condition that is extremely rare in patients with no history of gastrointestinal disease. Several cases have been reported in patients with eating disorders, particularly after a binge. We report here the case of a young woman who developed severe gastric dilatation after a single binge. METHODS: A computed tomographic (CT) scan of the abdomen was done and a psychiatric evaluation was performed. RESULTS: The diagnosis of acute gastric dilatation was confirmed and superior mesenteric artery syndrome was excluded. The patient responded to nasogastric drainage and bowel rest. She was also found to have situational anxiety and depressive symptoms as well as a nonspecified eating disorder. CONCLUSION: This case illustrates the serious sequel of even a single binge in any patient with abnormal dietary habits, and demonstrates the useful role of the CT scan in the diagnosis.
Assuntos
Anorexia Nervosa/diagnóstico por imagem , Bulimia/complicações , Dilatação Gástrica/diagnóstico por imagem , Adulto , Anorexia Nervosa/psicologia , Bulimia/diagnóstico por imagem , Bulimia/psicologia , Comorbidade , Diagnóstico Diferencial , Feminino , Dilatação Gástrica/psicologia , Humanos , Estresse Psicológico/complicações , Tomografia Computadorizada por Raios X , Redução de PesoRESUMO
The proper maturation of the hippocampus is essential for the development of different behaviours, including memory, pain responses and avoidance. The mechanisms involved in the neurodevelopment of nociception have also been implicated in several neuropsychiatric disorders. The neonatal lesion of the ventral hippocampus (VH) in rats, an animal model of schizophrenia, can be utilized to study the developmental neurobiology of animal behaviour. We examined the nociceptive responses in this animal model at different stages of development. Rat pups were lesioned at postnatal day 7 by injecting ibotenic acid into the VH bilaterally, and then tested for thermal and mechanical nociception at the age of 35, 65 and 180 days. The nociceptive tests used were the hot plate (HP), paw pressure (PP) and tail flick (TF) tests. Another group of adult rats had the same lesion in the VH and then underwent the same tests at 28, 56 and 168 days post-lesions. When compared with sham controls, the rats with neonatal VH lesion showed decreased latency for the HP and PP tests only after puberty. The TF test showed significant increase in latency for both groups at age 65 and 180 days. The adult rats with VH lesion showed no major changes over all periods of testing. These results suggest that early lesion of VH can alter the development of the neural mechanisms involved in the processing of thermal and mechanical nociception.
Assuntos
Hipocampo/fisiologia , Hiperalgesia/fisiopatologia , Dor/fisiopatologia , Fatores Etários , Animais , Animais Recém-Nascidos , Comportamento Animal , Encefalopatias/fisiopatologia , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Temperatura Alta/efeitos adversos , Ácido Ibotênico/toxicidade , Masculino , Dor/induzido quimicamente , Medição da Dor/métodos , Gravidez , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Tato/fisiologiaRESUMO
Recent imaging reports demonstrate the activation of the orbitofrontal cortical (OFC) area during acute and chronic pain. The aim of this study was to compare the effects of chronic perfusion of this area with morphine on nociception in control rats and in rats subjected to mononeuropathy. Chronic perfusion of morphine, using miniosmotic pumps, produced significant and naloxone-reversible depression of tactile and cold allodynias and thermal hyperalgesia, observed in neuropathic rats, while it produced significant elevation and naloxone insensitive increase of acute nociceptive thresholds in control rats. The observed results support the idea that this area is a component of a flexible cerebral network involved in pain processing and perception.
Assuntos
Analgésicos Opioides/uso terapêutico , Lobo Frontal/efeitos dos fármacos , Mononeuropatias/tratamento farmacológico , Morfina/uso terapêutico , Dor/tratamento farmacológico , Animais , Comportamento Animal , Modelos Animais de Doenças , Vias de Administração de Medicamentos , Esquema de Medicação , Lobo Frontal/fisiopatologia , Hiperalgesia/etiologia , Mononeuropatias/complicações , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Dor/etiologia , Medição da Dor/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Fatores de TempoRESUMO
The mesocorticolimbic circuitry has been implicated in the pathophysiology of several neuropsychiatric syndromes like chronic pain and addiction. The aim of this study was to evaluate the effects of dizocilpine (MK-801), a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, on sensorimotor behaviors and the consequent changes in the dopamine, glutamate, and opiate systems in rats. Five groups of rats were subjected to acute tests for nociception (hot plate and paw pressure) before and after MK-801 (0.05, 0.1, 0.2 and 0.4 mg/kg, i.p.) or saline. Another two groups received daily i.p. saline or MK-801 (0.4 mg/kg) for 15 days. The nociceptive tests were performed on days 1, 7, and 14. On day 15 the rats received the last injection and were immediately sacrificed. We measured the mRNA expression, by in situ hybridization (ISH), of various dopamine and glutamate receptors, and enkephalin (Enk), dynorphin (Dyn), and substance P (SP) in the striatum, nucleus accumbens (NAC), piriform and cingulate cortex. Acute MK-801, dose-dependently, resulted in hyperalgesia. The chronic effects of 0.4 mg/kg MK-801 showed an extinction of the acute hyperalgesic effects especially with the hot plate test. The ISH studies revealed a decrease in mRNA expression of Enk and SP in the striatum and NAC. Our results indicate that the reversal of acute MK-801-induced hyperalgesia, with repeated exposure to systemic MK-801, is not directly related to changes in dopamine and glutamate receptors and might involve alteration of the striatal neuropeptide system.