RESUMO
Pain and learning memory have striking similarities in synaptic plasticity. Activation of the N-methyl-D-aspartic acid receptors 2B subunits (NR2B-NMDAs) is responsible for the hippocampal LTP in memory formation. In our previous studies, we found the significant enhancement of CA1 hippocampal long-term potentiation (LTP) induced by high-frequency stimulation (HFS) in rats with chronic visceral pain. However, it is unclear whether the NR2B-NMDAs are required for the LTP in chronic visceral pain. In this study, a rat model with irritable bowel syndrome (IBS) was established by colorectal distention (CRD). The sensitivity of visceral pain and HFS-induced LTP at SC-CA1 synapses were significantly enhanced in IBS-like rats (p<0.05). In addition, hippocampal NR2B protein levels significantly increased in IBS-like rats (p<0.05). To test whether NR2B-NMDAs are responsible for the LTP, effects of Ro 25-6981, a selective antagonist of NR2B-NMDAs, on field potential in CA1 region were investigated in vitro. Our results demonstrated that Ro 25-6981 dose-dependently inhibited the facilitation of CA1 LTP in IBS-like rats. The plausible activation mechanism of hippocampal NR2B-NMDAs in the LTP enhancement was further explored. Western blot data indicated that expression of tyrosine phosphorylated NR2B protein in hippocampus significantly enhanced in IBS-like rats. Accordingly, genistein, a specific inhibitor of tyrosine kinases, dose-dependently blocked the facilitation of hippocampal LTP in IBS-like rats. Furthermore, EMG data revealed that intra-hippocampal injection of Ro 25-6981 dose-dependently attenuated the visceral hypersensitivity. In conclusion, hippocampal NR2B-NMDAs are responsible for the facilitation of CA1 LTP via tyrosine phosphorylation, which leads to visceral hypersensitivity.
Assuntos
Dor Crônica/fisiopatologia , Hipocampo/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Potenciação de Longa Duração/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Dor Visceral/fisiopatologia , Animais , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/fisiopatologia , Dor Crônica/tratamento farmacológico , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/farmacologia , Genisteína/farmacologia , Hipocampo/efeitos dos fármacos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/fisiopatologia , Síndrome do Intestino Irritável/tratamento farmacológico , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Fenóis/farmacologia , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , Ratos Sprague-Dawley , Sinapses/efeitos dos fármacos , Sinapses/fisiologia , Dor Visceral/tratamento farmacológicoRESUMO
To investigate the electrophysiologic characteristics of f-wave amplitude and to evaluate its role in development and persistence of chronic atrial fibrillation (AF) associated with rheumatic heart disease (RHD). Methods: Epicardial mapping was performed in 44 patients with chronic AF of RHD who underwent heart valve surgery. Ten patients with supraventricular tachycardia served as the control group. Results:The f-wave amplitude of left atrium (LA) and middle and low LA posterior regions were significantly lower than those of the control group. The f-wave amplitudes of the upper, middle and low sections in LA posterior region were significantly lower than those in right atrium (RA) (P<0.05). The f-wave amplitudes were compared before and after electrocardioversion in 14 patients with chronic AF. The mean atrial electrogram amplitude during sinus rhythm was significantly higher than that during AF (P<0.01).The f-wave amplitude in left appendage was higher than that in LA posterior region (the upper,middle and the lower part),P<0.05.The f-wave amplitude in the upper section of LA was significantly higher than that in the middle section. The f-wave amplitude in AF group was not correlated to the diameter or volume of both atria. Conclusion: There are amplitudes differences between the upper, middle and lower LA,suggesting that the middle and lower sections of LA posterior wall may be the region producing anisotropy and reentrant circle.
RESUMO
To investigate the electrophysiologic characteristics of f-wave amplitude and to evaluate its role in development and persistence of chronic atrial fibrillation (AF) associated with rheumatic heart disease (RHD). Methods: Epicardial mapping was performed in 44 patients with chronic AF of RHD who underwent heart valve surgery. Ten patients with supraventricular tachycardia served as the control group. Results:The f-wave amplitude of left atrium (LA) and middle and low LA posterior regions were significantly lower than those of the control group. The f-wave amplitudes of the upper, middle and low sections in LA posterior region were significantly lower than those in right atrium (RA) (P<0.05). The f-wave amplitudes were compared before and after electrocardioversion in 14 patients with chronic AF. The mean atrial electrogram amplitude during sinus rhythm was significantly higher than that during AF (P<0.01).The f-wave amplitude in left appendage was higher than that in LA posterior region (the upper,middle and the lower part),P<0.05.The f-wave amplitude in the upper section of LA was significantly higher than that in the middle section. The f-wave amplitude in AF group was not correlated to the diameter or volume of both atria. Conclusion: There are amplitudes differences between the upper, middle and lower LA,suggesting that the middle and lower sections of LA posterior wall may be the region producing anisotropy and reentrant circle.
