ABSTRACT
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.
Subject(s)
Chronic Pain/physiopathology , Hippocampus/physiopathology , Irritable Bowel Syndrome/physiopathology , Long-Term Potentiation/physiology , Receptors, N-Methyl-D-Aspartate/metabolism , Visceral Pain/physiopathology , Animals , CA1 Region, Hippocampal/drug effects , CA1 Region, Hippocampal/physiopathology , Chronic Pain/drug therapy , Disease Models, Animal , Excitatory Amino Acid Antagonists/pharmacology , Genistein/pharmacology , Hippocampus/drug effects , Hyperalgesia/drug therapy , Hyperalgesia/physiopathology , Irritable Bowel Syndrome/drug therapy , Long-Term Potentiation/drug effects , Male , Phenols/pharmacology , Piperidines/pharmacology , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/metabolism , Rats, Sprague-Dawley , Synapses/drug effects , Synapses/physiology , Visceral Pain/drug therapyABSTRACT
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.
ABSTRACT
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.
