Effects And Mechanism Of Apelin On Central Pain Modulation In Rats

Objective:The effects and mechanism of apelin in central pain modulation of rats were investigated by using a pain model of radiant heat stimulation tail-flick test.Methods:(1) The latency of tail-flick induced by radiant heat stimulation was used as measurements of pain threshold(PT) in male SD rats.Microdoses of normal sodium(NS), morphine or apelin were injected into lateral cerebral ventricles. The changes of pain threshold were observed within 60 min after administration.(2) The male SD rats were divided into two groups, NS and apelin groups. The changes of nNOS in caudate nucleus, hippocampus and cortical layer were observed by immunofluorescence(IF) and laser confocal microscopy at 30min after administration.(3) Brain and blood samples were taken from the decapitated rats at 30min after micro-injection of NS or apelin into lateral cerebral ventricles. The changes of NO and NOS in serum, caudate nucleus, hippocampus and cortical layer were examined by nitrate reductase(NR).(4) Brain and blood samples were taken from the decapitated rats at 30min after micro-injection of NS or apelin into lateral cerebral ventricles. The levels of cAMP and cGMP in blood, caudate nucleus and hippocampus were measured byradioimmunoassay(RIA).Results:(1) Compared with the NS group, pain threshold was significantly reduced within 10-30 minutes after apelin administration and thereafter slowly restored, but remained significant 60 minutes later compared with NS group (P<0.01) .(2) nNOS's double fluorescein stain could be found in every encephalic region by laser confocal microscopy.nNOS labeled by fluorescein isothiocyanate(FITC) presented as green fluorescence granules which were distributed in cytoplasm. The red fluorescenc granules were cellular nucleus labeled by propidium iodide(PI). The cell appearance was intact, the fluorescence color of cellular nucleus and cytoplasm was distinct. The expression of nNOS was significantly descreased in the caudate nucleus and hippocampus after micro-injection of apelin (P<0.05 or P<0.01) .(3) The content of NO or NOS was significantly decreased in serum, caudate nucleus and hippocampus after micro-injection of apelin (P<0.05 or P<0.01) .(4) The cAMP levels in blood, caudate nucleus and hippocampus were increased significantly, while the cGMP levels were dereased after injecting apelin (P<0.05 orP<0.01) .Conclusion:(1) Micro-injection of apelin has a hyperalgesica effect.(2) The hyperalgesica effect may be associated with caudate nucleus and hippocampus.(3) Apelin may generate hyperalgesica effect by reducing the contents of NOS in caudate nucleus and hippocampus, NO in serum, caudate nucleus and hippocampus, and cGMP in caudate nucleus, hippocampus and blood plasma. The mechanism may be partially associated with an apelin-NO-cGMP metabolic pathway.Apelin may generate the hyperalyesia effect by elevating the content of cAMP in the caudate nucleus, hippocampus and blood plasma. The mechanism may be associated with an apelin-cAMP metabolicpathway.