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Objective: Low-frequency stimulation (LFS) exerts suppressive effects in kindled animals. It is believed that overstimulated glutamatergic and decreased GABAergic transmission have long been associated with seizure activity. In this study, we investigated the effect of electrical LFS on different parameters of spontaneous excitatory and inhibitory post-synaptic currents (sEPSCs and sIPSCs) in hippocampal CA1 pyramidal cells in kindled animals. Materials and Methods: In this experimental study, rats were kindled by electrical stimulation of the hippocampal CA1 area in a semi-rapid manner (12 stimulations/day). The animals were considered fully kindled when they showed stage 5 seizures on three consecutive days. One group of animals received LFS 4 times at 30 seconds, 6 hours, 18 and 24 hours following the last kindling stimulation. Each LFS consisted of 4 packages at 5 minutes intervals. Each package of LFS consisted of 200 pulses at 1 Hz and each monophasic square wave pulse duration was 0.1 millisecond. At 2-3 hours post-LFS, acute hippocampal slices were prepared and a whole cell patch clamp recording was performed in all animals to measure the different parameters of sEPSCs and sIPSCs. Results: In kindled animals, the inter-event interval (as an index of occurrence) of sEPSCs decreased, whereas sIPSC increased. In addition, the decay time constant of sIPSCs as an index of the duration of its activity decreased compared to the control group. There was no significant difference in other parameters between the kindled and control groups. Application of LFS in kindled animals prevented the observed changes. There was no significant difference between the measured parameters in kindled+LFS and control groups. Conclusion: LFS application may prevent seizure-induced increase in the occurrence of sEPSCs and seizure-induced decrease in occurrence and activity duration of sIPSCs.

Background and the purpose of the study The hippocampal formation is involved in nociception. Prenatal serotonin depletion results in a significant decrease in the concentration of nociceptive sensitivity during the second phase of behavioral response in the formalin test. Methods A microdialysis probe was inserted via a guide cannula into the right CA1 region of the hippocampus. Extracellular serotonin (5HT) and its 5- hydroxyindoleacetic acid (5HIAA) metabolite overflow were collected every 10 min during the formalin test and measured by HPLC with electrochemichal detector. Results Compared to the sham group, formalin injection in the hind paw of the rat significantly increased 5HT after 10, 30, 40, and 50 min and increased 5HIAA after 10, 30, 40, 50, and 60 min collection time periods in hippocampal dialysate. (n=6 for each group at each sampling time). In the formalin treated rats serotonin and 5HIAA concentrations increased in the biphasic pattern in concert with the first and second phases of formalin pain. Conclusion The hippocampal formation might be involved in the processing of nociceptive information and serotonin-related mechanisms in the hippocampus may play a role in the biphasic behavioral responses to formalin noxious stimulation.

Objective It is well known that intracerebroventricular (ICV) and supraspinal injections of orexin-A elicit analgesia, but the mechanism(s) of action remains unidentified. This study aims to characterize the effect of orexin-A on rostral ventromedial medulla (RVM) neurons which are involved in the descending nociception modulating pathway. Materials and Methods In this experimental study, we injected orexin-A or vehicle di- rectly into rats’ ICV while the tail flick (TF) latencies were measured and the on- and off-cell firing activities were monitored for more than 60 minutes. Results In response to noxious stimuli on the tail, we observed increased firing rate of on-cells and a decreased association with the firing rate of off-cells and in neutral cells the firing rate was unchanged just prior to tail flicking. ICV injection of orexin-A decreased the spontaneous firing rate of on-cells (the type of RVM neurons believed to have facilitatory action on nociception). Furthermore, orexin-A increased firing rate of off-cells (the type of RVM neurons believed to have an inhibitory action on nocicep- tion). Orexin-A reduced the TF-related responses of on-cells and TF-related pause duration of off-cells. Conclusion These results have shown that the analgesic effect produced by orexin-A may be induced by brainstem neurons. It is suggested that the orexinergic system from the hypothalamus to the RVM may have a potential role in modulation of nociceptive transmission.

The rostral ventromedial medulla (RVM) acts a key role in the descending inhibitory pain modulation. Neuropeptide orexin-A (ORXA) is confined to thousands of neurons in the lateral hypothalamus (LH). While RVM gets the orexinergic projections, the orexin receptors are also expressed in this structure. The aim of this study was to specify the cellular effects of ORXA on RVM neurons in vitro by using the whole cell patch-clamp recording. RVM neurons were classified into three types based on their electrophysiological characteristics. Type 1 neurons exhibited an irregular spontaneous activity which was interrupted by periods of pause in 25% of recorded neurons. Type 2 neurons did not show any spontaneous baseline activity (53.8% of recorded neurons). Type 3 neurons fired repetitively without interruption (51.2% of recorded neurons). ORXA had either inhibitory or excitatory effects on 53.8% (7/13) of type 1 neurons. ORXA excited 46.4% (13/28) of type 2 neurons and 27.3% (3/11) of type 3 neurons. The excitatory effect of ORXA observed in type 2 neurons was suppressed by an orexin 1 receptor (OXR1) antagonist, SB-334867. Briefly, we hypothesized that the ORXA mediated excitation and/or inhibition in RVM neurons might work as a mechanism to modulate pain processing by orexinergic neurons.

Introduction: Adenosine has been considered as a fine-tuner of the neurotransmitters in the nervesystem. Adaptive changes in the brain adenosine system occur in some patho-physiological situations suchas chronic exposure to morphine. In this study, the adaptive changes in the adenosine deaminase activity asa key enzyme in the adenosine metabolism that converts adenosine to inosine and ammonia, irreversibly,due to morphine dependence and tolerance to anti-nociceptive effects of sodium-salicylate wereinvestigated.Materials and Methods: Morphine dependence was induced by morphine administration in tap water(0.4mg/ml for 24 days). Tolerance to sodium-salicylate was induced by 6 i.p. injection (1 injection/day) ofsodium-salicylate. Tolerance to antinociceptive effects of sodium-salicylate was measured by tail flick (TF)and hot plate (HP) tests. Right hippocampus was dissected, homogenized at phosphate buffer, centrifugedand then the supernatant fraction was isolated. Protein content of the samples was measured by theBradford method. Hippocampus adenosine deaminase activity was measured by a calorimetric method ofenzyme assay which is based on the direct measurement of the produced ammonia from excessiveadenosine degradation by adenosine deaminase.Results: Daily injection of Sodium-salicylate produced antinociception in early days by latency increaserather than saline injection (P0.05). Injection of morphine(5mg/Kg) at the day 7 showed more increase in the latency of saline injected rather than sadium-salicylateinjected (P0.05).Conclusion: This decline in the adenosine deaminase activity may be related with adaptation in brainadenosine system subsequent of dependent to morphine or tolerance to sodium-salicylate.