Transcutaneous electrical nerve stimulation(TENS), acupuncture-needling, and electroacupuncture are useful non-ablative methods in medical practice for relief of pain. These procedures appear to work by causing an increased discharge in afferent nerve fibers which in turn modifies the transmission of impulses in pain pathways. It is known that the mechanism of analagesic effect via these maneuvers are variable depending on the stimulating parameters. For example, the endogenous opioid system is profoundly related to the mechanism when a peripheral nerve stimulation is applied with parameters of low frequency and high intensity. However, when stimulated with parameters of high frequency and high intensity, the reduced activity of dorsal horn neurons is only slightly reversed by a systemic administration of naloxone, a specific opiate antagonist. Thus, the present study was performed to investigate the neurotransmitter that concerns the mechanism of peripheral nerve stimulation with parameters of high frequency and high intensity. We used an iontophoretic application of antagonists of possible related neurotransmitters. The dorsal horn neuron activity which was evoked by squeezing the peripheral cutaneous receptive field, was recorded as an index of pain with a microelectrode at the lumbo-sacral spinal cord. Naloxone, picrotoxin and strychnine were applied at 200nA during a period of conditioning nerve stimulation. We observed the effects of these drugs on the change of dorsal horn neuron activities. The main results of the experiment can be summarized as follows. The spontaneous activity of dorsal horn neurons increased in the presence of glutamate and decreased with GABA. It did not change with naloxone, picrotoxin or strychnine. When naloxone was applied iontophoretically during peripheral nerve stimulation, there was no statistically significant analgesic effect compared with that of the control group. When picrotoxin was applied iontophoretically during peripheral nerve stimulation, the analgesic effect was reduced. When strychnine was applied, the analgesic effect was reduced but did not show a statistically significant difference with the control group. These results suggested that the GABAergic system may have been partially related in the analgesic action of peripheral nerve stimulation with parameters of high frequency and high intensity.
Animal ; Cats ; *Conditioning (Psychology) ; Female ; Iontophoresis ; Male ; Naloxone/*pharmacology ; Neurons/drug effects ; Picrotoxin/*pharmacology ; Spinal Cord/cytology/*drug effects ; Strychnine/*pharmacology ; *Transcutaneous Electric Nerve Stimulation

AIMTo observe the role of melatonin receptor and GABAA receptor in sleeping time prolonged by melatonin in mice.

METHODSThe absence of the righting reflex was considered as the sleep onset and the duration of the loss of the righting reflex was recorded as the sleeping time. The effects of receptor agonist and antagonist on hypnotic activity of melatonin were studied in the paper.

RESULTSPrazosin hydrochloride, the blocker of melatonin 3 receptor, didn't affect the sleeping time prolonged by melatonin in mice. GABA, the endogenous agonist of GABA receptor, significantly potentiated the hypnotic activity of melatonin. When picrotoxin, the ligand of picrotoxin site on GABAA receptor, used together with melatonin, it significantly antagonized the sleeping time prolonged by melatonin, however, bicuculline, the specific antagonist of GABA binding site in GABAA receptor, didn't affect the hypnotic activity of melatonin in mice.

CONCLUSIONMelatonin does not exhibit its potentiation sleeping time in mice through melatonin 3 receptor. Hypnotic activity of melatonin may be mediated through picrotoxin site on GABAA receptor.

Animals ; Bicuculline ; pharmacology ; Male ; Melatonin ; physiology ; Mice ; Mice, Inbred Strains ; Picrotoxin ; pharmacology ; Prazosin ; pharmacology ; Receptors, GABA-A ; physiology ; Receptors, Melatonin ; physiology ; Sleep ; physiology

Previous studies showed that a mixture, Coriaria Lactone (CL), extracted from a traditional Chinese herb Loranthus Parasiticus Mer, had a great excitatory influence on the nervous system, resulting in seizure. But what component in CL causes seizure is unclear. Tutin is a pure chemical component derived from CL. The present experiments were carried out to test if tutin has any epileptogenic action and to preliminarily study the mechanism underlying that action in vitro. The electrical activity of CA1 pyramidal cells, population spikes (PS), evoked by stimulation of the Schaffer collaterals in rat hippocampal slices was recorded extracellularly. The effects of tutin on the PS and the antagonistic actions of CNQX and AP-5 on the tutin-induced effects were investigated. The results are as follows. (1) Superfusion with 40, 30 and 20 microg/ml tutin caused significant increase in the amplitude and number of PS waves evoked by stimulating the Schaffer collaterals. Thirty minutes after superfusion of tutin, the amplitude of the first wave of the PSs was increased by (388.7+/-0.1)%, (317.2+/-19.1)% and (180.9+/-11.6)% in each of the above three groups, respectively, compared with the control (for each group, n=5, P<0.05). (2) With increase in amplitude, the PS number was increased to 4~11 waves from a single wave in the control and manifested multiple epileptiform discharges 30 min superfusion with tutin. (3) Spontaneous epileptiform discharges of CA1 pyramidal cells were obtained in 9 out of 34 cases after tutin superfusion. (4) The tutin-induced multiple epileptiform discharges of the CA1 pyramidal cells were completely blocked by CNQX, in aspects of both amplitude and number of the PS. Following the application of AP-5, the increase in the wave number of the tutin-induced epileptiform discharges was inhibited but the increase in the amplitude of the discharges was not significantly affected. These results indicate that tutin can induce typical multiple epileptiform discharges of CA1 pyramidal cells in rat hippocampal slices and might be used as an efficient epileptogenic agent, and that the excitable glutamate receptors, especially the non-NMDA receptors, may participate in the genesis of tutin-induced epileptiform discharges.
Animals ; Electrophysiology ; Epilepsy ; chemically induced ; physiopathology ; Female ; Hippocampus ; physiopathology ; Male ; Picrotoxin ; analogs & derivatives ; Pyramidal Cells ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Sesquiterpenes ; pharmacology

.This study is to investigate the analgesic effect produced by intrathecal injection (ith) of oxysophoridine (OSR) and the mechanism of GABAA receptor. Warm water tail-flick test was used to detect the analgesic effect of OSR (12.5, 6.25, and 3.13 mg.kg-1 ith) and to observe the influence of GABA (gamma aminobutyric acid) agonist or antagonist on the analgesic effect of OSR in mice. Immunohistochemistry method were used to detect the influence of OSR (12.5 mg.kg-1, ith) on the GABAARalpha1 protein expression in spinal cord. The results obtained covers that OSR (12.5 and 6.25 mg.kg-, ith) alleviates pain significantly with the warm water tail-flick test (P<0.05, P<0.01), the rate of pain threshold increases by 68.45%; GABA and muscimol (MUS) produces analgesic synergism together with the OSR, picrotoxin (PTX) and bicuculline (BIC) antagonize the analgesic effect of OSR; OSR (12.5 mg.kg-1, ith) significantly increase the positive number of GABAARalpha1 nerve cell in spinal cord (P<0.01) and significantly decrease the average grey levels (P<0.01). In conclusion, OSR intrathecal injection has significant analgesic effect. And GABAA receptor in spinal cord is involved in the analgesic mechanism.
Alkaloids ; administration & dosage ; pharmacology ; Analgesics ; administration & dosage ; pharmacology ; Animals ; Bicuculline ; pharmacology ; Female ; GABA-A Receptor Agonists ; pharmacology ; GABA-A Receptor Antagonists ; pharmacology ; Injections, Spinal ; Male ; Mice ; Muscimol ; pharmacology ; Pain Threshold ; drug effects ; Picrotoxin ; pharmacology ; Random Allocation ; Receptors, GABA-A ; metabolism ; Spinal Cord ; metabolism ; gamma-Aminobutyric Acid ; pharmacology