Enzyme-linked immunosorbent assay(ELISA) and metabolomics were used to analyze and compare two animal models of heart-kidney insomnia, in order to explore a more ideal animal model and preliminarily explore the essence of heart-kidney insomnia. Based on the clinical symptoms and disease characteristics of heart-kidney insomnia, the animal model of heart-kidney insomnia was reproduced through intraperitoneal injection with p-chlorophenylalanine(PCPA) and multi-factor interaction. The animal model of disease-syndrome combination was evaluated by behavioral observation, ELISA and metabolomics. Wistar rats were randomly divided into normal group, PCPA group and compound model group(FH). The rats' behavior, body weight, adrenal index and spleen index were recorded. The levels of corticotropin releasing hormone(CRH) and adrenocorticotropin(ACTH) in serum were detected by ELISA, and the differential metabolites in serum were detected by UPLC-QE-MS. The body weight and adrenal index in FH group were significantly lower than those in PCPA group(P<0.05); whereas ACTH and CRH in FH group were significantly higher than those in PCPA group by ELISA; nine potential biomarkers were identified by serum sample statistics. There were four main metabolic pathways in cardiorenal insomnia: pentose phosphate metabolism, alanine, aspartic acid and glutamic acid metabolism, histidine metabolism, and taurine and subtaurine metabolism. PCPA and multi-factor interaction method can successfully replicate the insomnia model, but multi-factor modeling method is more similar to clinical traditional Chinese medicine syndrome. Animal behavior, ELISA and metabolomics were used to evaluate the rat model of cardiorenal insomnia from in vitro to in vivo, from macro to micro, and from individual to the whole.
Animals ; Disease Models, Animal ; Medicine, Chinese Traditional ; Metabolome ; Rats ; Rats, Wistar ; Serum/metabolism* ; Sleep Initiation and Maintenance Disorders/metabolism*

Involvement of the peripheral nerveous system by diabetes is referred to as diabetic neuropathy. The frequency of diabetic neuropathy ranges from 5% to 60% and the pain management is one of the greatest problem. The patient was a 57-year-old man who has been treated with diabetes(DM type IIa) for about 12 years. The symmetrical pain, swelling and sensory loss on feet were started 3 months before admission and the burning pain was intensified at night with resultant insomnia. The systoms were aggravated 1 month ago and they were not relieved by any medication and physical therapy. We attempted lumbar epidural block to the patient and the result was good. So we performed a permanent lumbar sympathetic ganglion block with neurolytics(99.9% alcohol) for the long term relief of pain. The patient was satisfied with the result of the block and discharged.
Burns ; Diabetic Neuropathies* ; Foot ; Ganglia, Sympathetic ; Humans ; Metabolism ; Middle Aged ; Pain Management* ; Sleep Initiation and Maintenance Disorders ; Sympathetic Nervous System

In this paper the response characteristic of the nerve fiber to the modulation magnetic field induction is studied by using the method of numeric simulation. It is found that the nerve fiber is sensitive to the low frequency modulated signal but not to the high frequency carrier wave. A simulative EEG signal generator is developed according to the change of EEG rhythm during the sleep. The simulative EEG square wave is modulated by high-frequency magnetic impulse. The modulation magnetic field is coupled into the rabbit's brain to study the influence of magnetic stimulation on the discharge of 5-hydroxytryptamine (5-HT) nerve cell. The experiment results demonstrate that discharge frequency of median raphe nuclei related to sleep changes significantly and the discharge becomes slow, which shows that magnetic stimulation can inhibit electrical activity of 5-HT nerve cell and provide a new way to improve insomnia.
Animals ; Brain ; metabolism ; physiology ; Computer Simulation ; Electroencephalography ; Electromagnetic Fields ; Electrophysiology ; Humans ; Neurons ; physiology ; Rabbits ; Raphe Nuclei ; metabolism ; physiology ; Serotonin ; metabolism ; Sleep ; physiology ; Sleep Initiation and Maintenance Disorders ; metabolism ; physiopathology

With the ultra high performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-MS)-based metabonomics technology, this study aims to analyze the effect of Chaiqin Ningshen Granules(CNG) on endogenous metabolites in insomnia rats of liver depression syndrome and explore the sleep-improving mechanism of this prescription. Parachlorophenylalanine(PCPA, ip) and chronic stimulation were combined to induce insomnia of liver depression pattern in rats, and the effect of CNG on the macroscopic signs, hemorheology, and neurotransmitters in the hippocampus of insomnia rats of liver depression syndrome was observed. After the administration, rat hippocampus was collected for liquid chromatography-mass spectrometry(LC-MS) analysis of the metabolomics. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed for analyzing the metabolites in rat hippocampus and screening potential biomarkers. MetPA was used to yield the related metabolic pathways and metabolic networks. The results show that the drugs can significantly improve the mental state, liver depression, and blood stasis of rats, significantly increase the content of 5-hydroxytryptamine(5-HT) and gamma aminobutyric acid(GABA) in hippocampus(except low-dose CNG), and significantly reduce the content of glucose(Glu)(except low-dose CNG). Among them, estazolam and high-dose CNG had better effect than others. Metabolomics analysis yielded 27 potential biomarkers related to insomnia. MetPA analysis showed 4 metabolic pathways of estazolam in intervening insomnia and 3 metabolic pathways of high-dose CNG in intervening insomnia, involving purine metabolism, glycerophospholipid metabolism, histidine metabolism, and caffeine metabolism. CNG can alleviate insomnia by regulating endogenous differential metabolites and further related metabolic pathways. The result lays a basis for further elucidating the mechanism of CNG in improving sleep.
Animals ; Biomarkers ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/pharmacology* ; Estazolam ; Hippocampus/metabolism* ; Metabolomics/methods* ; Rats ; Sleep ; Sleep Initiation and Maintenance Disorders/drug therapy*

Restless legs syndrome (RLS) is a neurological disorder characterized by an irresistible urge to move one's body to stop uncomfortable or odd sensations. It most commonly affects the legs. Moving the affected body part, such as walking or stretching provide relief the urge to move the legs and any accompanying unpleasant sensation partially or totally. RLS is relatively common, affecting 5 to 15 % of the general population, with prevalence rates increasing alongside age. Restless legs syndrome can lead to sleep-onset or sleep-maintenance insomnia, and occasionally excessive daytime sleepiness, all leading to significant morbidity. Dopaminergic systems are known to be strongly related with RLS that are closely linked to CNS iron homeostasis. Besides defective dopaminergic system that is closely related with iron metabolism, genetic factors play a role in early-onset individual with a positive family history. The diagnosis can be made based on the symptom characteristics, differential diagnosis is important because many conditions could mimic RLS symptoms. Dopamine agonists (DAs) have been considered the first-line therapy, but with the growing appreciation of problems associated with long-term treatment, particularly augmentation and impulse control disorder, alpha-2-delta drugs, such as gabapentin, are now considered the first line of treatment in patients with troublesome RLS. In more severe cases, a combination therapy may be required.
Diagnosis* ; Diagnosis, Differential ; Dopamine Agonists ; Homeostasis ; Humans ; Iron ; Leg ; Metabolism ; Nervous System Diseases ; Prevalence ; Restless Legs Syndrome* ; Sensation ; Sleep Initiation and Maintenance Disorders ; Walking

OBJECTIVETo compare the difference in the efficacy between acupuncture and oral administration of trazodone and the expressions of neurotransmitters in patients of insomnia differentiated as liver stagnation transforming into fire.

METHODSSeventy patients of insomnia differentiated as liver stagnation transforming into fire were randomized into an observation group and a control group, 35 cases in each one. In the observation group, acupuncture therapy was adopted at Shenmen (HT 7), Baihui (GV 20), Yintang (GV 29), Hegu (LI 4), Taichong (LR 3), etc. The needles were retained for 20 min each time. The treatment was given once a day, the treatment of 2 weeks made one session. In the control group, trazodone, 100 mg, oral administration, once a day, the treatment of 2 weeks made one session. Two sessions were required in the two groups. The scores in Pittsburgh sleep quality index (PSQI) and Asberg rating scale for side effects (SERS), the levels of neurotransmitters such as 5-hydroxy tryptamine (5-HT) and norepinephrine (NE) and the expressions of protein kinase C (PKC) and brain-derived neurotrophic factor (BDNF) in peripheral blood were observed before and after treatment in the two groups.

RESULTSPSQI score and SERS score after treatment were all decreased compared with those in both groups before treatment (both P<0. 05). After treatment, PSQI score and SERS score in the observation group were lower apparently than those in the control group (both P<0. 05). After treatment NE content and PKC level were decreased; 5-HT content and BDNF mRNA were increased compared with those in both groups before treatment (all P<0. 05). NE content and PKC level in the observation group were lower apparently than those in the control group (both P<0. 05). The serum 5-HT content and BDNF mRNA expression in the observation group were higher than those in the control group separately (both P<0. 05).

CONCLUSIONAcupuncture therapy improves the sleeping quality of patients of insomnia differentiated as liver stagnation transforming into fire, and reduces serum NE level and increases 5-HT content and BDNF expression, which achieves the better efficacy as compared with the oral administration of trazodone. It is one of the effective approaches to the treatment of insomnia differentiated as liver stagnation transforming into fire.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Brain-Derived Neurotrophic Factor ; genetics ; metabolism ; Female ; Humans ; Liver ; physiopathology ; Male ; Neurotransmitter Agents ; genetics ; metabolism ; Norepinephrine ; genetics ; metabolism ; Serotonin ; metabolism ; Sleep Initiation and Maintenance Disorders ; genetics ; metabolism ; physiopathology ; therapy ; Treatment Outcome

OBJECTIVETo evaluate the effect mechanism of warm acupuncture combined with auricular point sticking therapy and its efficacy on insomnia by monitoring the level of brain neurotransmitters in the insomnia patients.

METHODSOne hundred and thirty patients with insomnia were randomized into an observation group and a control group, 65 cases in each one. In the observation group, based on the treating principle of warming yang and benefiting qi, acupuncture was applied to Xinshu (BL 15), Pishu (BL 20), Shenshu (BL 23), Yaoyangguan (GV 3), Baihui (GV 20), Neiguan (PC 6) and Shenmen (HT 7). Warm acupuncture was supplemented at Xinshu (BL 15), Pishu (BL 20), Shenshu (BL 23) and Yaoyangguan (GV 3). The treatment was given once every day. In the control group, estazolam tablets, 0. 5 to 1 mg were prescribed for oral administration, 30 min before sleep at night. The treatment of 14 days was taken as one session and 2 sessions were required in the two groups. The encephal of luctuograph technology was used to observe the sleep quality and brain neurotransmitters before and after treatment in the two groups and the efficacy was compared between the two groups.

RESULTSThe total effective rate was 83.1% (54/65) in the observation group and 87.7% (57/65) in the control group. The efficacy was similar between the two groups (P > 0.05). In the observation group, after treatment, 5-HT and GABA/Glu were all increased compared with those before treatment (P < 0.05, P < 0.01) and norepinephrine (NE) was reduced compared with that before treatment (P < 0.05). The level of each index did not change significantly before and after treatment in the control group (all P > 0.05). The regulations of 5-HT, GABA/Glu in the observation group were superior to those in the control group (all P < 0.05).

CONCLUSIONThe combined therapy of warm acupuncture and auricular point sticking method for warming yang and benefiting qi effectively improves brain neurotransmitters and essentially improves sleep quality of the patients with insomnia differentiated as yang deficiency pattern.

Acupuncture Points ; Acupuncture Therapy ; Acupuncture, Ear ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neurotransmitter Agents ; metabolism ; Serotonin ; metabolism ; Sleep Initiation and Maintenance Disorders ; metabolism ; therapy ; Treatment Outcome ; Yang Deficiency ; metabolism ; therapy ; Young Adult ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo explore the action mechanism of electroacupuncture (EA) at "Shenmen" (HT 7) and "Sanyinjiao" (SP 6) on insomnia.

METHODSThirty SD rats were randomly divided into a blank group, a model group and an EA group, 10 cases in each group. The insomnia model was made by immobilization method in the model group and EA group. After model establishment, rats in the blank group and model group were treated with fixation and no treatment was given. Rats in the EA group were treated with EA at "Shenmen" (HT 7) and "San-yinjiao" (SP 6) for 15 min, once a day for 4 days. After treatment, the level of daytime and nighttime activity, open-arm entry percentage and open-arm time percentage of elevated plus-maze test were measured; the content of noradrenaline (NE), dopamine (DA) and epinephrine (EPI) in plasma and NE, DA in thalamus and brainstem were detected by using euzymelinked immunosorbent assay method.

RESULTSCompared with the blank group, the daytime activity was increased and nighttime activity was reduced in the model group (both P<0. 05); the open-arm entry percentage and open-arm time percentage of elevated plus-maze test were both reduced in the model group (both P<0. 05); the contents of NE, DA, EPI in the plasma and NE, DA in thalamus and brainstem were increased in the model group (all P<0. 05). Compared with the model group, the daytime activity was reduced and nighttime activity was increased in the EA group (both P<0. 05); the open-arm entry percentage and open-arm time percentage of elevated plus-maze test were both increased in the EA group (both P<0. 05); the contents of NE, DA, EPI in the plasma and NE, DA in thalamus and brainstem were reduced in the EA group (all P< 0. 05).

CONCLUSIONElectroacupuncture at "Shenmen" (HT 7) and "Sanyinjiao" (SP 6) can restrain the over-activity of the sympathetic-adrenal medullary system to treat the insomnia.

Acupuncture Points ; Adrenal Medulla ; metabolism ; Animals ; Anxiety ; Disease Models, Animal ; Dopamine ; metabolism ; Electroacupuncture ; Female ; Humans ; Male ; Norepinephrine ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders ; metabolism ; physiopathology ; psychology ; therapy ; Sympathetic Nervous System ; physiopathology

OBJECTIVETo understand the action mechanism of Tianwang Buxin decoction that is the whole prescription included all drugs from Tianwang Buxin honeyed pill and Tianwang Buxin without radix platycodi decoction on the nerves-calming and hyposomnia-curing.

METHODThe influence of Tianwang Buxin decoction and Tianwang Buxin without radix platycodi decoction on somnus utilizing the mice' s somnus in coordination with Pentobarbital sodium was observed. Investigation whether the compatibility of radix platycodi affect the concentration of brain neurotransmitter, 5-HT, NA and DA, correlated sleep-awareness by HPLC-ECD detection was carried out after rats' hyposomnia model were founded.

RESULTThe falling asleep rates of mice given subthreshold dose raised (P<0.05), remarkably because of Tianwang Buxin decoction. But there is significant difference with Tianwang Buxin lack of radix platycodi decoction despite the heightening tendency. All groups were discovered that the level of 5-HT and 5-HIAA, the monoamine transmitter, heighten obviously after the whole prescription and the prescription without radix platycodi were administered in nuclei raphae medullae oblongatae (P<0.05), but it is only the whole prescription group that emerged same phenomenon in the Ammon's horn and striatum area. Furthermore significant difference exist as comparing Tianwang Buxin whole prescription decoction with Tianwang Buxin without radix platycodi decoction. The level of another monoamine transmitter DA stepped up notably in the whole prescription and the prescription without radix platycodi groups following administration in corpora striata (P<0.05).

CONCLUSIONThe mechanism of hypnosis action lie in enhancement of releasing 5-HT in encephalic regions for the Tianwang Buxin whole prescription decoction, but it's possible that radix platycodi may be the key point that adjusts the additional quantity.

Animals ; Brain ; drug effects ; metabolism ; Dose-Response Relationship, Drug ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Female ; Hippocampus ; drug effects ; metabolism ; Male ; Neostriatum ; drug effects ; metabolism ; Neurotransmitter Agents ; metabolism ; Rats ; Sleep Initiation and Maintenance Disorders ; drug therapy ; metabolism ; pathology