The mechanism of acupuncture and clinical applications

This study presents the result of the studies explaining the effects of acupuncture on various systems and symptoms. It has been determined that endomorphin-1, beta endorphin, encephalin, and serotonin levels increase in plasma and brain tissue through acupuncture application. It has been observed that the increases of endomorphin-1, beta endorphin, encephalin, serotonin, and dopamine cause analgesia, sedation, and recovery in motor functions. They also have immunomodulator effects on the immune system and lipolithic effects on metabolism. Because of these effects, acupuncture is used in the treatment of pain syndrome illnesses such as migraine, fibromyalgia, osteoarthritis, and trigeminal neuralgia; of gastrointestinal disorders such as disturbance at gastrointestinal motility and gastritis; of psychological illnesses such as depression, anxiety, and panic attack; and in rehabilitation from hemiplegia and obesity.     

A NEW EXTRA-VERTEBRAL TREATMENT MODEL FOR INCOMPLETE SPINAL CORD INJURIES

The present study is an investigation of the results of the studies on the effects of acupuncture application therapy on obesity. It has been reported that acupuncture application in obesity treatment is effective in procuring weight loss. It can affect appetite, intestinal motility, and metabolism, as well as emotional factors such as stress. Increases in neural activity in the ventromedial nuclei of the hypothalamus, in tone in the smooth muscle of the stomach and in levels of enkephalin, beta endorphin, and serotonin in plasma and brain tissue have also been observed with the application of acupuncture. It has been observed that acupuncture application to obese people increases excitability of the satiety center in the ventromedial nuclei of the hypothalamus. Acupuncture stimulates the auricular branch of the vagal nerve and raises serotonin levels. Both of these activities have been shown to increase tone in the smooth muscle of the stomach, thus suppressing appetite. Among other things, serotonin enhances intestinal motility. It also controls stress and depression via endorphin and dopamine production. In addition to these effects, it is thought that the increase in plasma levels of beta endorphin after acupuncture application can contribute to the body weight loss in obese people by mobilizing the body energy depots through lipolithic effect.     

The treatment of obesity by acupuncture

The present study is an investigation of the results of the studies on the effects of acupuncture application therapy on obesity. It has been reported that acupuncture application in obesity treatment is effective in procuring weight loss. It can affect appetite, intestinal motility, and metabolism, as well as emotional factors such as stress. Increases in neural activity in the ventromedial nuclei of the hypothalamus, in tone in the smooth muscle of the stomach and in levels of enkephalin, beta endorphin, and serotonin in plasma and brain tissue have also been observed with the application of acupuncture. It has been observed that acupuncture application to obese people increases excitability of the satiety center in the ventromedial nuclei of the hypothalamus. Acupuncture stimulates the auricular branch of the vagal nerve and raises serotonin levels. Both of these activities have been shown to increase tone in the smooth muscle of the stomach, thus suppressing appetite. Among other things, serotonin enhances intestinal motility. It also controls stress and depression via endorphin and dopamine production. In addition to these effects, it is thought that the increase in plasma levels of beta endorphin after acupuncture application can contribute to the body weight loss in obese people by mobilizing the body energy depots through lipolithic effect.     

Smoking cessation after acupuncture treatment

Acupuncture is applied, especially in treatment of pain, hemiplegia, obesity, and psychological illnesses including addiction. Recently, ear and body acupuncture have been frequently used in the treatment of smoking. An increase in levels of endorphin, enkephalin, epinephrine, norepinephrine, serotonin, and dopamine in the central nervous system and plasma has been reported as the most important mechanism of acupuncture. That is, acupuncture application may increase the levels of endorphin, enkephalin, epinephrine, norepinephrine, serotonin, and dopamine in the central nervous system and plasma. The authors think that acupuncture application provides the patients with deterioration in the taste of smoking, decrease in desire of smoking, and the obstruction of psychological symptoms that appear as a result of smoking cessation. Because of these effects it is presumed that acupuncture application may be used as an important method for smoking cessation treatment.     

SMOKING CESSATION AFTER ACUPUNCTURE TREATMENT

Acupuncture is applied, especially in treatment of pain, hemiplegia, obesity, and psychological illnesses including addiction. Recently, ear and body acupuncture have been frequently used in the treatment of smoking. An increase in levels of endorphin, enkephalin, epinephrine, norepinephrine, serotonin, and dopamine in the central nervous system and plasma has been reported as the most important mechanism of acupuncture. That is, acupuncture application may increase the levels of endorphin, enkephalin, epinephrine, norepinephrine, serotonin, and dopamine in the central nervous system and plasma. The authors think that acupuncture application provides the patients with deterioration in the taste of smoking, decrease in desire of smoking, and the obstruction of psychological symptoms that appear as a result of smoking cessation. Because of these effects it is presumed that acupuncture application may be used as an important method for smoking cessation treatment.     

Delayed pharmacological effects of antidepressants

Although antidepressants may not be primary mood stabilizers, they are efficacious in the prophylaxis of recurrent depressive illnesses, as well as in the treatment of acute episodes. Pharmacological effects that may contribute to the prophylactic effects of these drugs are not understood. Studies have been carried out in which antidepressants have been given to laboratory animals, such as rats, for periods of up to 3-4 weeks. Data obtained in such studies are thought to be important for their beneficial effects in depressive episodes, but also may be relevant to their prophylactic effects. Results are presented showing that when selective inhibitors of serotonin or norepinephrine uptake are given for such time periods, they still produce selective effects on serotonergic or noradrenergic parameters. For example, long-term administration of selective norepinephrine reuptake inhibitors causes a down-regulation of beta(1) adrenoceptors. Selective serotonin reuptake inhibitors do not produce this effect. Long-term administration of selective serotonin reuptake inhibitors causes down-regulation of the serotonin transporter, but not the norepinephrine transporter. In contrast, selective norepinephrine reuptake inhibitors down-regulate the norepinephrine transporter but not the serotonin transporter. Substantial loss of serotonin transporter binding sites takes 15 days to occur and is accompanied by a marked reduction of serotonin transporter function in vivo.     

Acupuncture for Schizophrenia

Background

Acupuncture, with many categories such as traditional acupuncture, electroacupuncture, laser acupuncture, and acupoint injection, has been shown to be relatively safe with few adverse effects. It is accessible and inexpensive, at least in China, and is likely to be widely used there for psychotic symptoms.

Objectives

To review the effects of acupuncture, alone or in combination treatments compared with placebo (or no treatment) or any other treatments for people with schizophrenia or related psychoses.Search MethodsWe searched the Cochrane Schizophrenia Group Trials Register (February 2012) and inspected references of all identified studies. We contacted relevant authors for additional information.

Selection Criteria

We included all relevant randomized controlled trials involving people with schizophrenia-like illnesses, comparing acupuncture added to standard dose antipsychotics with standard dose antipsychotics alone, acupuncture added to low dose antipsychotics with standard dose antipsychotics, acupuncture with antipsychotics, acupuncture added to traditional chinese medicine (TCM) drug with TCM drug, acupuncture with TCM drug, electric acupuncture convulsive therapy with electroconvulsive therapy.     

Acupuncture ameliorates not only atopic dermatitis-like skin inflammation but also acute and chronic serotonergic itch possibly through blockade of 5-HT2 and 5-HT7 receptors in mice

Acupuncture has been known to be effective for atopic dermatitis, especially ameliorating itch; however, its mechanisms are still unclear. The aim of this study was to test the anti-itch effects of acupuncture and to investigate its possible mechanisms. Acupuncture was performed at Gok-Ji (LI11) acupoints just before the injection of pruritogens in the mouse cheek model of acute itch and of MC903-induced atopic dermatitis displaying serotonergic chronic itch. Acupuncture significantly reduced acute itch triggered by compound 48/80, chloroquine, or especially serotonin. It also markedly reduced scratching behaviors evoked by the serotonin 5-HT₂ receptor agonist α-methylserotonin and selective 5-HT₇ receptor agonist LP 44. In addition, acupuncture treatment at LI11 had the preventive and therapeutic effects on persistent itch as well as the robust skin inflammation with epidermal thickening in mice with MC903-induced atopic dermatitis. It also considerably reduced the increased expression of 5-HT_2A, 5-HT_2B and 5-HT₇ receptors in atopic dermatitis-like skin lesions in mice treated with MC903. Taken together, these findings highlight that acupuncture significantly ameliorates not only skin inflammation, but also acute and chronic serotonergic itch, possibly through blockade of serotonin 5-HT₂ and 5-HT₇ receptors.     

Changes in endorphins and 5-hydroxyindoleacetic acid in cerebrospinal fluid as a result of treatment with a serotonin reuptake inhibitor (zimelidine) in chronic pain patients

Both the endorphin and the serotonin systems seem to be involved in pain perception, and a significant positive correlation between the levels of endorphins and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) has been established. In the present study, 20 chronic pain patients were treated with zimelidine, a rather selective inhibitor of serotonin reuptake, or placebo. Zimelidine produced a significant pain relief and a significant reduction of the levels of endorphins and 5-HIAA in CSF, while no significant changes occurred during placebo treatment. The results indicate that both the endorphin and the serotonin systems are involved in pain perception and that the systems are functionally related.     

Effect of Acupuncture on the Motor and Nonmotor Symptoms in Parkinson's Disease—A Review of Clinical Studies

Parkinson's disease is a neurodegenerative disorder. Parkinson's clinical feature is characterized by its motor manifestations, although its many nonmotor symptoms occur earlier and have more profound impact on the quality of patient's life. Acupuncture has been increasingly popular and has been used to treat patients with Parkinson's. In this article, we have studied the clinical reports of acupuncture treatment for Parkinson's, which were listed in Medline, PubMed, EMBASE, CNKI, and CINAHL databases in the past 15 years. It was found that acupuncture either manual or electroacupuncture stimulation at specific acupoints relieved some motor symptoms in patients with Parkinson's and markedly improved many nonmotor symptoms such as psychiatric disorders, sleep problems, and gastrointestinal symptoms. When it was used as an adjunct for levodopa, acupuncture improved therapeutic efficacy and reduced dosage and the occurrence of side effects of levodopa. However, the results were constrained by small sample sizes, methodological flaws, and blinding methods of studies. Although the evidence for the effectiveness of acupuncture for treating Parkinson's is inconclusive, therapeutic potential of acupuncture seems quite promising. More studies, either comparative effectiveness research or high‐quality placebo‐controlled clinical studies are warranted.     

Acupuncture inhibits neuroinflammation and gut microbial dysbiosis in a mouse model of Parkinson’s disease

Growing evidences show that gut microbiota is associated with the pathogenesis of Parkinson’s disease (PD) and the gut-brain axis can be promising target for the development of the therapeutic strategies for PD. Acupuncture has been used to improve brain functions and inflammation in neurological disorders such as PD, and to recover the gastrointestinal dysfunctions in various gastrointestinal disorders. Thus, we investigated whether acupuncture could improve Parkinsonism and gut microbial dysbiosis induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. First, we observed that acupuncture treatment at acupoints GB34 and ST36 could improve motor functions and comorbid anxiety in PD mice. Next, we found that acupuncture increased the levels of dopaminergic fibers and neurons in the striatum and the substantia nigra, respectively. Acupuncture also restored the overexpression of microglia and astrocyte as well as conversion of Bax and Bcl-2 expression in both the striatum and the substantia nigra, indicating that inflammatory responses and apoptosis were blocked by acupuncture. Additionally, via 16S rRNA sequence analysis, we observed that the relative abundance of 18 genera were changed in acupuncture-treated mice compared to the PD mice. Of them, Butyricimonas, Holdemania, Frisingicoccus, Gracilibacter, Phocea, and Aestuariispira showed significant correlations with anxiety as well as motor functions. Furthermore, the predicted functional analyses showed that acupuncture restored the physiology functions such as glutathione metabolism, methane metabolism, and PD pathway. In conclusion, we suggest that the effects of acupuncture on the enhanced motor function and the protection of the dopaminergic neurons may be associated with the regulation of the gut microbial dysbiosis and thus the inhibition of the neuroinflammation in the PD mice.     

Neurobiology of learning--the basis of an alteration process

In contrast to the opinion that prevailed in the 1980es, there is now increasing evidence that the plasticity of the human brain, i. e. its remarkable ability to adapt to and change with experience, is, under normal conditions, a lifelong phenomenon. Representations of the environment are associated with activations and biochemical modifications in neuronal networks, which will be stabilized, modified or will wither in the course of cumulated experience. The capability to modify the biochemistry of synapses as well as the growth and change in terms of rewiring of synapses, dendritic branching and glial cell proliferation via the dialogue of synapses and genes, results in specific changes in neuronal connectivity and function. On the neurotransmitter level, glutamate and gamma-amino-butyric acid (GABA) as well as dopamine and serotonin, but also endorphin and encephalin, have a key position in this context. These neurotransmitter systems modulate neuronal plasticity on the neuronal level; on the behavioural level they influence affect, emotion, positive motivation and the correct evaluation of environmental stimuli. Experience, action as well as learning and memory are influenced by these systems. A basic thesis of this paper is that these mechanisms are involved in neuronal plasticity and that learning and memory are thus not only used and reused in structuring the CNS during the initial establishment of connections in the immature brain, in lifelong memory consolidation or the rewiring after brain damage, but can also be used to mould experience, learning und behaviour during psychotherapy and rehabilitation in adults.     

抑郁症的神经内分泌学初步研究

目的：研究抑郁症的血浆β-内啡肽及其他神经内分泌改变。方法：采用放射免疫法对抑郁症患者的血浆β-内啡肽及其他神经内分泌进行测定，并与正常人对照。结果：患者组的β-内啡肽（β-EP）,生长抑素（SS），肿瘤坏死因子（TNF），白细胞介素-8（IL-8），白细胞介素-10（IL-10）明显高于对照组，女性白细胞介素-6（IL-6）高于对照组，生长激素（GH）低于对照组，促肾上腺皮质激素（ACTH），促肾上腺皮质激素释放激素（CRH），催乳素（PRL），神经肽Y（NPY），白细胞介素-1（IL-1），白细胞介素-2（IL-2），白细胞介素-4（IL-4），两组无差异。结论：抑郁症存在血浆β-内啡肽及其他神经内分泌异常。     

Endorphin research in schizophrenic psychoses

The discovery of the endorphins has opened up a new dimension for research into the biological determinants of schizophrenic behavior. However, it would be premature to advance an endorphin hypothesis on the pathogenesis of schizophrenic psychoses at this time. Technical difficulties have so far been an obstacle in the study of the human central endorphin metabolism. The therapeutic aspect of endorphin research shows some interesting features. Opiate (endorphin) antagonists certainly do not seem to be universal antipsychotics, but undoubtedly it is worthwhile to continue the search for subgroups that are susceptible to these compounds. The reverse of this strategy has also been applied: administration of endorphins to schizophrenic patients. Of the three compounds used in this context, β-endorphin, a synthetic met-enkephalin derivative and DTγE, the latter is the most interesting. It is a naturally occurring fragment of γ-endorphin which lacks morphinomimetic effects and has certain pharmacological as well as clinical properties in common with the traditional neuroleptics. This compound may well open up entirely new perspectives for the treatment of schizophrenic psychoses.     

Is the brain hormonally imprintable?

Hormonal imprinting develops at the first encounter between the target hormone and its developing receptor in the perinatal critical period. This determines the binding and response capacity of the receptor-signal transduction system and hormone production of cells for life. Molecules similar to the hormone and excess or absence of the target hormone cause faulty imprinting with lifelong consequences. Prenatal or neonatal imprinting with opiates, other drugs and prenatal stress have harmful consequences on the adult brain. Perinatal imprinting with endorphin or serotonin decreases the serotonin level of the brain while increasing sexual activity and (as in the case of endorphin) aggression. Endorphin or serotonin antagonist treatment at weaning (late imprinting) also significantly reduces the serotonin content of the brain. Backed by literary data, these observations are discussed, and the possible consequences of medical treatments are shown. The paper concludes that an excess of molecules produced by the brain itself can provoke perinatal imprinting, and it points to the possibility of late imprinting of the brain by receptor level acting agents, including a brain product (endorphin).     

Mechanism of Acupuncture on Neuromodulation in the Gut—A Review

Introduction: Acupuncture has been used for treating various gastrointestinal (GI) diseases. However, the mechanism of acupuncture remains unclear. Methods: The aim of this article is to review the published literature on the mechanism of acupuncture on neuromodulation in the gut. Results: Acupuncture treatment involves the insertion of thin needles into the skin and underlying muscle and the subsequent stimulation of the needles manually or electrically. Thus, acupuncture stimulates the somatic afferent nerves of the skin and muscles. The somatic sensory information from the body is carried to the cortex area of the brain. Somatic sensory fibers also project to the various nuclei at the brain stem and hypothalamus. Via somato‐autonomic reflex, acupuncture modulates various biomechanical responses, such as prokinetic, antiemetic, and anti‐nociceptive effects. Conclusion: According to traditional Chinese medicine, “Acupuncture is believed to restore the balance of Yin and Yang.” This can be translated into the Western medicine terminology that “Acupuncture modulates the imbalance between the parasympathetic and sympathetic activity.” Acupuncture may be effective in patients with functional GI disorders because of its effects on GI motility and visceral pain.     

Long-lasting cardiovascular depressor response following sciatic stimulation in spontaneously hypertensive rats. Evidence for the involvement of central endorphin and serotonin systems

A naloxone-reversible long-lasting depressor response induced by a prolonged low frequency stimulation of the sciatic nerve in conscious spontaneously hypertensive rats (SHRs) was reported in a previous paper. In the present study pharmacological tools were used to further investigate the neurotransmitters involved in this phenomenon. Naloxone infusion (20–25 mg/kg/h following a bolus dose of 10 mg/kg i.v.) attenuated significantly the depressor response, while dexamethasone pretreatment had no such effect, suggesting an important role of the brain endorphin system, but not of the pituitary β-endorphin, in this depressor response. Since the concomitant increase in pain threshold produced by the sciatic stimulation exhibited a different time course of development and naloxone reversibility, it is suggested that the depressor response and the hypalgesic effect produced by the same stimulation are mediated via different types of opiate receptors in the brain. On the other hand, PCPA abolished the post-stimulatory depressor response whereas 5-HTP and zimelidine had additive effects on the sciatic stimulation-induced depressor response, suggesting the involvement of central serotonin systems in the mechanism of the response. The interaction between the central endorphin and the serotonin systems in the mediation of the post-stimulatory depressor response is discussed.     

Beta endorphin concentrations in PBMC of patients with different clinical phenotypes of multiple sclerosis

The possible link between the opioid peptide beta endorphin and the heterogeneity of the clinical course of multiple sclerosis (MS) was investigated. Peripheral blood mononuclear cells (PBMC) concentrations of beta endorphin were measured in 50 patients in different phases of MS. Thirty nine patients also underwent post-contrast magnetic resonance imaging of the brain. Among MS forms, the highest beta endorphin concentrations were found in PBMC from patients with relapsing remitting MS and the lowest in patients with the progressive forms. Average beta endorphin concentrations were lower, although not significantly, in patients with than in those without magnetic resonance imaging enhanced lesions. These data suggest that beta endorphin may have a role in the downregulation of the inflammatory process.     

Immunohistochemical localization of endomorphin-1 and endomorphin-2 in immune cells and spinal cord in a model of inflammatory pain

Recently, two novel highly selective mu-opioid receptor (MOR) agonists, endomorphin-1 and endomorphin-2, have been isolated from bovine as well as human brains and were proposed to be the endogenous ligand for MOR. Later, endomorphin-1 and endomorphin-2 have been detected in the immune system of rats and humans using radioimmunoassay in combination with reverse-high-phase-liquid chromatography. In the present study, we analyzed the expression of endomorphin-1, endomorphin-2 and MOR by immunohistochemistry in a model of Freund's complete adjuvant (FCA)-induced painful inflammation. While MOR was upregulated on peripheral and central nerve terminals, inflammation did not alter endomorphin-2 expression in nerve fibers either in the dorsal horn of the spinal cord or in subcutaneous tissue. Endomorphin-1 and endomorphin-2 were expressed in immune cells (macrophage/monocytes) in the medullary region of the popliteal lymph nodes. The proportion of immunocytes (macrophage/monocytes, lymphocytes) containing endomorphin-1 and endomorphin-2 was increased in inflamed lymph nodes and subcutaneous paw tissue of animals with local inflammatory pain. Taken together, the upregulation of MOR and of its endogenous ligands endomorphin-1 and endomorphin-2 in immunocytes suggests an involvement of these opioid peptides in the peripheral control of inflammatory pain.     

Capsaicin inhibits the in vitro binding of peptides selective for mu- and kappa-opioid, and nociceptin-receptors

Capsaicin inhibited the equilibrium specific binding of endogenous opioid-like peptide ligands such as endomorphin-1, nociceptin, and dynorphin((1-17)) in rat brain membrane preparations. We studied the in vitro effect of capsaicin (1-10 microM) on homologous and heterologous competitive binding of opioid ligands, using unlabeled synthetic peptides and the following tritiated compounds: [(3)H]endomorphin-1, [(3)H]endomorphin-2, [(3)H]nociceptin((1-17)) and [(3)H]dynorphin((1-17)). Capsaicin-dependent inhibition was also observed in [(35)S]GTPgammaS stimulation assays in the presence of certain opioid peptides. The inhibition of opioid binding was further investigated using other synthetic and natural mu-opioid ligands such as [D-Ala(2),(NMe)Phe(4),Gly(5)-ol]enkephalin (DAMGO), morphine and naloxone. The decrease in opioid ligand affinity upon capsaicin treatments was most apparent with endomorphin-1, followed by nociceptin and dynorphin. The binding of other investigated opioids were not affected in the presence of capsaicin. In [(3)H]endomorphin-1 binding assays, capsazepine antagonized the inhibitory effect of capsaicin in rat brain membranes suggesting the involvement of TRPV1 receptors. In Chinese hamster ovary (CHO) cells stably expressing mu-opioid receptors, but lacking vanilloid receptors, the inhibition by capsaicin on the binding of [(3)H]endomorphin-1 was not present. It is concluded that the inhibitory effect of capsaicin on the receptor binding affinity of endogenous opioid peptides in brain membrane preparations seems not to be a direct effect, it is rather a negative feedback interaction with opioid receptors.