Integrative Medicine Research

Volume 3, Issue 2, June 2014, Pages 41–48

Open Access

Review Article

Research advances in treatment of neurological and psychological diseases by acupuncture at the Acupuncture Meridian Science Research Center

• Bombi Lee^a,
• Seung-Nam Kim^a,
• Hi-Joon Park^{a, b},
• Hyejung Lee^{a, b, ,}

Open Access funded by Korea Institute of Oriental Medicine

Under a Creative Commons license

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doi:10.1016/j.imr.2014.03.003

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Abstract

Acupuncture is an ancient therapeutic intervention that can be traced back at least 2100 years and is emerging worldwide as one of the most widely used therapies in the field of complementary and alternative medicine. Due to limitations associated with Western medicine's focus on the treatment of diseases rather than on their causes, interests are shifting to complementary and alternative medicines. The Acupuncture and Meridian Science Research Center (AMSRC) was established in 2005 to elucidate the neurophysiological mechanisms of acupuncture for neurological diseases based on multidisciplinary research supported by the Korean Ministry of Science and Technology. In the AMSRC, resultant research articles have shown that acupuncture can improve neurological and psychological problems, including Parkinson's disease, pain, and depression, in animal models. Basic research studies suggest its effectiveness in treating various problems such as depression, drug addiction, epilepsy, ischemia, dementia, Parkinson's disease, and pain. We strongly believe that these effects, evident from the AMSRC research results, can play leading roles in the use of acupuncture for treating neurological diseases, based on collaboration among various academic fields such as neurophysiology, molecular genetics, and traditional Korean medicine.

Keywords

• acupuncture therapy;
• depression;
• multidisciplinary research;
• neurological diseases;
• Parkinson's disease

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1. Introduction

Acupuncture has been practiced in China for more than 2100 years, and is a natural healing therapy that has gained increasing popularity and acceptance by the public and health care professionals worldwide. Acupuncture had been used in Korea long before it was introduced to Japan in the 6th century ad, and spread to Europe and North America during the 16th–19th centuries ad.¹ In 1971, a report by James Reston in the New York Times about his experience of acupuncture treatment in China exposed countless Americans to acupuncture for the first time. Since then, research on acupuncture has been conducted extensively worldwide.

Acupuncture is claimed to be an effective treatment against diseases, with wide applications. It has advantages of low cost and minimal side effects. Acupuncture has been used for hwa-byung or depression, as well as for treating chronic illnesses and injuries such as back pain, knee osteoarthritis, tension headache, migraine, nausea, and vomiting.^2 and 3 There is a current trend to expand the therapeutic scope of acupuncture to cosmetic treatment, diet, and plastic surgery.

However, basic research on the efficacy of acupuncture and its mechanisms of action is insufficient to systematize and objectify acupuncture therapy due to a lack of experimental approaches. Therefore, the efficacy of acupuncture is being investigated intensively in huge research programs to identify its various uses in Western countries.

Acupuncture needling can affect multiple systems in the body including the nervous system, immune system, and cardiovascular system, so more than one research method is necessary. The necessity for multidisciplinary research also arises due to the merits of both Western and Oriental medicines.

The Acupuncture and Meridian Science Research Center (AMSRC) at Kyung Hee University, Seoul, Korea, was opened in 2005, with support from the Korean Ministry of Science and Technology with the aim of conducting multidisciplinary research. The primary goal of the AMSRC is to establish a scientific basis for understanding the functional mechanisms of acupuncture and to investigate the therapeutic effectiveness of acupuncture for neurological diseases. According to the article “Global trends and performances of acupuncture research,” Kyung Hee University has been ranked, by the articles listed in Science Citation Index-Expanded, as a leader in the field of complementary and alternative medicine⁴ for the past 20 years, with contributions from the AMSRC. These research outcomes are a result of intensive efforts by Kyung Hee University to develop Korean medicine by identifying the value of traditional Korean medicine. The AMSRC brings scientific expertise and ancient traditional knowledge together in a comprehensive, translational, and integrated approach to identify the value of traditional Korean medicine.

Despite the dramatic development of Western medicine along with considerable advances in modern medicine, neurological diseases increase considerably with aging. Neurological diseases are defined as hereditary and sporadic conditions characterized by progressive nervous system dysfunction. Neurological diseases such as dementia and Parkinson's disease (PD) are burdensome from individual and social perspectives due to their poor prognosis. Thus, it is possible that acupuncture, with its rapid and broad therapeutic effects when applied clinically, is the appropriate therapeutic method for treating neurological diseases. A number of AMSRC researchers are studying the efficacy and mechanism of acupuncture for neurological diseases. These researches are intended to both examine the efficacy of acupuncture for neurological diseases and establish improved clinical research models for acupuncture therapy through multidisciplinary research.

In this review article, we summarize the findings of 4 years of research at the AMSRC aimed at exploring the effectiveness of acupuncture for neurological and other diseases and expanding the understanding of its functional mechanisms and therapeutic effectiveness.

1.1. Effects of acupuncture on depression and anxiety disorders

To develop an animal model that perfectly reproduces the symptoms of depression in patients, researchers at the AMSRC choose maternal separation (MS), exposure to chronic stress, and depression with chronic inflammation response in the rats or mice. First, Kim et al⁵ and Park et al⁶ conducted animal model experiments using MS as representative of an event that might cause a depressive disorder. Early stressors such as MS or social isolation can influence the development of biological and neurological systems and increase vulnerability to neurodegenerative diseases and psychiatric conditions such as depression and anxiety. Long-term consequences of stress due to MS usually appear as neurodegenerative changes in the brain and depressive-like behavior in a stress-dependent manner.⁷ A proteomic approach was used to express and identify new hypothalamic proteins in MS rats in an animal model to study early environmental insults.⁵ In a group with MS given acupuncture at acupoint Sobu (HT8), five proteins were downregulated and nine were upregulated, compared with the untreated MS group. Among the nine proteins upregulated by acupuncture treatment, Kim et al⁵ and Park et al⁶ found four to be related to neurodevelopment. Therefore, acupuncture at HT8 may affect neurodevelopment and be a possible therapy for neurodevelopmental disorders. Additionally, acupuncture at acupoint Shenmen (HT7) significantly increased the frequency of entry and the amount of time spent in the open arms in the elevated plus maze test, reduced plasma corticosterone (CORT) levels, and reduced arginine vasopressin expression in the hypothalamus of MS rats, suggesting that it may reduce anxiety-related behaviors and modulate activation of the hypothalamic–pituitary–adrenal (HPA) axis.⁶ In further studies, acupuncture at HT7 improved MS-induced depressive-like behaviors in the tail suspension test, normalized the 5-hydeoxyindole-3-acetic acid (5-HIAA)/serotonin (5-HT) ratio, alleviated serotonin transporter (5-HTT), and increased brain-derived neurotrophic factor (BDNF) reduction in the prefrontal cortex (Fig. 1).⁸ Although it remains elusive whether reduction of 5-HTT expression or restoration of the 5-HIAA/5-HT ratio by acupuncture stimulation is more crucial for improving these behaviors, it is obvious that acupuncture at HT7 alleviated MS-induced impairment of the 5-HT system in that study. The authors of these studies also suggested that the MS-induced changes in the 3,4-dihydroxyphenylacetic acid/dopamine (DA) ratio in the hippocampus and prefrontal cortex, and plasma CORT levels in MS rats were significantly alleviated after HT7 stimulation (Fig. 1).⁹ Based on the results of these and previous studies, the authors suggested that functional recovery of the prefrontal–limbic system by acupuncture stimulation plays an important role in the treatment of depression-like symptoms in MS rats.

Fig. 1. 

Effect of acupuncture on immobility time and expression of serotonin transporter of maternally-separated rat pups. (A) Immobility times of rat pups in the tail suspension test. (B) Expression of serotonin transporter (5-HTT) in the prefrontal cortex of rat pups.

^*p < 0.05.

^**p < 0.01 versus NOR group.

^##p < 0.01.

^###p < 0.001 versus MS group.

HT7, acupoint Shenmen; MS, maternally separated control group; MS + HT7, maternally separated group with acupuncture stimulation at HT7 acupoint; MS + ST36, maternally separated group with acupuncture stimulation at ST36; NOR, normal group; ST36, acupoint Zusanil.

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Second, chronic stress results in dysregulation of the HPA axis in the neuroendocrine system, as evidenced by observations that the elevation of circulating CORT levels disrupts the circadian regulation of CORT secretion as well as the glucocorticoid receptor-negative feedback circuit.¹⁰ Activation of the HPA axis by high-dose CORT administration is associated with the development of psychic-related disorders, such as depression and anxiety, in rats.¹¹ Lee et al¹² reported that acupuncture stimulation at acupoint Neiguan (PC6) significantly reduced chronic CORT-induced depression and anxiety-like behaviors, and increased neuropeptide Y expression in the hypothalamus. That study suggested that acupuncture may be an effective treatment for stress-related disorders such as depression and anxiety, probably by modulating the HPA axis.

Third, gradual and continuous experimental inoculation of mice with Bacillus Calmette–Guerin (BCG) vaccine elicited chronic inflammation-associated depressive-like behavior.¹³ Acupuncture stimulation at Sanyinjiao (SP6) had antidepressant-like effects in a murine depression-like behavior model following chronic systemic inflammation/immune response induced by BCG inoculation by modulating the aggravated tryptophan–kynurenine metabolism pathway and dopaminergic neurotransmission in the hippocampus.¹³ These results support the possibility that acupuncture has antidepressant and anxiolytic effects.

1.2. Effects of acupuncture on drug addiction

The AMSRC researchers have explored repeated administration of three kinds of psychostimulant drugs, including cocaine, nicotine, and morphine, to establish drug addiction in the animal model. Abuse of drugs such as cocaine, nicotine, amphetamine, and morphine and their subsequent withdrawal cause a negative emotional state and psychiatric side effects, including depression and anxiety.¹⁴ Many studies have demonstrated that drug withdrawal causes depressive- and anxiety-related symptoms in humans and corresponding behavioral responses in animals.¹⁵ Chae et al¹⁶ reported that increases in the corticotrophin-releasing factor may be involved in the negative emotional state associated with nicotine withdrawal, and acupuncture at HT7 may attenuate anxiety-like behavior following nicotine withdrawal by modulating corticotrophin-releasing factor in the amygdala. Repeated administration of various psychoactive substances, including cocaine and morphine, can produce a more robust effect than the first dose alone, even after an abstinence period.¹⁷ This phenomenon, called behavioral sensitization, may play an important role in the development of drug addiction and drug-induced psychosis, as evidenced by an enhanced locomotor response to a subsequent injection of the drug.¹⁸ Many studies suggest that the development and expression of behavioral sensitization due to repeated cocaine or morphine exposure are related to an elevation in DA neurotransmission.¹⁹ The authors clearly showed that treatment with acupuncture at the HT7 point significantly suppressed repeated cocaine-induced behavioral sensitization and increased tyrosine hydroxylase expression in the ventral tegmental area of the central dopaminergic pathways.²⁰ Repeated morphine-induced behavioral sensitization is closely associated with the overexpression of DA biosynthesis and its activity in the postsynaptic neurons in the nucleus accumbens of the central DA pathway.²¹ Acupuncture stimulation has an acupoint-specific property that may be useful as a therapeutic alternative with few side effects for treating addiction to drugs such as nicotine, cocaine, and morphine.

1.3. Effects of acupuncture on chronic intractable epilepsy

Epilepsy is one of the most common and devastating neurological diseases characterized by seizures, and its prognosis is not good among the grave symptoms of a serious brain disease.²² The AMSRC researchers have suggested that intracerebral injection of kainic acid (KA) in the hippocampus or amygdala in rats could represent a model of temporal lobe epilepsy, because it reproduced the typical histopathological changes seen in epileptic patients.²² Kim et al²³ reported that acupuncture inhibits KA-induced epileptic seizures and hippocampal cell death by increasing glutamate decarboxylase-67 expression. Acupuncture at HT8 reduced the severity of KA-induced epileptic seizures and the rate of neural cell death; it also decreased expression of c-Fos and c-Jun induced by KA in the hippocampus, as shown by immunohistochemistry and Western blotting. In further research, acupuncture stimulation at HT8 suppressed KA-induced microglia activation and expression of proinflammatory cytokine, such as interleukin (IL)-1β, in the hippocampus.²⁴ These results suggest that acupuncture exhibits a variety of neuromodulatory functions in patients with epileptic seizures, such as regulating neuronal gene expression and proinflammatory cytokines.

1.4. Effect of acupuncture on cerebral ischemia

Cell proliferation and apoptosis from ischemia in the hippocampus can effectively be improved by acupuncture. Increased cell proliferation in the dentate gyrus of the hippocampus following cerebral ischemia is a compensatory response to ischemia-induced increased apoptosis in gerbils via 5-bromo-2′-deoxyuridine immunohistochemistry, and it is possible that acupuncture at the Zusanil (ST36) and Ho-Ku (LI4) acupoints plays an important role in the regulation of cell proliferation and apoptosis following ischemic injury.²⁵ Intracerebral hemorrhage-induced Fos expression and cell proliferation in the dentate gyrus of rats following acupuncture treatment at the ST36 acupoint has also been investigated.²⁶ Thus, acupuncture treatment alleviates ischemia-induced apoptosis and cell proliferation, and holds possible therapeutic potential for recovery following stroke.

1.5. Effect of acupuncture on dementia

Acupuncture stimulation at the PC6 point is effective in restoring chronic mild stress-induced behavioral impairments, such as impaired learning and memory, in the Morris water maze test, and increased acetylcholinesterase reactivity in the hippocampus.²⁷ Acupuncture significantly alleviated memory-associated decreases in cholinergic immunoreactivity and BDNF and cyclic adenosine monophosphate-response element-binding protein (CREB) mRNA expression in the hippocampus of rats following repeated exposure to exogenous CORT in the Morris water maze test.²⁸ Attenuation of memory and cognitive impairments by acupuncture stimulation may be due to restoration of cholinergic neurochemical abnormalities and regulation of BDNF and CREB expression. It is likely that acupuncture as an alternative therapy can improve chronic stress-induced memory deficit symptoms by modulating the HPA axis and can retard the progression of memory deficits in patients with neurodegenerative disease.