Research progress of acupuncture in the treatment of Parkinson's disease

Lin-Jing Wang ,Jia-Shuai Li ,Xue Wang ,Ji-Yao Zhang ,Lu-Wen Zhu＊

1The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150001,China.2Heilongjiang University of Chinese Medicine,Harbin 150010,China.

Abstract Parkinson's disease (PD) is a common degenerative disease of the central nervous system.The basic and clinical research of acupuncture therapy has witnessed several advances in the treatment of PD.The purpose of this study is to provide some ideas for clinical acupuncture therapy in the treatment of PD.The authors attempt to achieve this objective by systematically organizing the clinical efficacy studies of several acupuncture therapies for PD and elaborating the mechanisms of action in terms of secretion of substantia nigra dopaminergic neurons,level of oxidative stress,inflammatory response,excitotoxicity,and mitochondrial dysfunction.

Keywords:Acupuncture,Parkinson's disease,Clinical research,Mechanism of action

Background

Parkinson's disease (PD) is a common degenerative disease of the central nervous system in the elderly population.It is characterized by [1] static tremors,myotonia,bradykinesia,abnormal posture,and gait.The core pathological mechanism of PD is that degeneration or necrosis of dopaminergic neurons in the mesencephalic substantia nigra leads to a considerable reduction of the striatum dopamine content.Presently,the primary treatment of PD is dopamine substitution therapy; however,after its long-term use,its efficacy is reduced and adverse reactions are increased [2].Acupuncture therapy such as the scalp,eye,abdominal,and body acupunctures have played essential roles in the rehabilitation of patients with PD.It can improve PD symptoms,reduce adverse drug reactions,prevent the progression of disease,and improve the quality of patients'life[3].

Clinical research of acupuncture in the treatment of PD

Scalp acupuncture therapy

Scalp acupuncture is a therapy for brain-derived diseases wherein thin needles are inserted into certain specific stimulation points,such as regions,bands,and acupoints,on the head.“Miraculous Pivot·Discussion on Seas” states:“The brain is the sea of marrow,its infusing acupoints are the one located in the vertex in the upper region and Fengfu in the lower region.”Thus,the scalp and its deep tissues,as the “cover” can be used as crucial pathways of body surface for the stimulation and regulation of the brain marrow's function [4].It is quite evident that scalp acupuncture is based on the viscera and meridians theory of the traditional Chinese medicine,as well as the localization of cerebral cortical function in modern anatomy.Needles inserted into the scalp cause stimulations,which further treat several brain diseases[5].

The clinical effect of scalp acupuncture in the treatment of PD is worthy of affirmation.Liu Dan et al.[6] treated 30 patients with PD by employing scalp acupuncture in the choreiform tremor control region combined with the oral administration of benserazide and levodopa tablets.The choreiform tremor control region was positioned in a 1.5 cm wide parallel band in front of the body surface projection of the head motor region.A filiform needle was inserted in horizontal or oblique position and left there for 1 hour and six times a week,during the 4 weeks as a course of treatment.After three courses of treatment,the Webster score of the treatment group was significantly lower than that of the control group receiving single and oral administration of benserazide and levodopa tablets.The treatment group had an effective rate of 93.30%,which was higher than 83.30% of the control group.Suo Qingfang et al.[7] used madopar combined with electro-nape and electro-scalp acupuncture for treating PD.Nape acupuncture took the bilateral Fengchi (GB 20),whereas scalp acupuncture took the choreiform tremor region (bilateral).The electroacupuncture device was turned on in the treatment group and the rarefaction wave was chosen for six times a week,during the two weeks as a course of treatment.After two courses,the unified Parkinson's disease rating scale (UPDRS)score and Webster score of the patients were lower than before treatment,and the descending range was more obvious than that of oral madopar alone,which suggested that the combination of electro-scalp and electro-nape acupuncture is more effective than oral drugs alone in treating PD.In addition,Ren Hongyu [8] took acupoints,such as Taichong (LR 3),Baihui (DU 20),Hegu (LI 4),Fengchi (GB 20),as the primary acupoints and took the governor meridian as the main channel,combined with dialectical matching acupoints,thereby making a certain experience summary for the acupoint selection treatment of PD.

Eye acupuncture therapy

Eye acupuncture belongs to a kind of microneedle therapy.It is based on recognizing diseases by eye observation.The position,morphology,and color of the veins are the primary points of recognizing diseases by eye observation.Each viscus has a corresponding region on eyes.Acupuncture at marginal acupoints can treat diseases of the corresponding organs [9].Jiang Hong et al.[10] combined oral administration of madopar and scalp acupuncture to treat PD in combination with eye acupuncture.They took the upper and lower energizer,liver,kidney,spleen,lung,and large intestine acupoints of the outer orbital regions of binoculus.They inserted needles at the oblique position along the subcutaneous tissue at 15°,and the needles were retained for 30 minutes and five times a week,during the four weeks as a course of treatment.After the first course of treatment,the elderly tremor syndrome dysfunction scores and UPDRS scores of patients with PD in the eye acupuncture group showed better results than those in the treatment group.Hu Xiaodong et al.[11]compared the treatment effects of eye acupuncture and scalp and body acupuncture on patients with PD.Among them,scalp and body acupuncture took Shuigou (DU 26),Baihui (DU 20),Dazhui (DU 14),Fengfu (DU 16),Hegu (LI 4),Taichong (LR 3),Taixi (KI 3),Zusanli(ST 36),Sanyinjiao (SP 6),and Hegu (LI 4) acupoints for purgation method,whereas the other points were taken for the even movement method.Eye acupuncture took the bilateral hepatic and renal regions.Upper energizer region (affected hemisphere) was added when the head and face exhibited abnormal expressions and tremors; middle energizer region(affected hemisphere)was added when the upper limbs showed tremors or uncoordinated movements; lower energizer region (affected hemisphere) was added when the lower limbs showed tremors or (and)bradykinesia or (and) abnormal posture and gait.The course of treatment lasted for 10 days.After six courses,patients in the treatment group showed a significant improvement in handwriting,muscle rigidity,tremor,facial expressions,language,and self-care ability of daily living than the control group,with a total effective rate of 93.30%.In addition,Feng Yuegui[12]deployed eyes acupuncture combined with oral administration of madopar in the treatment of patients with PD can significantly improve patients'hand movements,myotonia,facial expressions,language,and self-care ability of daily living.

Abdominal acupuncture therapy

Abdominal acupuncture refers to a brand-new type of acupuncture therapy that adjusts functional activities of vital energy and the Yin Yang,realizes the dynamic balance of Yin Yang of the human body,and treats systemic diseases by acupuncture at specific acupoints in the abdomen.Chen Xiuhua et al.[13] adopted oral administration of madopar along with abdominal acupuncture to treat 30 patients with PD.The main acupoints were Zhongwan (RN 12),Xiawan (RN 10),Qihai (BL 24),Guanyuan (BL 26),Qixue (KI 13),Shangqu (KI 17),and Huaroumen (ST 24).Bo's abdominal acupuncture was administrated once in a day for 10 days as a course of treatment.Moreover,the Webster score was used as the criterion for efficacy.After three courses,the abdominal acupuncture group presented a higher total effective rate than the control group with mild side effects and considerable differences in reducing gastrointestinal symptoms and on-off phenomenon.Wen Xing et al.[14] adopted abdominal acupuncture combined with oral administration of moxibustion and madopar tablets in patients with PD,in which the abdominal acupuncture selected the following acupoints:“Yin Qi Gui Yuan”(Zhongwan (RN 12),Xiawan (RN 10),Qihai (BL 24),Guanyuan (BL 26)),bilateral Shangqu (KI 17),bilateral Huaroumen(ST 24),and bilateral Wailing(ST 26).After 3 months of treatment,the difference in daily activity integral and total scores in the UPDRS of the treatment group improved significantly (P＜0.05)than the control group taking the oral administration of madopar.It suggested that abdominal acupuncture for PD could improve the survival quality of patients with PD through an overall adjustment of various visceral disorders,improvement of blood supply to the brain,and reduction of limb stiffness.

Scalp and body acupuncture therapy

The method of combining scalp acupuncture and body acupuncture to enhance the clinical treatment effect is referred to as “scalp and body acupuncture therapy” in short.Li Guangshang et al.[15] used oral administration of madopar plus scalp and body acupuncture in patients with PD.Bilateral parietal temporal anterior oblique lines were taken for scalp acupuncture,whereas Quchi(LI 11),Fengchi (GB 20),Hegu (LI 4),Taixi (KI 3),Taichong (LR 3),and Yanglingquan (GB 34) were taken for body acupuncture.The scalp acupuncture needles are connected to the electroacupuncture instrument and a continuous wave is taken.The needles are retained for 20 minutes and three times a week.After three courses of treatment,the total effective rate in the scalp and body group was 82.05%,which was significantly higher than the control group (61.54%).Additionally,the UPDRS score also showed a significant improvement.Jiang Haiwei et al.[16] found that“Chansanzhen” combined with rehabilitation training and low-dose oral administration of benserazide and levodopa tablets can improve the motor and balance function of patients with early PD.The scalp acupuncture took the Four Shen Points (1.5 inches away from the front,back,left,and right sides of Baihui (DG 20) in the parietal region),and the body acupuncture took the Si Guan (bilateral Hegu (LI 4)and Taichong (LR 3)) and Fengchi (GB 20).Even reinforcing and reducing,the needles are retained for 30 minutes,once every other day,and 15 times during treatment.After two courses of treatment,the UPDRS III(movements examination and assessment)score and Berg balance scale score of the “Chansanzhen” group showed a significant improvement.In addition,Professor Qu Yanjin believes that the location of PD is the liver and brain,whereas the pathogenesis is an internal movement of the liver wind and wind phlegm stasis that obstruct brain collaterals.During the treatment,“Jiao's scalp” was selected to take the motor area and choreiform tremor control region,combined with body acupuncture to select acupoints by syndrome differentiation.After the first course of treatment,the patient's bilateral upper limbs tremors decreased with the lowered use of drugs.After four courses of treatment,the amplitude of tremor significantly decreased,the tremor time was shortened,and the drug was reduced to one-fourth of the original amount,which was sufficient in controlling symptoms.It exhibited significant clinical effects[17,18].

Other acupuncture therapies

Thick needle joined penetration is one of the effective methods for the treatment of PD.Penetration of the Shenzhu (DU 12)point can improve the UPDRS score of patients with PD [19].“Du Channel Thirteen Needles” and “Hands and Feet Twelve Needles”combined with burning acupuncture pricking the Du Channel and Ashi point (muscular fascia tension and tenderness point) show significant effects on patients with PD.After 8 and 12 weeks of treatment,various scores of UPDRS I,II,III,IV,and the 39-item Parkinson's disease questionnaire showed a significant reduction [20].Floating acupuncture of PD is associated with limb pain.It significantly reduces the McGill Pain Questionnaire Short Form score and the 39-item Parkinson's disease questionnaire score,effectively relieves pain symptoms,and improves the patients' quality of life [21].Scholars have also found that electroacupuncture combined with body acupuncture can effectively improve the UPDRS score and muscle tension assessment scale score of patients with PD.It has a significant effect on muscle stiffness.Therefore,there is a better effect of connecting 100 Hz electroacupuncture[22].

Study on the mechanism of acupuncture therapy for PD

Regulating dopaminergic neuron secretion in substantia nigra

The onset of PD is closely related to the damage of dopaminergic neurons.During the onset,the dopaminergic neurons in the midbrain substantia nigra are severely damaged.As a result,PD shows characteristic damage specific to dopaminergic neurons in the substantia nigra [23].Dopamine is synthesized with tyrosine as a substrate,which is hydroxylated by mesencephalon substantia nigra tyrosine hydroxylase(TH)and decarboxylated by dopa decarboxylase.Studies have found that acupuncture can improve the ethology and pathology of mice with PD.Its mechanism of action may be realizing the above process by increasing TH expression in the substantia nigra and reducing the loss of dopaminergic neurons in mice.Wang Qiang et al.[24] found that“Xiusanzhen”can effectively alleviate the pathological changes of olfactory bulbs in PD model mice and significantly increase TH expression in the substantia nigra.Bai Yan et al.[25]found an increased expression of cysteine protease-3 (caspase-3) and apoptosis of dopaminergic neurons in the nigra of rats with PD,and electroacupuncture at Baihui (DU 20) and Temple(EX-HN5) acupoints can lead to a decreased expression of caspase-3 in nigra and inhibit the apoptosis of dopaminergic neurons.

Improvement of oxidative stress

Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) are essential enzymes that catalyze the decomposition of hydrogen peroxide in the body.Glutathione (GSH) can fight against oxygen-free radical peroxidation and inhibit the corresponding apoptosis and necrosis.SOD can eliminate oxygen-free radicals through disproportionation.As one of the lipid peroxides,malondialdehyde can reflect the degree of lipid peroxides in the body[26].It has been discovered that the function of the antioxidant system in PD model rats was decreased,whereas SOD,GSH-Px activity,and GSH content decreased.

Electroacupuncture can improve the antioxidant capacity of PD model rats and reduce the damage of oxygen-free radicals on brain tissue.Guo Chunxia et al.[27] confirmed that electroacupuncture can considerably increase GSH content,improve SOD and GSH-Px activity,and reduce malondialdehyde content in PD model rats.Shi Bo [28] found that the combination of low-dose zinc and electroacupuncture could regulate the level of anti-oxidative stress in the body and have a preventive and therapeutic effect on rats with PD.

Inhibition of inflammatory response

During the PD pathological process,neuronal degeneration and necrosis and inflammatory response are related to microglial activation,the pathological characteristics of which are abnormal aggregation and phosphorylation of α-synuclein in the specific regions of the central nervous system.α-synuclein can activate microglial cells,the excessive activation of which can produce a large amount of tumor necrosis factor-α(TNF-α),interleukin-1β (IL-1β),and interferon-γ(IFN-γ) [29].“Xiusanzhen” can reduce the degeneration of dopaminergic neurons by inhibiting the expression of TNF-α and IL-6 in the olfactory bulb and substantia nigra of mice [30].Wang Shuju et al.[31] found that electroacupuncture can regulate the MAPK/JNK signaling pathway in PD model rats,decrease the expression of p-c-Jun in the substantia nigra,and reduce the expression of inflammatory factors TNF-α,IFN-γ,and IL-1β.

Anti-excitotoxicity

Excitatory amino acids,including glutamic acid (Glu)and aspartic acid,can cause toxic effects on neurons when they are released excessively or the inactivation mechanism is damaged.Physiologically,the activities of striatum neurons are accomplished by the mutual restriction between the inhibition of dopaminergic neurons in the substantia nigra and the excitation of Glu-energic neurons in the cerebral cortex.When dopaminergic neurons in the nigrostriatal striatum are absent,the excitatory activity of Glu-energic neurons can be increased as a result,followed by an increase in the excitatory amino acids content,further aggravating the degeneration and even death of striatum neurons[32].Wang Shuju et al.[33,34] found that the protective effects of electroacupuncture on dopaminergic neurons in PD rats may be related with the following:the electroacupuncture can increase the expression and activity of glutamate transporter in the brain and reduce the cytotoxicity caused by extracellular Glu.

Regulating mitochondrial dysfunction

During the onset of PD,the decrease of mitochondrial complex activity in brain tissue will reduce the synthesis of ATP,thereby leading to the inability of membrane potentials to maintain balance,which in turn will cause electrons to leak from the respiratory chain,increase the production of reactive oxygen species,and cause the degeneration of dopaminergic neurons.In dopaminergic neurons,in case that the damaged mitochondria do not break down in time,the resulting neurotoxicity can even cause dopaminergic neurons death,eventually triggering PD [35].Sun Hongmei et al.[36] found that acupuncture at Baihui(DU 20) and Dazhui (DU 14) acupoints can improve behavioral disorders in mice with PD,reduce the loss of dopaminergic neurons in the mesencephalic substantia nigra,reduce mitochondrial structural damage,and increase the activity of mitochondrial complex II.To some extent,it alleviates the disorders in mitochondrial ATP production and improves the mitochondrial function.Liu De et al.[37] found that electroacupuncture can delay apoptosis via increasing the mitochondrial transmembrane potential of neurons in PD model rats.

Summary and prospect

To summarize,clinical medicine is often combined with acupuncture therapy such as scalp acupuncture,eye acupuncture,abdominal acupuncture,and body acupuncture in PD clinical treatment,which has shown a preferable clinical effect.The therapeutic mechanism of acupuncture for PD involves multiple targets,such as regulating dopaminergic neuron secretion in the substantia nigra,improving oxidative stress,inhibiting inflammatory response,anti-excitatory toxicity,and regulating mitochondrial dysfunction.However,acupuncture therapy for PD still lacks unified and standardized treatment algorithms,adequate cases of long-term efficacy observation,and high-quality evidence-based medicine research works.In the future,we will strengthen the clinical standardization study of acupuncture therapy for PD,summarize the advantages and disadvantages of various acupuncture treatments,formulate standardized clinical treatment programs,and study the related mechanisms of acupuncture treatment of PD in details,so as to provide theoretical guidance during the clinical rehabilitation and treatment for acupuncture in patients with PD.