Modern acupuncture-like stimulation methods: a literature review Academic research paper on "Medical engineering"

integr med res 4 (2015) 195-219

Available online at www.sciencedirect.com

Integrative Medicine Research

journal homepage www.imr-journal.org

Review Article

Modern acupuncture-like stimulation methods: a literature review

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Min-Ho Jun, Young-Min Kim,Jaeuk U. Kim *

KM Fundamental Research Division, Korea Institute of Oriental Medicine, Daejeon, Korea

article info

Article history: Received 12 August 2015 Received in revised form 23 September 2015 Accepted 24 September 2015

Keywords:

acupuncture-like stimulation

devices electrical stimulation laser stimulation magnetic stimulation ultrasonic stimulation

abstract

Acupuncture therapy has been proved to be effective for diverse diseases, symptoms, and conditions in numerous clinical trials. The growing popularity of acupuncture therapy has triggered the development of modern acupuncture-like stimulation devices (ASDs), which are equivalent or superior to manual acupuncture with respect to safety, decreased risk of infection, and facilitation of clinical trials. Here, we aim to summarize the research on modern ASDs, with a focus on featured devices undergoing active research and their effectiveness and target symptoms, along with annual publication rates. We searched the popular electronic databases Medline, PubMed, the Cochrane Library, and Web of Science, and analyzed English-language studies on humans. Thereby, a total of 728 studies were identified, of which 195 studies met our inclusion criteria. Electrical stimulators were found to be the earliest and most widely studied devices (133 articles), followed by laser (44 articles), magnetic (16 articles), and ultrasound (2 articles) stimulators. A total of 114 studies used randomized controlled trials, and 109 studies reported therapeutic benefits. The majority of the studies (32%) focused on analgesia and pain-relief effects, followed by effects on brain activity (16%). All types of the reviewed ASDs were associated with increasing annual publication trends; specifically, the annual growth in publications regarding noninvasive stimulation methods was more rapid than that regarding invasive methods. Based on this observation, we anticipate that the noninvasive or minimally invasive ASDs will become more popular in acupuncture therapy.

© 2015 Korea Institute of Oriental Medicine. Published by Elsevier. All rights reserved.

1. Introduction

Stimulation of acupoints and meridians has been an important therapeutic modality in traditional Eastern medicine, and it has also become popular in the West, as its clinical effectiveness has been demonstrated through extensive research.

Acupuncture and related modern technologies are increasing in popularity worldwide. According to a 2002 World Health Organization report, acupuncture treatment was shown to be effective in controlled trials of 29 diseases, symptoms, or conditions.1 However, the safety of acupuncture has engendered controversy with respect to infection, inflammation, and pain management.

* Corresponding author. KM Fundamental Research Division, Korea Institute of Oriental Medicine, 1672 Yuseongdaero, Yuseong-Gu, Deajeon 305-811, Korea.

E-mail address jaeukkim@kiom.re.kr (J.U. Kim). http://dx.doi.org/10.1016/j.imr.2015.09.005

2213-4220/© 2015 Korea Institute of Oriental Medicine. Published by Elsevier. All rights reserved.

Clinical effectiveness of acupuncture has widely been studied during the past four decades.2-6 In addition to the demonstrated effectiveness of traditional acupuncture practices, increased demand has arisen for the development of modern acupuncture-like stimulation devices (ASDs), which are simpler to quantify and standardize and are less dependent on the manipulation techniques of individual clinicians.

The first modern ASD dates back to the early 1950s, which was based on electrical stimulation (ES).7,8 In addition to its long history, ES is the most extensively studied ASD.9 Recently, however, several types of ASDs have extensively been studied for their clinical effectiveness and noninferiority to manual acupuncture, including laser stimulation (LS)10 and magnetic stimulation (MS).11 In this review, we summarize recent studies of popular ASDs. We first describe the most popular types of ASDs, discuss their clinical effectiveness and target symptoms, and finally, discuss the annual research trends regarding popular ASDs.

2. Methods

To analyze the popularity and features of methods for stimulation of acupoints, we searched for studies in the Medline, PubMed, Cochrane Library, and Web of Science electronic databases from their inception to June 2014. First, we searched for studies related to acupuncture or acupoint stimulation, which yielded > 22,000 studies, of which approximately 20,000 were redundant. Among the latter studies, approximately 3000 were related to moxibustion, 1600 to massage (or acupressure), 200 to the cupping method, 5400 to ES, 900 to LS, 700 to MS, and 300 to ultrasound stimulation (US). To narrow the search scope to ASDs, we refined the search to [(acupoint* or "acupuncture point*" or meridian*) and (stimul* or irritat* or excit* or response or respon* or react* or reflex or measur* or diagnos*) and (electric* electro* or magnet* or infrared or IR or laser or ultraviolet or UV or ultraso*) not (rat or monkey or dog or pig or cat or mouse or mice or rabbit or rodent*)]. We excluded laboratory experiments on animals, studies that were not written in English, and reviews. We searched 728 articles obtained from the electronic databases, excluding 489 articles that included studies on animals, manual

acupuncture-only clinical trials, non-English-language articles, and review articles by screening the titles and abstracts. A total of 44 studies were excluded from the selected 239 articles because of duplication. Finally, 195 studies met the inclusion criteria and were evaluated in detail. The topics of these 195 articles were ES (133), LS (44), MS (16), and US (2), as shown in Fig. 1. Prior to describing the results of the detailed analysis, we introduce the features and research history of ES, LS, MS, and US in the following sections.

2.1. Electrical stimulation

Low electrical impedance and high conductance are recognized as typical electrical properties of acupoints and meridians.12-14 In the Western hemisphere, the electrical properties of acupoints and meridians have been investigated since the 1950s. In 1958, Niboyet and Mery15 reported the points with low skin impedance using the Wheatstone bridge, whereas in 1962, Kramar16 showed that acupoints have high capacitance compared with neighboring points. Voll7 devised an ES device to apply to acupoints and meridians, thereby establishing a method that was called "electroacupuncture according to Voll." This method of Voll7 greatly stimulated clinical and research activities associated with ES at acu-points and meridians. In the East in 1956, Nakatani8 reported that electrical pathways connected the points with low skin resistance and named them "Ryodoraku." Today, ES can be classified into five types: electroacupuncture (EA), tran-scutaneous electrical acupoint stimulation (TEAS), auricular electroacupuncture (AEA), transcutaneous electrical nerve stimulation (TENS), and electrical heat acupuncture (EHA). EA is an electrical, minimally invasive stimulation technique applied to acupoints. TEAS is an electrical, noninvasive stimulation technique applied to acupoints. AEA is a subtype of EA applied to acupoints of the ear. TENS is an electrical, nonin-vasive stimulation technique applied to the nervous system (nonacupoints). EHA is similar to EA with the exception that a needle heated by an electric current is used at acupoints. Of the 133 articles on ES, 54 pertained to EA, 69 to TEAS, six to AEA, three to TENS, and one to EHA. To simplify the discussion, we categorized ES into EAs and TEASs, where EAs represented

Fig. 1 - Flow diagram of literature survey.

all invasive techniques, such as EA, AEA, and EHA, and TEASs included all noninvasive techniques, such as TEAS, auricular TEAS, and TENS.

2.2. Laser stimulation

Studied since the 1970s, LS is used to expose acupoints of the human body to low-energy laser beams. A review article17 noted that studies using LS were conducted between 1970 and 1972 in the USSR. Nevertheless, Friedrich Plog's18 study published in 1976 is well known as the first report of implementation of LS at acupoints. Since the 1980s, LS has been recognized as an effective method for stimulating acupoints without needles. Applications of LS at acupoints were mostly described as noninvasive in the studies reviewed, with only a few being described as invasive. Here, we do not distinguish invasive techniques from noninvasive stimulation.

2.3. Magnetic and ultrasonic stimulation

MS is used to access the body's magnetic fields by stimulating acupoints, and MS of acupoints has been studied since the 1970s. Transcranial magnetic stimulation is one of the most frequently used MSs and was introduced by Barker19 in 1985. In 1980, Inoue20 applied for a patent for a device used for MS of body acupoints, and in 1982, Katayama21 reported

the meridian magnetic analgesia of acupuncture stimulation (published in Japanese). The MS used in all 16 papers consisted of noninvasive stimulations at acupoints.

US is used to irritate acupoints using a narrow, cylindrical, high-frequency beam of sound. Characteristics of phonation and sound transmission in meridians were reported in the 1980s, and a study on US of acupoints was published by Jin22 in 1984. Only two studies that we identified in the electronic databases were relevant.

3. Results

The aforementioned four types of ASDs were classified into the following 13 categories according to the stimulation purposes: (a) analgesic effect; (b) pain relief; (c) physiological change; (d) improvement of the alimentary system; (e) prevention of nausea and vomiting; (f) recovery of muscle fatigue or improvement of muscle strength; (g) reduction of body weight; (h) treatment of depression; (i) treatment of addiction, such as addiction to tobacco, narcotics, and alcohol; (j) treatment of stroke; (k) treatment of various diseases; (l) characteristics of stimulation; and (m) brain activity. Fig. 2 shows how the four types of ASDs were distributed between the 13 categories for research purposes. It also shows the ratio of randomized controlled trials (RCTs) to efficacies for the 13 categories. The numbers shown in the uppermost boxes

ES (133) (a) (b) (c) (d) (e) (f) 19 33(3)17(1) 10 11 5(2) LS (44) (a) (b) (c) (d) (e) (f) 2 8 11 0 1 0(1) MS (16) (a) (b) (c) (d) (e) (i) 0 0 3 0 0 2 US (2) (a) (b) (c) (d) (e) (f) 0 110 0 0

(g) (h) © © (k) © (m) 5(1) 0 3 4 10 4 12 (g) (h) © © (k) © (m) 0 2 2 0 5 4 9 (g) (h) © © (k) © (m) 0 0 0 0 1 0 10 (g) (h) © © (k) © (m) 0 0 0 0 0 0 0

Fig. 2 - Distribution of the four ASDs with respect to the 13 research categories from (a) to (m) whereby the numbers of RCTs and the therapeutic effectiveness are shown for each category. Numbers reflect the article counts, with the numbers in parentheses for the four types indicating the number of cases of overlap between the stimulations, and the numbers in parentheses below the efficacy (%) are presented when the efficacy was unclear. In RCT (%) = A/(A + B) % and (O:X = A:B), A is the number of RCTs and B is the number of non-RCTs. The same formula was applied to the efficacy percentages. When the efficacy was unclear, indicated by the numbers in parentheses, we considered those studies as not effective in computing the percent values. For example, % value = A/(A + B + b) for efficacy [O:X = A:B(b)].

ASD, acupuncture-like stimulation device; ES, electrical stimulation; LS, laser stimulation; MS, magnetic stimulation; RCT, randomized controlled trial; US, ultrasound stimulation. O = yes, X = no. Example: RCT (O:X) = (RCT:non-RCT), Efficacy (O:X) = (efficacious:not efficacious).

Table 1 - Summary of studies on analgesic effects with the four ASDs

Reference Stimulation Stimulation Symptom Control Effect

type site

Jiang et al23 TEAS LI4, PC8 Healthy 46 individuals, TEAS/mock TEAS Analgesic effect

Wang et TEAS LI4, PC6, ST36 Sinusotomy 60 patients, random TEAS/control: no Analgesic effect

al24 stimulation

Zhang et TEAS T3 acupoints Ambulatory surgery 72 women, random TEAS/sham Recovery & decrease of

al25 anesthesia

Wu et al35 EA GV1, BL57 Hemorrhoids 120 cases, random EA (40)/sham EA Effects of preemptive

(40)/blank (40) analgesia

Lan et al26 TEAS Bi PC6, LI14, Total hip arthroplasty 68 elderly patients, random Reduction of postoperative

ipsilateral to surgery TEAS/sham TEAS analgesic requirement

surgery sire

ST36, GB31

Zheng et EA GV24, EX-HN3 Orotracheally 45 patients, random, no Sedation & analgesia

al36 intubated patients treatment/sham EA/EA

Cheing and TEAS/TENS Right elbow LI11, Healthy Randomized controlled trial, 45 Hypoalgesic effects

& Chan27 Nonacupoint individuals, random TEAS (15)/TENS (acupuncture points &

(right (15)/control-no stim (15) nerve points)

superficial

radial nerve)

DeSantana TENS Around the Unilateral inguinal Prospective, randomized, Hypoalgesic effect for

et al31 incision herniorrhaphy double-blinded, placebo-controlled postoperative pain

with epidural study, 40 patients, TENS

anesthetic (20)/placebo-TENS (20)

technique

Barlas et EA Bi LI10, Healthy (acupuncture Randomized, double-blinded, Hypoalgesic response

al37 HT5/ipsilateral naive) placebo-controlled study, 48

GB34, ST38 volunteers, control/placebo-EA no

stim/high-intensity

EA/low-intensity EA

Leung et EA Left SP1, LR1 Healthy 13 individuals, EA/before-EA/ after-EA Analgesic benefit

al40 (time sequence)

Litscher42 Acupressure/ EX-HN3 Healthy Randomized, controlled, blinded ECG similarities of

MA/LS crossover trial, 20 volunteers, acupressure-induced

acupress/MA/LA; APs/non-APs sedation & general

anesthesia (all)

Zhang et al EA Acupoints Healthy Eight8 individuals, EA/mock-EA Analgesic effect

Attele et 28 TEAS LI4, PC6 Healthy 22 individuals, TEAS/control Analgesic effect

al Chesterton TENS/TEAS GB34, radial nerve Healthy Randomized, double-blind, Hypoalgesic effect

et al29 or sham-controlled study, 240

extrasegmental participants, six6 TENS (180; 90 m,

90 f)/control (30; 15 m, 15 f)/sham

TENS (30; 15 m, 15 f); 4/110 Hz,

intensity, site

Yuan et al30 TEAS LI4, PC6 Healthy 20 individuals TEAS/morphine/TEAS + Analgesia effect

morphine/control

Morioka et EA ST36, GB34, BL60 Healthy 14 volunteers, EA/control No difference in minimum

al39 alveolar anesthetic

concentration

Lin et al41 EA Bi ST36 Lower abdominal Randomly, 100 women, control Reduction of postoperative

surgery (25)/sham-EA no stim (25)/LF-EA analgesic requirements &

2 Hz (25)/HF-EA 100 Hz (25) side effects (LF-EA,

HF-EA)

Greif et al32 ATEAS Auricular Healthy Randomized, double-blind, crossover Reduction of anesthetic

acupoints trial, 20 volunteers (10 m, 10 f), requirement

ATEAS/no treatment

Chen et al33 TEAS/TENS ST36/ Total abdominal Randomized controlled trial, 100 TENS was as effective as

dermatomal hysterectomy or women, sham-TEAS no stim TEAS, both were more

level myomectomy (25)/non-APs TEAS effective than stim at

procedures (25)/dermatomal-TENS (25)/TEAS non-APs

Table 1 - (Continued)

Reference Stimulation Stimulation Symptom Control Effect

type site

Wang et TEAS LI4 Healthy women Random, 101 participants, PCA Decrease in PCA opioid

al34 undergoing lower (26)/PCA + LP-TEAS (25)/PCA + requirement &

abdominal HP-TEAS (25)/PCA + sham-TEAS opioid-related side effects

procedures no stim (25) (HP-TEAS)

Brokhaus LS/MA Bi LI4, EX-UE Healthy Double-blind, 40 probationers, Analgesic effect of MA on

and& MA-LI4/LA-LI4, EX painful heat stim, no

Elger43 effect on pain (LA)

AP, acupuncture point; ASD, acupuncture-like stimulation device; ATEAS, auricular TEAS; EA, electroacupuncture; ECG, electrocardiogram;

HF, high frequency; HP-TEAS, high power TEAS; LA, laser acupuncture; LF, low frequency; LP-TEAS, low power TEAS; LS, laser stimulation;

MA, Manual acupuncture; PCA, patient-controlled analgesia; stim, stimulation; TEAS, transcutaneous electrical acupoint stimulation; TENS,

transcutaneous electrical nerve stimulation.

in Fig. 2 signify the numbers of articles. The numbers of overlapping articles are shown in parentheses under the 13 categories of the four ASDs, and the numbers in parentheses below the efficacy (%) are presented when the efficacy was unclear.

To investigate the effectiveness of ASDs, we analyzed the efficacy of each stimulation type through the articles reporting effectiveness. The effectiveness of ES was stated in the fields of analgesic effect (94.7%), pain relief (90.9%), and reduction of nausea and vomiting (90.9%) based on the sample size of > 1000 trials. Based on the sample size of > 100 trials, ES was shown to be effective in improving the alimentary system (100%), improving muscle strength (100%), reducing body weight (100%), treating various addictions (60%), and treating stroke (100%), whereas LS was effective for pain relief (62.5%) and treating various addictions (100%). Based on a sample size of <100 trials, ES was shown to be a therapeutic possibility in various diseases such as orthostatic intolerance, autism spectrum disorders, supratentorial craniotomy, tinnitus, asthma, dyspnea, distress, and anxiety. LS presented potential in the treatment of nausea and vomiting, depression, menopausal symptoms, cholecystitis, renal failure, head injury, and interstitial cystitis. MS was a possible treatment for muscle and diving fatigue, whereas US demonstrated potential for relieving pain.

3.1. Analgesic effect

All the studies that reported an analgesic effect are shown in Table 1. Twelve articles reported an analgesic effect using TEASs,23-34 seven articles reported an analgesic effect using EAs,35-41 and two articles discussed LS.42'43 A total of 834 individuals received TEASs to enable estimation of the analgesic effect of their clinical application using RCTs, and all articles reported that the TEASs had an analgesic or hypoalgesic effect or decreased opioid requirements. A total of 348 individuals received EAs, and an effect of the EAs on analgesia, sedation, hypoalgesia, pre-emptive analgesia, and reduction of analgesic requirements was found in 334 patients. In 20 individuals who received acupressure, manual acupuncture (MA), and LS, a sedative effect was observed, and an anesthetic effect was observed in 60 individuals who received LS. Two of the 21 papers39,43 reported no significant analgesic effect of the EAs and LS.

3.2. Pain relief

As shown in Table 2, presenting the studies reporting the effect on pain relief, 15 articles reported using TEASs,44-58 EAs were used in 18 studies,59-76 other acupoint stimulations such as US were used in one study,77 and LS was used in eight studies.78-85 TEASs and EAs were compared in a total of 872 individuals to evaluate their effect on pain relief. Both had an effect on pain relief in two studies; however, the effect of EAs was reported to be superior to that of TEASs in one study. Of 1046 individuals who received TEASs, 926 experienced relief or a reduction in various types of pain. Of the 877 individuals who received EAs, 628 also experienced pain relief. Of the 435 individuals who received LS, 230 experienced relief of dysmenorrhea pain or carpal tunnel syndrome pain, whereas 50 individuals who received US experienced an effect on short-term segmental antinociception. Six of the 42 papers44,47,64,79,82,84 reported no statistically significant effect on pain relief when TEASs, LS, EAs, LS combined with paracetamol and chlormezanone, and LS were applied to the acupoints of study participants.

3.3. Treatments of the alimentary system

As summarized in Table 3, ES (TEASs and EAs) was the primary ASD method for treating digestive disorders. Of these studies, seven that investigated TEAS86-92 and three that evaluated EA93-95 comprise this category. In total, 149 individuals who received TEAS experienced a beneficial effect on the alimentary system, as did 68 individuals who received EA. No study reported statistically insignificant results regarding stimulation of the alimentary system.

3.4. Prevention of nausea and vomiting

All the studies shown in Table 4 employed ASDs for the prevention of nausea and vomiting. ES was primarily applied for the prevention or treatment of nausea and vomiting, except for one study that used LS for this purpose. TEAS was the main method used for preventing nausea and vomiting: we retrieved nine articles on TEAS,96-104 two on EA,105,106 and one on LS.107 A total of 830 individuals who received TEAS experienced an effect on prevention, reduction, or treatment of postoperative nausea and vomiting and nausea or vomiting. A total of 224 individuals who received EA

Table 2 - Summary of studies on pain relief with the four ASDs

Reference Stimulation Stimulation Symptom Control Effect

type site

Mucuk & Baser 44 TEAS LI4, SP6 Pregnant women Bi LI4-TEAS (40)/SP6-TEAS Labor pain relief, not

(40)/control (40) no stim statistically significant

Sun et al45 TEAS PC6 Driver fatigue - Able to withstand driver

fatigue

Vassal et al46 TENS Left common Healthy 20 individuals, TENS/sham Pain relief

peroneal nerve TENS (left thigh)

Kim et al59 EA Bi LI4, TE3, GV39, CIPN Randomized, Treatment for CIPN,

GV41, SP6, LR3, patient-assessor-blinded, trials

Ba Feng, Ba Xie controlled trial, 40 patients,

EA (20)/sham EA (20)

Lee et al60 EA Bi ST36, GB39, PDN 3-armed, randomized, Treatment for PDN, trials

SP9, PC6, LR3, controlled pilot trial, EA

GB41 (15)/sham EA (15)/usual care

Mucuk et al47 TEAS Bilateral LI4 Labor pain Random TEAS/control no TEAS; Pain relief, not

all standard treatments statistically significant

Ni et al48 TEAS Bilateral PC6 Children with 70 eligible children, random, Attenuation of

congenital heart TEAS (34)/control-no stim myocardial injury in

defects (36) children undergoing

cardiac surgery

Wu et al49 TEAS LI4, SP6 Gynecology Randomized controlled trial, 66 Mitigation of pain in

patients patients (f), TEAS (34)/control dysmenorrhea

(primary non-APs (32)

dysmenorrhea)

Yoshimizu et al72 EA/TEAS For acupoints in Shoulder & neck Randomized crossover trial, 90 Reduction in pain (EA >

trapezius pain patients, EA/TENS TEAS)

muscle

Musial et al73 EA LI4, LI10 Healthy Double-blind design, 125 Reduction of

individuals, EA (25)/tramadol experimentally

(25)/ibuprofen (25)/placebo induced ischemic pain

pill (25)/no treatment (25)

Choi et al61 EA/meditation LI4, LI10 Vipassana Semirandomized trial, Reduction in the pain

meditators meditators(8)/nonmeditators induced by SETT

(20)-EA/nonmeditators (20)-no EA

Yeh et al50 TEAS BL40, GB34, HT7, Spinal surgery Placebo- & sham-controlled Reduction in

PC6 receiving study, random TEAS postoperative pain,

patients (30)/TEAS-sham point (30)/no analgesic usage

TEAS (30)

Montenegro et al51 TEAS TE5, CV6 Healthy 32 volunteers, random Increase in the latency of

TEAS/sham TEAS pain threshold

Yeh et al53 TEAS Acupoints Lumbar spinal Randomized controlled Improvement of acute

surgery repeated measures design, postoperative pain

99 patients, ES/sham-AP management without

ES/no ES adversely affecting

vital signs

Takamjani et al81 LS Acupoints Wrist pain Randomized controlled trial, 70 Increase in mean value

women, LS (33)/control (37) no LS of pain threshold

Lee & Lee62 EA Bi BL32, BL33, Chronic prostati- 39 men, random 3 group Pain relief effect

GB30 tis/chronic exercise + EA/exercise +

pelvic pain sham EA/exercise

syndrome

Kempf et al78 LS Bi SP6, LR3, LI4; Minimum Randomized controlled double Dysmenorrhea

right CV3, ST36 menstrual pain blind pilot trial, 48 women, treatment

LA (18)/placebo-LA (30)

Glazov et al82 LS Acupoints Chronic Double blind, 2-group parallel Not showing a specific

nonspecific randomized controlled trial, effect for chronic

low-back pain 100 participants, low-back pain

LA/sham-LA

Table 2 - (Continued)

Reference Stimulation Stimulation Symptom Control Effect

type site

Chan et al74 EA Acupoints on the Chronic neck pain Single-blind, randomized, Significant

wrist sham-controlled trial, 49 improvements of

patients, EA (22)/sham-EA chronic neck pain

Jubb et al63 EA Acupoints Osteoarthritic knee Blinded randomized trial, MA Symptomatic

pain & disability (34)/EA (34)/sham MA (34) improvement

Srbely et al77 US Right Identifiable myofascial Randomized controlled study, Short-term segmental

supraspinatus trigger points 50 individuals, random antinociceptive

trigger point US/sham US (off) effects on TPs

Ye et al54 TEAS + PCA LI4, PC8; Jiaogan, Craniotomy & required Randomized control, 40 Enhancement of the

Shenmen, pain relief following patients, PCA + TEAS effect of pain relief &

Shen, Waifei, surgery (20)/PCA (20) reduction of adverse

Naogan, reactions

Pizhixia (ear

acupoints)

Michalek-Sauberer AEA Auricular Molar tooth extraction Prospective, randomized, No reduction in either

et al64 shenmen, double-blind, pain intensity or

mouth, tooth placebo-controlled study, analgesic

149 patients, AEA (76)/AMA consumption in a

(37)/sham AEA no stim no molar tooth

needle (36) extraction model

Zhang et al65 EA GB34, GB39 Healthy (right 12 volunteers, Pain relief

handiness) EA/sham-points

EA/shallow EA

subcutaneous needling

Yip et al55 TEAS + EMMW - Subacute neck or Randomly, 47 individuals, Reduction in pain

low-back pain TEAS + EMMW (23)/control intensity, stress, &

(24) stiffness level

Fang et al52 TEAS/EA Acupoints Periarthritis of 360 cases, TEAS (186)/EA (174) Therapy for periarthritis

shoulder at different of shoulder, no

stages significant differences

(TEAS/EA)

Aigner et al79 LS + paracetamol, 22 acupuncture Whiplash injuries Prospective, randomized Ineffective in

chlormezanone points placebo-controlled trial, LA management of

(23)/placebo-LA (22) whiplash injuries

Sator- AEA Auricular 29, 55, In vitro fertilization 94 women, random, AEA Reduction of pain

Katzenschlager 57 (32)/AMA (32)/pharm. (30) intensity

et al66

Wong et al75 EA LI4, GB34, GB36, Operable non-small Random, 25 patients, EA Management of

TE8 cell lung carcinoma (13)/sham-EA (12) post-thoracotomy

patients who wound pain

received

thoracotomy

Weng et al56 TEAS LI10, LI11 Tennis elbow pain for Randomly, 20 patients, 5 kHz Effective in the

at least 3 mo modulated LF-TEAS 2 Hz treatment of patients

(20)/5 kHz modulated with tennis elbow

HF-TEAS 100Hz pain (LF-TEAS,

(20)/sham-TEAS, different HF-TEAS)

time slots

Tsui & Cheing67 EA/EHA 6 acupuncture Chronic low-back pain 42 individuals, random Treatment of chronic

points EA/EHA/control; all low-back pain

exercise

Sator- AEA Auricular Chronic low-back pain Prospective, randomized, Treatment of chronic

Katzenschlager acupuncture double-blind, controlled low-back pain

et al68 points 29, 40, study, 61 patients, random

55 AEA (31)/sham-AEA no

stim (30)

Sator- AEA Cervical spine, Chronic cervical pain Prospective, randomized, Treatment of chronic

Katzenschlager shenmen, patients without double-blinded, controlled cervical pain

et al69 cushion radicular symptoms study, 21 patients, EA

with insufficient (10)/control (11)

pain relief

Table 2 - (Continued)

Reference Stimulation Stimulation Symptom Control Effect

type site

Ng et al70 EA/TEAS ST35/EX-LE4 OA-induced knee Single-blinded randomized Reduction of

pain controlled trial, 24 OA-induced knee pain

individuals (1 m, 23 f), EA

(8)/TEAS (8)/control standard

therapy (8)

Naeser et al80 LS/TENS Shallow CTS Randomized, double-blind, Treating CTS pain

acupuncture placebo-controlled, crossover

points/wrist trial, 11 cases, red LS/IR

LS/TEAS/sham (off)

Tsui & Leung 71 EA GB34, ST38 Chronic tennis Single-blinded randomized Treating patients with

elbow controlled trial, 20 patients, tennis elbow

Zoghi & ATEAS/ATENS 4 auricular Healthy Double-blind within-subject Increase in

Jaberzadeh57 acupoints design, randomly, 90 experimental pain

individuals, HV-ES threshold (HV-ES,

(30)/HV-sham-ES non-APs sham)

(30)/no ES (30)

Lorenazana58 TEAS HT7, LI4 Episiotomy pain Randomized, double-blind, Relief of episiotomy

controlled trial, 68 patients, pain (TEAS >

TEAS (38)/control (30) lidocaine)

King et al83 ALS Auricular Healthy 80 individuals, ALS (41)/control Increase in mean pain

acupoints (39) sham-ALS threshold after

treatment

Waylonis et al84 LS Acupoints Myofascial pain Crossover double-blind trials, No statistical difference

syndromes 62 patients, LS/placebo between the

(fibrositis, treatment and

fibromyalgia) placebo groups

Kreczi & Klingler85 LS Acupoints Radicular and Prospective randomized Mean pain levels (lower)

pseudoradicular single-blind crossover study,

pain syndromes 21 patients, LS/mock LS

Ernst & Lee76 EA LI4 Normal individuals Crossover repeated-measure Pain threshold increase

design, 5 individuals,

control/EA/EA + naloxone/EA

+ placebo

AEA, auricular electroacupuncture; ALS, auricular laser stimulation; AMA, auricular manual acupuncture; AP, acupuncture point; ASD,

acupuncture-like stimulation device; ATEAS, auricular TEAS; ATENS, auricular TENS; CIPN, chemotherapy-induced peripheral neuropathy; CTS,

carpal tunnel syndrome; EA, electroacupuncture; EHA, electrical heat acupuncture; EMMW, electromagnetic millimeter wave; ES, electrical

stimulation; f, female ; m, male; HF, high frequency; HV, high voltage; IR, infrared; LA, laser acupuncture; LF, low frequency; LS, laser stimulation;

MA, manual acupuncture; OA, osteoarthritis; PCA, patient-controlled analgesia; PDN, painful diabetic neuropathy; pharm, pharmacological

treatment; SETT, submaximum effort tourniquet technique; stim, stimulation; TEAS, transcutaneous electrical acupoint stimulation; TENS,

transcutaneous electrical nerve stimulation; TP, trigger point; US, ultrasound stimulation.

also experienced either the same effect or controlled emesis, whereas 40 individuals who received LS experienced a decrease in the incidence of vomiting. We observed that TEAS has been steadily applied in the prevention of nausea and vomiting, and exceeded EA in the number of clinical studies since 2003. This finding implies that the effectiveness of TEAS in preventing nausea and vomiting has been confirmed, and that TEAS was preferred to EA because of the infection risk and pain due to the use of needles with EA.

3.5. Improvement of the muscle system

Studies regarding ASDs that were related to the recovery of muscle fatigue or improvement of muscle strength are shown in Table 5. MS and ES were used to reduce muscle fatigue or improve muscle strength. This category included two studies on MS108'109 and five studies110-114 on ES. The two MS studies,

which were conducted by the same research group, reported the effective recovery of muscle fatigue. One study109 reported better performance of MS than TEAS with respect to the therapeutic effect on muscle fatigue, and we expect more studies to validate this report.

3.6. Reduction in body weight

All the papers investigating the reduction in body weight were associated with ES, as shown in Table 6. EAs115,118,119 and TEASs116,117 were applied to facilitate the reduction in body weight. One study117 stated that TEAS was as effective as EA in weight reduction. A total of 193 individuals who received ES experienced a reduction in body weight or fat, and an improvement in body mass index or body composition. All the studies reporting on the reduction in body weight claimed significant effects. More studies are required to substantiate the effectiveness of ES for body weight reduction.

Table 3 - Summary of studies on the effects of the four ASDs on alimentary system

Reference Stimulation Stimulation Symptom Control Effect

type site

McNearney et a il86 TEAS PC6, ST36 SSc 17 patients, all TEAS Enhancement of gastric

myoelectrical functioning in SSc

Leung et al87 TEAS LI4, PC6, ST36 Healthy 40 individuals, random Reduction of rectal discomfort

TEAS/placebo TEAS

Chen et al93 EA ST36, ST37, ST25, Female constipation Single-blind, randomized trial, Improvement of constipation

ST28, CV4, CV6 30 females, EA (14)/sham EA

Liu et al88 TEAS PC6, ST36 Functional Double-blind, crossover study, Improvement of dyspepsia

dyspepsia 27 patients, random symptoms

acute-TEAS/chronic (2w)

Wang et al94 EA ST36, LI4 Type 2 diabetes Single-blind, randomized pilot Reduction of the dyspeptic

(symptoms of study, 19 patients, EA symptoms of diabetic

gastroparesis) (9)/sham EA (10) gastroparesis

Sallam et al89 TEAS Gastrointestinal (GI) SSc 17 patients, TEAS/baseline Treatment of upper GI

acupoints symptoms

Xu et al95 EA ST36, PC6 Functional 19 patients, acute-EA Relief of dyspeptic symptoms

dyspepsia (10)/short-term (2w) EA (9)

Zou et al92 TEAS PC6 Healthy Random, 26 volunteers, Inhibition of frequency of

TEAS/sham transient lower esophageal

APs-TEAS/naloxone sphincter relaxations

Xing et al90 TEAS ST36, PC6 Diarrhea- 7 patients, Reduction of rectal sensitivity

predominant ttd c: TEAS/sham-TEAS/control in IBS patients

Chang et al91 TEAS ST36 IBS Healthy (males) 15 volunteers (males) EA/TEAS Enhancement of gastric

myoelectrical regularity,

bradygastria not significant

AP, acupuncture point; EA, electroacupuncture; GI, gastrointestinal; IBS, irritable bowel syndrome; SSc, scleroderma; TEAS, transcutaneous

electrical acupoint stimulation.

3.7. Treatment of depression, addiction, and stroke

Two studies investigating the treatment of depression using LS,120,121 five studies evaluating the treatment of various addictions (i.e., alcoholism and addictions to tobacco and narcotics) using ES122-124 and LS,125,126 and four studies examining the treatment of stroke using ES127-130 are shown in Tables 7-9, respectively. LS was used by a research group to treat depression120,121, whereas two studies used ES devices123,124, one used LS125 to treat tobacco dependence, one used an ES device in the treatment of drug abuse,122 and one used LS to treat alcoholism.126 Five studies showed that the use of ES and that of LS for treating various addictions were appropriate treatment adjuncts. ES was applied for treating stroke in four studies. All the studies in which stroke was treated, including treatment with a combination therapy consisting of TEAS and task-related training, reported treatment efficacy of TEAS or EA based on clinical trials involving 421 individuals. These results showed that ES is feasible for treating stroke. All the studies in these three categories claimed beneficial effects on the treatment of depression, various addictions, or stroke.

3.8. Physiological changes, diverse diseases, miscellaneous characteristics, and brain activities

All the papers regarding ASDs that induced physiological changes, treated various diseases, affected miscellaneous

characteristics, and induced brain activities are shown in Tables 10-13,131-174 respectively. Most studies in these categories were focused on phenomenological observations or consisted of a small number of clinical trials. Many more case studies are required to demonstrate the effects of ASDs on diverse diseases. These various investigations may expand the application of modern ASDs. Due to the limited scope of this review, we did not further investigate the diverse aspects of these studies.

4. Discussion

EAs, which are invasive types of ES, were the first and most intensively studied modern applications of ASDs. Recently, the number of publications regarding the clinical effectiveness of noninvasive stimulations, such as TEAS, LS, MS, and US, has been increasing (Fig. 3). The increase is more substantial for noninvasive acupuncture-like techniques, most likely due to the growing demands for painless acupuncture or acupoint stimulations. Among the 195 articles analyzed, the studies involving ES (EAs and TEASs) predominated (133 articles, 68%), followed by LS studies (44 articles, 23%). Studies involving MS (16 articles, 8%) or US (2 articles, 1%) were less common. The publication of ES studies has steadily increased since the early 2000s, whereas LS and MS showed similar increment patterns with delayed start-up points (i.e., the increases began in 2009 and 2011, respectively). Despite its long history, ES had a steady

Table 4 - Summary of studies on the effects of the four ASDs on nausea and vomiting

Reference Stimulation type Stimulation site Symptom Control Effect

Xu et al96 TEAS PC6 PONV Prospective, blind, & randomized study, 119 patients, TEAS/sham TEAS Prevention of PONV after infratentorial craniotomy

Wang et al97 TEAS Right PC6 Supratentorial craniotomy Random TEAS (40)/control-nonacupoint (40),all standard general anesthesia Prevalence of nausea, vomiting

Larson et al98 TEAS Acupuncture Patients undergoing Prospective, randomized, Postoperative nausea &

points cosmetic surgery blinded, clinical trial, 122 patients, random standard pharm./pharm. + EA vomiting

Liu et al99 TEAS Left-side PC6 Patients undergoing laparoscopic cholecystectomy 96 patients, random EA/placebo-EA no stim Reduction of nausea & vomiting, pain relief

Habib et al102 TEAS PC6/dorsum Cesarean delivery Random, 91 patients, TEAS No difference between

of wrist with spinal anesthesia (47)/sham-APs TEAS (44) the 2 groups (less PONV in 2 groups)

Kabalak et al100 TEAS PC6, CV13 Tonsillectomy under general anesthesia Randomized, controlled, prospective study, 90 children, TEAS (30)/pharm. dose (30)/no treatment (30) Prophylaxis of postoperative retching & vomiting in pediatric tonsillectomy

Kramer et al101 TEAS PC6 Patients receiving electroconvulsive therapy 11 patients, TEAS (9 good, 1 mixed, 1 no response) Treating nausea & vomiting

Rusy et al105 EA PC6 Tonsillectomy 120 patients, random EA (40)/sham-EA sham needle(40)/control no needle (40) PONV prevention

Zarate et al103 TEAS PC6 Laparoscopic cholecystectomy with standardized general anesthetic technique Sham-controlled, double-blinded study, random, 221 outpatients, TEAS/placebo no stim TEAS reduced postoperative nausea, but not vomiting

Shen et al106 EA Antiemetic High-risk breast 3-arm, parallel-group, Effective in controlling

acupoints cancer patients undergoing highly emetogenic chemotherapy regimen randomized controlled trial, LF-EA (37)/mock-EA (33)/no-EA (34) emesis (EA > pharm.)

Schlager et al107 LS Bi PC6 Postoperative vomiting in children undergoing strabismus surgery Double-blind, randomized, controlled study, 40 children, LS (20)/placebo (20) Incidence of vomiting significantly lower

McMillan & Dundee104 TEAS PC6 Cancer chemotherapy Antiemetic action, useful adjunct to both the older antiemetics & the new antagonist ondansetron

ASD, acupuncture-like stimulation device; EA, electroacupuncture; LF, low frequency; PONV, postoperative nausea and vomiting; pharm, Phar-

macological; stim, stimulation; TEAS, transcutaneous electrical acupoint stimulation.

but limited publication rate prior to 2000, whereas during the 1980s and 1990s, the number of publications on ES remained between zero article and two articles per year.

Fig. 4 shows the yearly publications of invasive (EAs) and noninvasive (TEASs) ES techniques. The total number of studies was similar between EAs (63 articles) and TEASs (70 articles). However, differences were observed in the number of publications per year; the publications associated with TEASs

showed a steady increase over time, which is in contrast to the stable annual publication pattern of EAs. Notably, the number of TEAS publications surpassed that of EAs in 2010. Specifically, TEASs were studied more than EAs over the past 5 years in the context of diseases with high therapeutic benefits, such as analgesic effect, pain relief, improvement of the alimentary system, and prevention of nausea and vomiting. The rising popularity of TEASs is presumably due

Table 5 - Summary of studies on the recovery of muscle fatigue or improvement of muscle strength with the four ASDs

Reference Stimulation type Stimulation site Symptom Control Effect

Kim et al108 MS LR9 Healthy 20 participants (males), Recovery of muscle fatigue

(males) MS (10)/no MS (10)

Kim et al109 TEAS/MS An acupoint Muscle TEAS/MS/no stim Therapeutic effect on muscle

fatigue fatigue (MS better)

Zhou et al110 EA ST36, ST39 Healthy randomized controlled Improvement of muscle

(males) trial, 43 young men, strength in both limbs

control/MA/

EA-APs/EA-non-APs

Ngai et al111 TEAS Bi LU7, EX-B1 Healthy 11 individuals (males), Higher postexercise FEV1,

(males) TEAS/placebo-TEAS prolongation of submaximal

no stim exercise

Huang et al112 EA ST36, ST39 Healthy 30 men, random Improvement of muscle

(males) EA/control strength of both limbs

Chiu et al113 TEAS + LS/exercise + LS/LS Acupoints Chronic neck Randomized clinical Improvement in disability,

pain trial, 218 patients, isometric neck muscle

TEAS + IR/Exercise + strength, pain (TEAS,

IR (LS)/IR (LS) exercise)

Milne et al114 TEAS/EA LI4, LI11 Healthy TEAS/EA Relief of muscle spasm &

musculoskeletal pain, &

restoration of mobility (TEAS)

AP, acupuncture point; ASD, acupuncture-like stimulation device; EA, electroacupuncture; FEV1, forced expiratory volume in 1 second; IR,

infrared; stim, stimulation; LS, laser stimulation; MA, manual acupuncture; MS, mag gnetic stimulation; TEAS, transcutaneous electrical acupoint

stimulation.

Table 6 - Summary of studies on the reduction in body weight with the four ASDs

Reference Stimulation Stimulation Symptom Control Effect

type site

Schukro et al115 AEA 18, 87, 91 at Obese females Prospective, randomized, Reduction of body weight

ear double-blinded study, 56 & BMI

patients (females), AEA

(28)/placebo dummy (28)

Chien et al116 TEAS ST36 Postmenopausal Prospective study, 49 women, Reduction in percentage

obese women random TEAS (24)/control body fat

no-TEAS (25)

Rerksuppaphol & TEAS/EA 10 acupoints Obese women Prospective randomized Effective method for

Rerksuppaphol117 open-label study, 45 women, weight reduction as

TEAS/EA seen with EA

Lin et al118 EA ST36, SP6 Postmenopausal Randomized controlled trial, 41 Improvement of body

women with women, EA (20)/control (21) composition

obesity

Jeong & Lee119 EA Acupoints Factitial panniculitis 2 cases (females), EA Weight reduction

AEA, auricular electroacupuncture; ASD, acupuncture-like stimulation device; EA, electroacupuncture; TEAS, transcutaneous electrical acupoint

stimulation.

Table 7 - Summary of studies on the treatment of depression with the four ASDs

Reference Stimulation type Stimulation site Symptom Control Effect

Quah-Smith et al120 Quah-Smith et al121 LS LS LR14, LR8, CV14, HT7 LR14, CV14, LR8, HT7, KI3 Depressed participants major depressive disorder Random block on-off design, 10 nondepressed participants, 10 depressed participants Randomized, double blinded, placebo controlled trial, 47 participants, LA/placebo LA Antidepressant effect Reduction of symptoms of depression

ASD, acupuncture-like stimulation device; LS, laser stimulation.

Table 8 - Summary of studies on the treatment of smoking and addiction of drug and alcohol with the four ASDs

Reference Stimulation Stimulation Symptom Control Effect

type site

Penetar et al122 TEAS PC6, TH5; LI4, Cocaine Single-blind, Modulation of mood &

PC8 dependent sham-controlled, anxiety, no significant

or cannabis crossover design, 20 reduction in drug use

dependent volunteers (11 m, 9 f) or drug cravings

TEAS/sham-

TEAS/baseline

Lambert et al123 TEAS LI4, PC8, PC6, Smoking 2 double-blind studies, 98 Antagonizing the urge

TE5 smokers, random to smoke in

TEAS-10 mA dependent smokers

(20)/TEAS-5 mA

(20)/placebo TEAS-0 mA

(16)/TEAS-5 mA (19);

intermittent 5 mA

Kerr et al125 LS 4 acupoints Smoking Double-blind, randomized Assisting in smoking

controlled trial, 387 cessation by reducing

volunteers, 3-LS 1-sham the physical

LS/4-LS/4-sham LS no symptoms of

stim withdrawal

Zalewska- ALS Neck; 10 Alcoholics 53 patients, He-Ne LS Adjunct treatment for

Kaszubska & auricular (neck) + argon ALS alcoholism

Obzejta126 acupoints

Georgiou et al124 TEAS SJ18, SJ17 Smoking Randomized controlled Insufficient power to

cessation trial, 216 smokers, detect real but small

TEAS/control TEAS no differences between

stim treatment conditions

ALS, auricular laser stimulation; ASD, acupuncture-like stimulation device; f, female; LS, laser stimulation; m, male; stim, stimulation; ST,

standard treatment; TEAS, transcutaneous electrical acupoint stimulation.

Table 9 - Summary of studies on the treatment of stroke with the four ASDs

Reference Stimulation type Stimulation site Symptom Control Effect

Ng & Hui-Chan127 TEAS + TRT ST36, LV3, GB34, Poststroke Case study, 1 man (age 61 Decreased impairment

UB60 y), TEAS + TRT & improved function

in an individual with

long-term chronic

stroke

Gong et al128 EA ST36 First-time cerebral Randomized, controlled, Effects on lower

infarction or clinical study, 240 extremity motor

hemorrhage, or a patients, EA (124)/control function in stroke

stroke history (116) patients

Kim et al129 TEAS Acupoints Ischemic stroke with 62 patients, 2 Hz-TEAS/120 Helpful for motor

motor dysfunction Hz-TEAS recovery after

ischemic stroke

(LF-TEAS)

Wong et al130 TEAS Acupoints Patients with Randomized, 118 patients, Convenient & effective

hemiplegia in comprehensive therapy for stroke

stroke rehabilitation + TEAS

(59)/comprehensive

rehabilitation (59)

ASD, acupuncture-like stimulation device; EA, electroacupuncture; LF, low frequency; TEAS, transcutaneous electrical acupoint stimulation; TRT, task-related training.

to the increasing needs for safety without needling, low infection risk, and relatively expedient utilization of clinical trials. The recent increase in studies of LS and MS, which are noninvasive, may be understood based on the same rationale.

According to a recent analysis, approximately 41% of clinical studies in acupuncture research from 1991 to 2009 addressed pain and analgesia.6 Among the studies evaluating the four types of ASDs published through 2014, the percentage

of clinical studies addressing pain and analgesia was 33%. This reduction in the percentage of studies focused on pain and analgesia is directly related to the recently heightened interest in acupuncture research on brain activities. The percentage of publications focused on brain activities that have been published since 2010 constitutes 61% (19 articles) of all such publications since 2001 (31 articles). Excluding the emerging category of brain activity, approximately 38%

Table 10 - Summary of studies on physiological changes with the four ASDs

Reference Stimulation type Stimulation site Symptom Control Effect

Cafaro et al131 LS Bi LI2, ST5, ST6, ST7, SI19, BL 13 Sjogren's syndrome 26 female, patients, LA/sham Salivary flow rate improvement

Kim et al175 MS LI4 Healthy Improvement of peripheral vascular system circulation

Li et al176 EA LI4, TE5, BL63, Supratentorial 29 patients, control (10)/EA Prevention of decrease of

LR3, ST36, craniotomy (9)/sham EA (10) immunoglobulin after

BL40, BL10, surgery, no significant

BL20, BL2, difference between EA &

EX-HN4 sham EA

Litscher et al132 LS GV20, PC6 Healthy Randomized crossover study, 11 volunteers (3 m, 8 f), MA (GV20;PC6)/red LA (GV20;PC6)/violet LA (GV20;PC6) HR & HRV control

Tsuruoka et al177 US LR3 Healthy 50 volunteers (40 m, 10 f), random US/MA Increase of blood flow volume

Wang et al133 LS Right LI4 Healthy 28 volunteers, random LA-LI4/LA-non LI4 Increase of left LI4 MBF, 40 min later after stimulation ceased, the MBF still increasing significantly

Raith et al134 LS LI4 Premature neonates 10 neonates (7 m, 3 f), initial temp/5 min stim temp/10 min stim temp Increase in the skin temperature

Lee et al178 MS PC9 Healthy 1 individual Parasympathetic activity of the autonomic nervous system

Jia et al179 EA Bi ST36, ST37 Healthy 20 volunteers, EA/sham EA Effect on autonomic function

Jones et al180 TEAS Bilateral PC6 Healthy 16 volunteers, random TEAS/sham-TEAS non-APs/no TEAS no-stim Change in artery

Lee et al181 EA LI4, LI11 Healthy Randomized crossover design, 14 participants, HF-EA 120 Hz/LF-EA 2 Hz Increase in autonomic nervous activity (HF-EA), enhancing sympathovagal balance (both)

Chang et al182 EA ST36, LI10 Healthy 15 volunteers, LF EA (low freq. 2 Hz)/HF EA (high freq. 100 Hz) Not affecting cardiovagal activity in normal volunteers

Cunha et al140 LS/MA 10 acupoints Circulatory deficiency 40 individuals, LS (20)/MA (20) Significant increase in systolic pressure of lower limbs, consequent improvement of the revascularization index

Litscher et al135 LS PC6 Healthy Randomized, controlled study, 13 volunteers, LS/control-laser off Decrease of HR

Kim et al183 EA PC5, PC6 Healthy EA (10)/sham-EA no stim (10) EEG, ECG, HR change

Lu et al184 MA, EA, TENS Bi ST36, ST37, palm, dorsum Healthy 20 volunteers, random sham-MA/MA/EA/TENS; before-A, during-A, after-A (time sequence) Cutaneous blood flow & temperature change

Zhang et al185 TEAS LI4, LI11 Normal & elevated blood pressure Randomly, 27 individuals, TEAS (13, 8 m, 5 f)/control (14, 9 m, 5 f) Reduction of systolic blood pressure, but not diastolic blood pressure

Zhang et al136 LS LI4, LI11 Healthy Randomized controlled pilot study, 45 students + faculty, LA/sham-LA laser off Reduction of blood pressure

Cakmak et al186 EA ST29, ST25 Healthy (m) Prospective, randomized study, 80 volunteers, MA/2 Hz-EA/10 Hz-EA Increase in testicular blood flow, helpful in clinical treatment of infertile men (ST29, 10 Hz)

Table 10 - (Continued)

Reference Stimulation Stimulation Symptom Control Effect

type site

Arai et al187 TEAS Bi PC5, Parturients Random, 36 singleton parturients, Reduction of the severity &

PC6/shoulder undergoing TEAS (12)/sham-APs TEAS incidence of hypotension after

cesarean (12)/no treatment (12) spinal anesthesia in

section under parturients

spinal

anesthesia

Cheung & Jones188 TEAS Bilateral PC6 Healthy (m) Single-blinded, randomized HR recovery after exercise

controlled trial, 28 individuals,

treadmill,

TEAS/pre-TEAS/placebo-TEAS

Banzer et al137 LS Right forearm Healthy Randomized, double-blinded, Improvement of blood flow

PC6 (nonsmoking placebo-controlled trial, 33

males) healthy (m), LA (18)/control no

laser (15)

Szeles & Litscher189 AEA Ear acupunc- Healthy (f) 2 healthy (f), AEA Modulation of blood flow

Litscher138 LS Acupuncture Healthy Randomized crossover study, 22 Changes in peripheral

points volunteers, LS microcirculation & surface

temperature of skin

Li et al190 MS (magni- GV14, PC6 Healthy (m) Randomly, 40 individuals, Modulating effect on

topuncture) MS/control MS non-APs sympathetic &

parasympathetic nerve

activities

Hsieh et al191 EA ST36 Healthy 8 volunteers, before/during /after Physiological mechanisms

EA responsible

Litscher & Schikora139 LS Vision- Healthy Randomized crossover trial, 27 Increases of blood flow in

related volunteers (13 m, 14 f), LA/MA ophthalmic artery

acupoints

Cramp et al192 TENS/TEAS Median Healthy Randomly, 30 individuals (15 m, 15 Increase in cutaneous blood flow

nerve/LI4 f), control (10)/TENS (10)/TEAS in the TENS median nerve

Litscher et al141 LS Vision- Healthy 15 volunteers (10 m, 5 f), LS/MA Increases in blood flow velocity

related in posterior cerebral artery

acupoints

Balogun et al193 TEAS (HVG) ST36, ST37 Healthy 11 individuals (5 m, 6 f), 2 No increase in peripheral

Hz-TEAS/120 Hz-TEAS hemodynamic functions in

asymptomatic individuals

Williams et al194 TEAS LR3, ST36, Diastolic Random, 10 individuals, Reduction of diastolic blood

LI11 hypertension TEAS/sham-TEAS non-APs. pressure for TEAS

Dunn et al.,195 TEAS SP6, LR3 Pregnant women Randomly, TEAS/control no stim Increase in frequency & strength

of uterine contractions

AEA, auricular electroacupuncture; AP, acupuncture point; ASD, acupuncture-like stimulation device; EA, electroacupuncture; ECG, electro-

cardiogram; EEG, electroencephalogram; f, female; HF, high frequency; HR, heart rate; HRV, heart rate variability; HVG, high voltage galvanic;

LA, laser acupuncture; LF, low frequency; LS, laser stimulation; m, male; MA, manual acupuncture; MBF, meridian blood flow; MS, magnetic

stimulation; stim, stimulation; TEAS, transcutaneous electrical acupoint stimulation; TENS, transcutaneous electrical nerve stimulation; US,

ultrasound stimulation.

of the studies were focused on pain and analgesia, which is similar to the percentage of MA studies focused on pain and analgesia.

The effectiveness analysis showed that the effectiveness of ES with respect to the analgesic effect, pain relief, and reduction of nausea and vomiting was confirmed by clinical trials involving > 1000 individuals and many RCTs. Based on clinical trials involving > 100 individuals, ES was effective in improving the alimentary system, improving muscle strength, reducing body weight, and treating stroke. Likewise, LS was shown to be useful for providing pain relief and in treating various addictions. Interestingly, the addiction treatment effect was confirmed by LS studies but not by ES studies.

4.1. Limitations

Our review is based on the four most influential databases, specifically Medline, PubMed, Cochrane Library, and Web of Science; moreover, we primarily analyzed Science Citation Index (SCI) or Science Citation Index Expanded (SCI-E) journal articles. The advantage of this approach is the inclusion of quality-guaranteed articles only. Laboratory experiments on animals, MA-only clinical trials, non-English-language articles, and review articles were excluded from the analysis. The details regarding device specifications or interventional designs, including stimulation strength, duration and interval, and patient and environmental conditions, were not analyzed due to space limitations.

Table 11 - Summary of studies on the treatment of various diseases with the four ASDs

Reference Stimulation Stimulation Symptom Control Effect

type site

Sun et al142 EA Bilateral PC6 OI Randomized, controlled, Treatment in attenuating OI

crossover design, EA (20)/no

EA (10)

Zhang et al196 TEAS LI4, PC6, Autistic children 76 children, TEAS (37)/no Effective for treatment of

ST36, SP6 receiving treatment (39) autistic children with

rehabilitation training passive & aloof social

interaction style

Yang et al197 TEAS LI4, SJ5, ST36, Supratentorial Randomized controlled trial, Significantly shortened

BL63, LR3, craniotomy EA/sham-EA speed of postoperative

GB40 recovery

Sahmeddini et al198 EA PC6, PC5 End-stage liver disease Randomized, 40 patients, Reduction of severity &

patients undergoing norepinephrine- incidence of hypotension

orthotropic deceased vasoconstrictor/EA during anesthesia for

donor liver liver transplantation

transplantation

Ng et al199 TEAS Bi PC6 Open heart surgery 40 patients, random TEAS Earlier return to

(20)/placebo-TEAS no stim preoperative BP, HR, &

(20) RPP values

Wang et al200 MA/EA Bi GB8, TE17, Tinnitus Randomized, single-blinded, Short-term general effects

GB2, GB20, placebo-controlled design, 50 on tinnitus (EA)

GV20, TE3, patients (46 m, 4 f),

ST36 MA/EA/placebo

(MA)/bi

GB8, TE17

O'Brien et al201 LS 10 acupoints Active symptoms of Double-blind, randomized, Treatment of menopausal

menopause placebo-controlled study, 40 symptoms (no more

women, LS/placebo LS (off) efficacious than MA)

Ngai et al202 TEAS Bi EX-B1, LU7 Patients with asthma Randomized controlled trial, 30 Reduction in the decline of

individuals, random forced expiratory volume

TEAS/TEAS + ST/sham-TEAS in 1s FEV (1) following

+ ST exercise training

Burduli & Ranyuk203 LS + ST Acupuncture Chronic noncalculous 73 patients, ST (35)/LA + ST (38) Cholecystitis treatment

points cholecystitis

Su et al204 LS Acupoints Renal failure patients Randomized controlled trial, Decrease in both stress &

receiving regular before/after LS fatigue levels

hemodialysis

Lau & Jones205 TEAS Bi Ex-B1 Chronic obstructive Randomized, Management of dyspnea

pulmonary disease placebo-controlled trial, 46

patients, TEAS/placebo-TEAS

no stim

Hsu et al206 EA BL15 Healthy 10 volunteers, sham-EA/2 Relaxation, calmness, &

Hz-EA reduced feeling of

tension or distress

Bray et al207 EA Uni PC6, HT3, Healthy 80 individuals, EA-PC6, HT3, Adjunct therapy for

LR3/bi LR3/ EA-GB34, LI11, SI3/no disorders of

GB34, LI11, stim; 5/60/100 Hz; hypervigilance (to

SI3 uni/bilateral decrease arousal levels)

Litscher et al208 LS ST7, TE22 Intensive care patient 34 volunteers (10 m, 24 f), 1 Reproducible functional

after severe head patient (head injury), changes in the brain

injury acupressure/MA/LA

O'Reilly et al209 LS SP6 Interstitial cystitis Double-blind trial, random LS Treatment & control

(29)/placebo (27) cohorts experiencing

similar improvements, no

difference between active

& sham

Li et al210 MS GV14, PC6 Healthy Randomly, 40 individuals, Effects of driving fatigue

MS/control MS non-APs

AP, acupuncture point; ASD, acupuncture-like stimulation device; BP, blood pressure; EA, electroacupuncture; f, female; FEV1, forced expiratory

volume in 1 second; HR, heart rate; LA, laser acupuncture; LS, laser stimulation; m, male; MA, manual acupuncture; MS, magnetic stimulation;

OI, orthostatic intolerance; RPP, rate pressure product; ST, standard treatment; stim, stimulation; TEAS, transcutaneous electrical acupoint

stimulation.

Table 12 - Clinical studies showing miscellaneous characteristics

Reference Stimulation type Stimulation site Symptom Control Effect

Chen et al143 LS LU9, PC7, HT7, SI4, SJ4, LI5, SP3, LR3, KI4, BL65, GB40, ST42 Healthy 76 candidates Complementary & interaction for current flow of meridians

Gopalan et al211 EA Acupuncture points Implanted with cardiac device Safety in patients with a total artificial heart

Irnich et al212 LS/Seirin (sham-LS) LI4, LU7, LR3 Healthy Randomized, double-blinded, crossover design, 34 volunteers, LS (18)/sham-LS (16) Valid placebo control in laser acupuncture studies (Seirin)

Litscher & Wang213 MA/LS LU6 Healthy 1 person, MA/LA Changes of electrical skin impedance

Thompson & Cummings214 EA Acupuncture points in a limb Healthy No detectable currents in the chest (safety)

Leung et al215 TEAS/MA/EA LI4 Healthy 15 individuals, TEAS/MA/EA Difference in electrical conductance between APs & non-APs

Litscher et al216 LS Acupuncture points Healthy 29 volunteers (9 m, 20 f), LA/placebo-LA; before/after Change in the median value of cold pain, no significant changes in parameters of thermal sensory & pain thresholds

Chang et al.,217 EA/TEAS Left LI4 Healthy 13 volunteers, 2 Hz-EA/2 Hz-TEAS/100 Hz-TEAS Changes of cutaneous reflex

AP, acupuncture point; EA, electroacupuncture; f, female; LA, laser acupuncture; LS, laser stimulation; m, male; MA, manual acupuncture; TEAS,

transcutaneous electrical acupoint stimulation.

Fig. 3 - The number of published articles on the four ASDs per year.

ASD, acupuncture-like stimulation device; ES, electrical stimulation; LS, laser stimulation; MS, magnetic stimulation; US, ultrasound stimulation.

Table 13 - Summary of studies on the effect of the four ASDs on brain activity

Reference Stimulation Stimulation Symptom Control Effect

type site

Guo et al.,144 MS PC6 Healthy 6 right-handed volunteers (3 m, 3 f) Brain activity

Zhang et al145 MS Left GB37 Healthy GB37-MS/mock point-MS Brain activity

Raith et al146 LS Bi LI4 Term & preterm 20 neonates (12 m, 8 f), LA Brain activity

neonates period/postintervention period

Quah-Smith et al147 LS LR8 Healthy 16 participants, random on-off Brain activity

block design, LA/MA

Zhang et al148 TEAS LI4, PC8 Healthy 18 individuals (9 m, 9 f), all Brain activity

individuals TEAS

Yin et al149 MS PC6 Healthy — Brain activity

Lee et al150 MS PC9 Healthy — HRV & brain activity

Litscher151 LS PC6 Healthy 40 volunteers, LA/MA Brain activity

Wu et al152 LS Palm Healthy single-blind randomized trial, 40 Brain activity

individuals (m), random

LS (20)/sham LS (20)

Litscher et al153 LS Bi PC6 Healthy (f) 1 volunteer (f), LA Brain activity

Yu et al154 MS PC6 Healthy MS-PC6/ MS-mock point Brain activity

Jiang et al., 155 TEAS LI4, PC8 Healthy 40 individuals, TEAS (40) Brain activity

Hsieh et al156 LS KI1 Healthy right 36 right-handed volunteers, Brain activity

handed random MW LA (12; 8 m, 4 f)/CW

LA (12; 9 m, 4 f)/placebo LA(12)

Yu et al157 MS PC6 Healthy before MS/during MS/after MS Brain activity

Kim et al158 MS PC9 Healthy — Vascular & brain

activity

Jo & Jo159 MS HT4, HT6 Healthy 23 young adults (aged 19-22 y) Brain activity (pole

direction)

Zyloney et al160160 EA LI3, LI4 right hand Healthy, right 48 individuals, random EA/sham Brain activity

handed EA

Quah-Smith et al161 LS LR14, CV14, LR8, HT7 Healthy 10 individuals, random Brain activity

LA/LA-sham point

Xu et al162 MS ST36, LI4 Healthy MS/MS-mock point Brain activity

Na et al163 EA GB34 Healthy 12 individuals, EA/EA-sham points, Brain activity

Xu et al164 MS ST36 Healthy Pre-MS/post-MS (0.5 Hz/1 Hz/3 Hz) Brain activity

An et al165 EA LI4, LI11 Healthy Brain SPECT EA (20)/PET EA (13); Brain activity

before/during /after EA

Wang et al166 EA Right LI4 Healthy EA (9)/sham-point EA (5) Brain activity

Zeng et al167 EA LI4 Healthy (right EA Brain activity

handed)

Litscher et al168 LS Acupoints Healthy Randomized controlled crossover Modulation of blood

trial, 18 volunteers (7 m, 11 f), flow, brain activity

before/during-LA/after

Zhang et al169 EA Left leg ST36, SP6 Healthy (right 48 individuals, 2 Hz-EA/100 Hz-EA Analgesia

handed) effect/brain

activity

Li et al170 EA TE8, GV15 Healthy (Chinese 17 volunteers (m), EA-TE8 Brain activity, typical

males) (11)/EA-GV15 (6) language areas in

the left inferior

frontal cortex not

activated

Kong et al171 EA Left hand LI4 Healthy (right 11 volunteers (6 m, 5 f), EA/MA Brain activity

handed)

Siedentopf et al172 LS Left foot BL67 Healthy (m) 10 volunteers (m), LA/dummy LA Brain activity

Wu et al173 EA GB34 Healthy 45 volunteers, EA (15)/mock-EA no Modulation of

stim (7)/minimal-EA superficial hypothalamus

& light stim (8)/sham-EA limbic system

non-Aps (15)

Chang et al174 MA/TEAS LI4 Healthy Randomly, control TEAS no Increases in

stim/MA/2 Hz-TEAS/100 amplitude of

Hz-TEAS H-reflex (TEAS),

100 Hz TEAS has

greater effect

AP, acupuncture point; ASD, acupuncture-like stimulation device; EA, electroacupuncture; f, female; HRV, heart rate variability; LA, laser

acupuncture; LS, laser stimulation; m, male; MA, manual acupuncture; MS, ma ?netic stimulation; PET, positron emission tomography; SPECT,

single-photon emission computed tomography; stim, stimulation; TEAS, transcutaneous electrical acupoint stimulation.

■ EA TEAS

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Fig. 4 - The number of articles on ES methods with years, where EAs include the invasive techniques of EA, AEA, and EHA, and TEASs include the noninvasive techniques of TEAS and TENS.

AEA, auricular electroacupuncture; EA, electroacupuncture; EHA, electrical heat acupuncture; ES, electrical stimulation; TEAS, transcutaneous electrical acupoint stimulation; TENS, transcutaneous electrical nerve stimulation.

5. Conclusions

In the past decade, modern ASDs have been studied extensively for their clinical effectiveness and to test equivalence or noninferiority with traditional MA. Among the modern ASDs, ES was found to be most widely studied, and its popularity was sequentially followed by LS, MS, and US. Specifically, EAs, which are invasive types of ES, were the first and most intensively studied types of ASDs, whereas TEASs, which are noninvasive types of ES, have surpassed EAs in publication number since 2010. Very recently, noninvasive techniques, such as TEASs, LS, MS, and US have gained research attention, as evidenced by increasing annual publications.

The most extensively studied treatment effects were for analgesia and pain relief, whereas rapid growth has occurred in the research field of the effects of treatments on brain activities. The overall quality of the study designs was moderate, as 58% of the studies were based on RCTs and 96% of the RCT-based outcomes reported therapeutic benefits. ES was effective in providing an analgesic effect, pain relief, and a reduction of nausea and vomiting, based on clinical trials involving > 1000 individuals. Based on > 100 clinical trials, ES was shown to be effective in improving the alimentary system, improving muscle strength, reducing body weight, and treating stroke. LS was effective in pain relief and for treating various addictions. We anticipate more studies on the therapeutic effects of ASDs, particularly concerning noninvasive methods, to meet the growing needs of guaranteed safety, decreased risk of infection, decreased pain, and improved convenience.

Conflicts of interest

No conflicts of interest are declared.

Acknowledgments

This work was supported by a grant (K15012) from the Korea Institute of Oriental Medicine, Daejeon, Korea, funded by the Korean government.

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