Abstract
In the field of acupuncture research there is an implicit yet unexplored assumption that the evidence on manual and electrical stimulation techniques, derived from basic science studies, clinical trials, systematic reviews, and meta-analyses, is generally interchangeable. Such interchangeability would justify a bidirectional approach to acupuncture research, where basic science studies and clinical trials each inform the other. This article examines the validity of this fundamental assumption by critically reviewing the literature and comparing manual to electrical acupuncture in basic science studies, clinical trials, and meta-analyses. The evidence from this study does not support the assumption that these techniques are interchangeable. This article also identifies endemic methodologic limitations that have impaired progress in the field. For example, basic science studies have not matched the frequency and duration of manual needle stimulation to the frequency and duration of electrical stimulation. Further, most clinical trials purporting to compare the two types of stimulation have instead tested electroacupuncture as an adjunct to manual acupuncture. The current findings reveal fundamental gaps in the understanding of the mechanisms and relative effectiveness of manual versus electrical acupuncture. Finally, future research directions are suggested to better differentiate electrical from manual simulation, and implications for clinical practice are discussed.
Introduction
D
This article is the second in a series of white papers put forth by the Board of the Society for Acupuncture Research addressing methodologic issues in the field. The first white paper highlighted paradoxes in acupuncture research, specifically the challenges presented by incongruent findings between basic science experiments and clinical trials of acupuncture efficacy, as well as by the limited evidence on the benefit of verum acupuncture relative to sham needling. 1 The present paper systematically reviews clinical trials and basic science studies that report comparisons between manual (MA) and electrical (EA) acupuncture to determine whether evidence-based conclusions can be drawn concerning the similarities and differences between these needling techniques. In addition, this article examines systematic reviews and meta-analyses that have separately assessed trials that used each of the two types of needle stimulation. The literature was searched for basic science studies, clinical trials of acupuncture, systematic reviews, and meta-analyses. Tables 1 –3 describe the search strategy and inclusion and exclusion criteria for each category.
MA, manual acupuncture; EA, electrical acupuncture; F, female; M, male; TENS, transcutaneous electrical nerve stimulation.
TX, treatment; MMSE, Mini-Mental Status Examination; T3, triiodothyronine; T4, thyroxine; FT3, free triiodothyronine; ROM, range of motion; VAS, visual analogue scale; IVF, in vitro fertilization.
Trials include those with MA and EA, with data on number of trials and number of patients not separated out.
SMD, standardized mean difference; CI, confidence interval; RR, risk ratios; WMD, weighted mean difference; SSRI, selective serotonin reuptake inhibitor.
The aim of this white paper is to evaluate a generally held but largely unexplored assumption in the field: that evidence derived from basic and clinical studies of EA and MA is generally interchangeable and can be used in a bidirectional approach to acupuncture research, translating between basic science and clinical studies. This article also discusses why it is imperative for future research to explore the relative clinical benefits and modes of action of MA versus EA to better inform clinical practice, and research guidelines to more directly compare these treatment modalities are proposed.
Comparisons of MA and EA: Distinct Challenges for Basic and Clinical Research
Clinical research comparing the effectiveness of MA and EA asks a pragmatic question: Which treatment works better? This is a broad but clinically relevant question. Basic research comparing MA and EA, on the other hand, asks: Does stimulating a needle manually cause the same, or different, physiological effects than stimulating it electrically? This is specific question whose direct relevance is primarily scientific.
In basic research, experimental variables need to be “isolated,” such that any difference in outcome between two treatments can be ascribed to the variable that is being examined, as opposed to some other factor. In clinical trials of acupuncture, manual needle stimulation techniques are nearly always applied for a much shorter duration than is electrical stimulation (i.e., seconds rather than minutes). Even when manual stimulation is repeated a few times at intervals during the treatment, the total duration of active stimulation is much shorter in MA than EA. Furthermore, MA and EA are not always clearly separated. For example, in a study of EA, manual stimulation is frequently performed briefly first to “obtain
From a scientific perspective, confounders can arise when the effect of a treatment is compared across two conditions in the presence of another variable that also systematically differs across the two conditions. For example, if one compares the physiologic effects of walking for 5 minutes with that of running for an hour, one could not conclude that walking and running had different effects because, in this experiment, the type of exercise would be confounded with its duration. An analogous situation occurs in acupuncture research that compares continuous electrical stimulation for the duration of the treatment (about 20 minutes) versus intermittent manual stimulation (every few minutes, for just a few seconds) or just initial manual stimulation. If a difference were observed in some physiologic measurement (e.g., blood flow indicating brain region activation) between the two conditions, one could not conclude that this difference was due to the type of stimulation (manual versus electrical) because this was confounded by the duration (20 minutes versus a few seconds) or by the periodicity (intermittent versus continuous) of the stimulus. To answer this question, manual versus electrical stimulation would need to be performed for the same amount of time and periodicity (e.g., 10 seconds of stimulation every 5 minutes for 20 minutes).
A commonly heard rationale for comparing acupuncture stimuli of different durations is that while electrical stimulation is typically applied for at least 15–20 minutes, continuous MA for this amount of time is not done clinically because continuous manual stimulation would be too painful (while continuous electrical stimulation can be better tolerated because its intensity is adjustable). However, experiments in humans or animals comparing manual versus electrical stimulation for a short duration (e.g., 10 seconds total) would be feasible as well as scientifically important. Experiments in anesthetized animals comparing manual versus electrical stimulation for longer durations (e.g., 20 minutes) also would fulfill these criteria. Unfortunately, as shown below, few such experiments have been published to date.
It is important to stress that the duration of manual versus electrical stimulation is not simply a nuisance to be dealt with methodologically. Ample evidence from basic studies of cell signaling, gene expression, and tissue plasticity suggests that the duration of a stimulus (from milliseconds to minutes to days) profoundly affects its biological function. Furthermore, habituation and refractoriness to further stimulation are well-described phenomena indicating that “more is better” does not always apply in physiology. Controlling the duration of MA or EA needle stimulation, as well as comparing the effects of different stimulus durations, should improve understanding of their physiologic effects. Furthermore, careful consideration of what is meant by “stimulation” is important as well. Electrical needle stimulation is typically continuous, while manual stimulation is brief or intermittent, with the needles left in place in between periods of stimulation. One could hypothesize that the tissue is still “stimulated” by the presence of the indwelling needle, even in between periods of manual needle manipulation. This type of stimulation could include static stretching of tissue that has wrapped around the needle and remained stretched after the manipulation stops. It is therefore imperative that these potential effects be tested while controlling one variable at a time.
In contrast to basic research, comparative effectiveness clinical research can readily ask whether prolonged electrical stimulation (treatment A) is more clinically effective than brief manual stimulation (treatment B) because in this case one is simply asking, Which treatment works better? However, an important caveat to this question is that if differences were found between the treatments, one would not know whether this had anything to do with the electrical stimulation.
Brief History of MA and EA
Descriptions of manual acupuncture techniques date at least as far back as the
The early 1970s interest in acupuncture in the United States and Europe led to Western studies of both MA and EA for experimental pain. 9,10 Identification of the endogenous opioids in the mid-1970s led to pioneering animal research by Pomeranz in Toronto 11 and Han in Beijing. 12 This research, implicating endogenous opioids in EA-induced analgesia, set the stage for the use of EA to explore a wide range of biochemical and physiologic correlates of acupuncture treatment. 13 –16 Clinical trials of EA soon followed, with publications first appearing in the early to mid-1980s. 17 –20
Current Patterns of Use
Patterns of use of MA versus EA vary greatly by condition treated, practitioner preference and training, and stimulation parameters. Needling techniques, whether MA or EA, are widely heterogeneous. Manual stimulation techniques may include rotation of the needle in one or both directions and lifting and thrusting of the needle in myriad combinations. These techniques may range from subtle and barely perceptible to vigorous, rapid, and forceful.
7,21
–27
EA techniques vary by stimulation amplitude, frequency, waveform, and duration. Clinically, EA is often performed after the needle has been manually stimulated sufficiently to obtain
A recently published survey of practitioners compared acupuncture patterns of use in the European Union (
Analyses of surveys and insurance claims in the United States indicate that EA is used in 12–15% of all acupuncture treatments. 29,30 When treating chronic back pain, the reported use of EA in the United States increases to 24–32%. 31 The decision to use EA appears to be practitioner dependent: Thirty-five percent of United Kingdom acupuncturists reported never using EA, while 13% reported using it “most or all of the time.” 32 Finally, use of EA appears to be based on the perception that it will improve clinical effectiveness in patients with more severe conditions or those more resistant to treatment. In a survey of United States acupuncturists treating chronic low back pain, 51% of practitioners reported using EA because “something simpler hadn't worked.” 33
Physiologic Effects of Manual Versus Electrical Needling Stimulation
In basic science animal studies, both MA and EA have been observed to activate all four types of afferent nerve fibers.
34
These fibers include the thick myelinated Aα and Aβ fibers, the thin myelinated Aδ fibers, and the thin unmyelinated C-fibers, all of which innervate skin and muscle. The innervation of fascia is less well known but is thought to include abundant nociceptors.
35
Single afferent fiber recordings found predominantly C and A fiber activation in response to both EA and MA.
36
However, from a broader physiologic perspective there is reason to suspect different physiologic responses to manual versus electrical stimulation of acupuncture needles. As the acupuncture needle traverses the epidermis, dermis, fascia, and muscle it contacts multiple tissues and cell types, and it is reasonable to suspect that these differing tissues and cells respond differently to electrical current added to an indwelling metal needle versus manual needle stimulation alone. For example, EA may depolarize the resting membrane potential of neighboring excitable cells that in turn could lead to action potentials along peripheral nerves and subsequent signaling cascades. On the other hand, manual manipulation of the needle, typically including lifting and thrusting to elicit
For this component of the white paper, the basic science peer-reviewed literature was systematically searched for acupuncture research studies that specifically compared electrical and manual stimulation with respect to biological outcomes (see Table 1 for search strategy). Given the wide breadth of possible outcomes to investigate, the main domains of interest were limited to animal and human experimental studies that evaluated: (1) peripheral receptors and their ligands; (2) cardiovascular responses, including blood pressure; (3) central nervous system effects, including brain-based outcomes; and (4) subjective outcomes in experimental settings, such as pain reports.
Thirteen physiological studies (5 in animals, 8 in humans) met our selection criteria (Table 1). 36,39 –51 Significant heterogeneity existed across studies, with variability in needle insertion location, electrical stimulation frequency, and stimulation duration. In searching for studies that compared the two stimulation modalities while controlling for confounding factors such as needle location, insertion depth of needle, and treatment duration, it was discovered that the duration of needle stimulation during EA was nearly always much longer than in MA (e.g., 15–30 minutes for EA and a few seconds for MA).
Moreover, most studies failed to specify whether they were directly comparing EA versus MA or whether EA was studied as an addition to MA. For instance, EA can be performed with needles simply inserted or both inserted and manipulated to achieve
In one study, EA and MA performed at the same frequency (2 Hz), location, and duration had nearly identical effects on centrally driven sympathetic nervous system activity (decreased blood pressure in a hypertensive rodent model). 36 However, some studies did report differences between EA and MA. In two human studies, EA evoked a transient decrease in temperature that was not seen in MA, 39,40 and the authors suggested that the cooling with EA could be a vasomotor spinal reflex response. More recent data from functional magnetic resonance imaging studies of healthy humans, in which stimulus duration (continuous manual stimulation and time of EA) was matched between conditions, showed greater activation in the somatosensory cortex with EA; in contrast, MA resulted largely in the deactivation of limbic system structures. 42,44 These findings were substantiated by a recent meta-analysis of acupuncture functional magnetic resonance imaging studies, which noted that while multiple areas were activated by both, EA produced greater activation in primary somatosensory cortex while MA produced greater deactivation in the putamen. 52
With respect to behavioral responses in humans, three separate studies noted significant differences between EA and MA for analgesic responses to experimental pain stimuli. While EA had a greater effect than MA for pin-prick pain, thermal and mechanical (i.e., pressure stimuli) behavioral tests did not show differences between EA and MA, 47 suggesting that the analgesic effects of EA and MA may have overlapping but not identical mechanisms, similar to the neuroimaging findings above. Further, in healthy humans significantly greater analgesia for EA was observed compared with MA, with the analgesic effect of EA occurring immediately following treatment and peaking hours after needle removal. 48 This last finding is of significance because no other studies reported outcomes hours after needle removal, which raises the possibility that the window of observation needed for determining analgesic effects of EA may need to extend long after treatment. Finally, a recent study looking at mechanical pressure pain found EA superior to MA at increasing pain thresholds in healthy humans. 49 Of note, not all human experimental pain studies identified in our search showed differences between EA and MA. For example, no difference was reported between EA and MA for experimental thermal pain. 43
Overall, while modest evidence suggests a potential difference between the physiologic effects of electrical and manual stimulation of acupuncture needles, the very small number of studies in which needle stimulation method was not confounded by other factors and the variability in methods used greatly reduce the ability to extend findings outside of individual research reports and to draw generalizable conclusions.
Clinical Trials Comparing MA and EA
The literature on randomized controlled clinical trials of acupuncture was searched to identify comparative effectiveness research on MA versus EA. The aim was to assess whether the clinical trials data reflect survey data on patterns of use of these needle stimulation techniques.
The literature search from inception through December 31, 2012, initially identified 118 randomized controlled trials published in English, of which 17 met our selection criteria (see search strategy in legend to Table 2).
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–69
Next, trials that used EA adjunctively to MA (designated as MA versus MA+EA) were differentiated from trials that directly compared the two procedures (MA versus EA). If all procedures in the EA group before electrostimulation were the same as procedures in the MA group (e.g.,
In clinical trials for pain conditions, better analgesia appears to be obtained when prolonged electrical stimulation is added to manual stimulation compared with brief or intermittent manual acupuncture needle stimulation alone. However, too few randomized controlled trials specifically assessed this question to draw robust conclusions. Most of these trials included few participants (range, 21–157) and their findings may not be generalizable. More specifically, clinical differences between MA and MA augmented by EA may depend on the location of acupuncture points (e.g., ear versus body), patient population (e.g., elderly versus young athletes), condition (e.g., back pain versus headache), and cause of pain (e.g., inflammation versus neuropathy).
Systematic Reviews and Meta-Analyses on MA Versus EA
In addition to examining individual clinical trials, we explored the literature to assess whether systematic reviews and meta-analyses might shed light on the relative effectiveness of MA and EA (search strategy included in Table 3). 70 –76 Of the 188 identified reviews, 89 met our initial inclusion criteria. Of these 89 reviews, 15 did not pool data in a meta-analysis, so that no quantitative comparison was conducted, and only 7 of the remaining reviews presented pooled data that included a quantitative comparison of outcome for MA and EA. These 7 were meta-analyses that used quantitative methods to pool trial data either comparing MA with EA in the same analysis (a direct comparison) or comparing MA versus controls with EA versus controls in 2 separate analyses (an indirect comparison).
Of the 7 reviews, only 1 included a direct comparison of MA versus EA.
70
In this analysis, through a statistical test for an interaction, acupuncture for osteoarthritis using EA (pooled effect from 4 trials,
In summary, the identified systematic reviews and meta-analyses provided limited pooled data relevant to the aims of this white paper. From 89 eligible systematic reviews, there were only 1 direct quantitative comparison of MA versus EA, which suggested that EA might be superior to MA for treating pain in knee osteoarthritis, and 6 indirect comparisons that were inconclusive. Thus, the evidence from systematic reviews on the comparative effectiveness of MA versus EA is difficult to interpret. Most clinical trials within the reviews are underpowered, and therefore any subgroup analysis conducted within trials is even more likely to be underpowered.
Conclusions and Recommendations
Research on both manual and electrical acupuncture is typically lumped together to constitute scientific evidence on “acupuncture.” However, the following important question is rarely addressed: Is there a fundamental difference between stimulating manually and electrically?
This white paper was motivated by the recognition of two areas of weakness in the acupuncture evidence base. First, models of the mechanisms of action of acupuncture are often based on basic science studies using solely EA or MA without rigorous testing of whether the physiologic effects are similar in both cases. Second, clinical recommendations and individual practitioner decisions for when to use EA or MA are based far more on clinical experience than on clinical research.
This review of 40 years of acupuncture research explored differences between manual and electrical modes of stimulation. Very few clinical trials have directly compared MA to EA stimulation, and meta-analyses have often been performed across a broad spectrum of clinical trials of acupuncture without discriminating between the two stimulation techniques. Furthermore, in basic science studies directly comparing the effects of MA versus EA stimulation, the mode of stimulation has almost always been confounded by the stimulus duration (i.e., a few seconds for MA versus 15–30 minutes for EA). Whenever manual and electrical acupuncture have been compared in basic research, the main concern of researchers has been to compare treatments that are clinically relevant rather than design experiments in which the mode of stimulation (MA versus EA) is not confounded by some other factor. In other words, in basic science, clinical relevance has systematically trumped scientific rigor. It is therefore important to recognize that while comparing physiologic effects of manual acupuncture to an electrical stimulus of identical duration may not be clinically relevant, it is of scientific importance. Controlling for stimulus duration may require testing shorter EA durations to match the duration of the MA stimulus, assuming prolonged MA is not feasible. Controlling the frequency of stimulation also may require lower frequencies of electrical stimulation, such as 2 Hz, a frequency that can be achieved with manual manipulation. Controlling other factors with high-tech solutions, such as robotics or mechanical devices to standardize needle placement, rotation, and duration, might also be beneficial and necessary.
In contrast to basic science experiments, comparing two different clinically relevant methods of delivering acupuncture (i.e., short-duration MA and prolonged EA) in clinical trials is valid as long as the aim is truly comparative effectiveness: that is, pragmatically asking what works best with no attempt at understanding why. If it is found, for example, that electrical stimulation for 20 minutes produces greater clinical improvement than 20 minutes of MA during which the needles are manipulated for only a few seconds at the outset, one cannot conclude that the electrical current itself was responsible for the difference in clinical improvement between the two methods. Moreover, mechanisms identified from basic research using EA (e.g., neurophysiologic basis of pain) cannot be assumed to be relevant to clinical trials that use MA. Unless this is specifically emphasized, the tendency to attribute clinical benefits to the electrical stimulation will remain, which will perpetuate the current level of confusion. However, as long as one remains conscious of these caveats, pragmatic recommendations for clinical practice can be based on the comparative effectiveness of EA and MA.
Finally, patterns of use, which differ widely among practitioners, should be more thoroughly explored. EA is commonly added as an adjunct to MA, and the decision to include EA in a treatment is based on numerous factors, including condition treated, severity of symptoms, individual patient differences, and practitioners' preference and training. It is of fundamental interest to understand what should guide clinical decision-making (e.g., when to include EA and what specific stimulation parameters to use to learn from clinical observations what seems to work best for particular patients and specific conditions, as well as to assess patients' experiences with EA versus MA). Finally, criteria informed by the clinical experience of both practitioners and patients, obtained through well-designed surveys and focus groups, should be developed and applied to inform the design of clinical trials comparing EA versus MA.
Footnotes
Author Disclosure Statement
No competing financial interests exist.