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Clinical trials of effectiveness
This participant-blinded randomised controlled trial (RCT) from Korea (n=68) compared acupuncture points with adjacent undefined points for upper abdominal pain and discomfort.
Sixty-eight patients with functional dyspepsia, as defined by Rome-II criteria, were randomised into two groups: 11 needles inserted either into six classical points (CV12, LI4, LR3, ST36, PC6 and SP4) or into undefined points about 1 cm away from those points. Six sessions were given over 2 weeks. To assess the effects of acupuncture, symptoms and quality of life were scored according to the Nepean Dyspepsia Index before and after acupuncture treatments. This Index assesses frequency, intensity and bothersomeness of symptoms.
Acupuncture treatment significantly decreased the dyspepsia symptoms and improved the quality of life. There was no statistical difference between the acupuncture groups treated at classical and undefined points (see figure 1).
The authors conclude that both acupuncture at classical points and undefined points improved the symptoms of patients with functional dyspepsia. But without a no-treatment control group, we do not know if there is a ‘general’ needle effect in this condition, or whether the changes were due to ‘placebo’. However, an untreated control group might be biased, because they would have liked acupuncture. Maybe placebo medication might be one option for a future study? In any case, this study provides further evidence that precise point location is not important for treating dyspepsia: so this study cannot be considered to be ‘sham controlled’.
Menopausal hot flushes
This RCT compared acupuncture with advice for hot flushes in women (n=175) with natural or induced menopause.
A multicentre, randomised, controlled trial was conducted. Perimenopausal or postmenopausal women with average hot flash scores of 10 or higher during the week before the screening visit were enrolled and randomly divided into two groups. Follicle-stimulating hormone and serum oestradiol levels were measured to confirm whether participants were perimenopausal or postmenopausal. The treatment group received 12 sessions of acupuncture and maintained usual care for 4 weeks, whereas the control group underwent usual care alone. Acupuncture was given at ST36, SP6, LI4, PC6, HT7and HT8 bilaterally, and CV4. Hot flash scores were calculated by multiplying frequency by severity of hot flashes recorded in a daily diary. The primary outcome was the mean change in the average 24 h hot flash score at week 4 from baseline. The secondary outcome was the mean change in menopause-related symptoms as estimated by the Menopause Rating Scale questionnaire at week 4. Follow-up assessment at week 8 was conducted in the treatment group only.
The mean change in the average 24 h hot flash score was −16.57 in the treatment group (n=116) and −6.93 in the control group (n=59), a difference of 9.64 (p<0.0001), see figure 2. The total Menopause Rating Scale score, as well as the subscale scores for the psychological, somatic and urogenital dimensions of menopause, showed significant improvement in the acupuncture group compared with the control group (p<0.001). The mean change in the treatment group in the primary outcome was −17.58 at week 8.
These results show an effect the same order of magnitude as the earlier ACUFLASH study. The response was quicker, probably because treatment was given three times per week. Interestingly, the control group were given the option of a course of acupuncture after 4 weeks. Only 43 of the 59 accepted, and the size of their benefit was considerably less than those who had acupuncture straightaway. This may have been due to the fact that their baseline value had reduced by then through natural history.
In a cautious discussion, the authors reveal why they randomised women on a 2:1 ratio: “practical issues such as limited funding and uncertainty in the anticipated recruitment number of trial participants” which could have been better dealt with by piloting the recruitment rate first.
This section includes a long-awaited systematic review that is of major relevance to acupuncturists because they frequently treat musculoskeletal pains including osteoarthritis (OA). But the impact and discussion about this review will involve not just the results, but the questions it addresses. There is an increasing debate about the direction of future research into chronic pain, and into acupuncture. I urge readers to consider this review along with the following summary of a very different kind of paper. As usual, I shall label my own comments so they are clearly separate from the actual report of the review's results.
Cochrane Review: acupuncture for osteoarthritis
This systematic review included 19 trials of acupuncture.
Main results (text imported from the review)
Sixteen trials involving 3498 people were included. Twelve of the RCTs included only people with OA of the knee, three only OA of the hip, and one a mix of people with OA of the hip and/or knee. In comparison with a sham control, acupuncture showed statistically significant, short-term improvements in OA pain (standardised mean difference −0.28, 95% CI −0.45 to −0.11; 0.9 point greater improvement than sham on 20 point scale; absolute per cent change 4.59%; relative per cent change 10.32%; 9 trials; 1835 participants) and function (−0.28, −0.46 to −0.09; 2.7 point greater improvement on 68 point scale; absolute per cent change 3.97%; relative per cent change 8.63%); however, these pooled short-term benefits did not meet our predefined thresholds for clinical relevance (ie, 1.3 points for pain; 3.57 points for function) and there was substantial statistical heterogeneity, see figure 3.
Additionally, restriction to sham-controlled trials using shams judged most likely to adequately blind participants to treatment assignment (which were also the same shams judged most likely to have physiological activity), reduced heterogeneity and resulted in pooled short-term benefits of acupuncture that were smaller and non-significant.
In comparison with sham acupuncture at the 6 month follow-up, acupuncture showed borderline statistically significant, clinically irrelevant improvements in OA pain (−0.10, −0.21 to 0.01; 0.4 point greater improvement than sham on 20 point scale; absolute per cent change 1.81%; relative per cent change 4.06%; 4 trials; 1399 participants) and function (−0.11, −0.22 to 0.00; 1.2 point greater improvement than sham on 68 point scale; absolute per cent change 1.79%; relative per cent change 3.89%).
In a secondary analysis versus a waiting list control, acupuncture was associated with statistically significant, clinically relevant short-term improvements in OA pain (−0.96, −1.19 to −0.72; 14.5 point greater improvement than sham on 100 point scale; absolute per cent change 14.5%; relative per cent change 29.14%; 4 trials; 884 participants) and function (−0.89, −1.18 to −0.60; 13.0 point greater improvement than sham on 100 point scale; absolute per cent change 13.0%; relative per cent change 25.21%).
In the head-on comparisons of acupuncture with the ‘supervised OA education’ and the ‘physician consultation’ control groups, acupuncture was associated with clinically relevant short-term and long-term improvements in pain and function. In the head on comparisons of acupuncture with ‘home exercises/advice leaflet’ and ‘supervised exercise’, acupuncture was associated with similar treatment effects as the controls. Acupuncture as an adjuvant to an exercise based physiotherapy programme did not result in any greater improvements than the exercise programme alone. Information on safety was reported in only eight trials and even in these trials there was limited reporting and heterogeneous methods.
Sham-controlled trials show statistically significant benefits; however, these benefits are small, do not meet our predefined thresholds for clinical relevance, and are probably due at least partially to placebo effects from incomplete blinding. Waiting list-controlled trials of acupuncture for peripheral joint OA suggest statistically significant and clinically relevant benefits, much of which may be due to expectation or placebo effects.
Results summarised by reviewer
Acupuncture is superior to sham acupuncture, for reducing pain and improving function, in both the short term and the long term. The difference is small (and the reason for that is open to debate) and almost disappears at 6 months, though not quite. Acupuncture is superior to waiting list, which is open to different interpretations. Acupuncture has a similar effect to exercise, which is recommended by the National Institute for Health and Clinical Excellence (NICE).
In my view, there is a serious misunderstanding right at the heart of this review. Sham controlled trials do not test for clinical relevance: they test for a biological effect.
Acupuncture has powerful psychological effects, like other physical therapies. It is right to raise the question whether the needles have a biological effect, in addition to the psychological effect. The answer is yes: it is hereby demonstrated that acupuncture is superior to sham for knee pain (p=0.0002). The size of that superiority is irrelevant to patients, because they are not being offered sham acupuncture. Patients need to know how acupuncture compares with other available treatments. That is what ‘clinical relevance’ means.
For patients, the important result of this review is that acupuncture has at least as good an effect as exercise, see figure 4. Exercise is recommended by NICE, and please note that the effect of exercise is measured against usual care, not against placebo, so includes the added psychological effects of a physical therapy. There is also solid evidence that acupuncture is superior to guideline based usual care: it is likely that patients who were randomised to usual care were somewhat biased against it—but that is the reality of the current situation in western culture.
It is entirely justifiable to have a debate about the data in figure 3, and most people would probably agree that the data do not look particularly ‘robust’. That debate is completely separate from the one about the clinical relevance. Looking at the trials, we note that if there was no real difference between acupuncture and sham, you would expect half of the studies to show that sham acupuncture is superior. But actually, none show that. Two studies (by Vas et al and Sangdee et al) showed a large significant effect of acupuncture over sham: the authors comment that the shams could have been unconvincing (and this was not checked at the time). But on the other hand, these were the only studies that used intensive electroacupuncture (EA), which may be the optimal form of treatment.
Our business is patient care. This review might be very elegant and detailed, but it is unfortunately, not very accessible. It runs to 142 pages, and the abstract alone is 608 words. Most readers will get the gist of it from the headline, and the tone and terminology are all too accessible: ‘Acupuncture for osteoarthritis is very like to be only a placebo’. This review could do serious damage to patient care.
But this review is not all black: it does point out that non-steroidal anti-inflammatory drugs don't meet the criteria for clinical relevance either. Oops!
Masterclass in musculoskeletal research
Where the previous review is brim full with science, this one is full of wisdom and humanity. Musculoskeletal problems are very common but patients who have them often do not get the attention they deserve because their lives are not threatened. We don't actually understand a lot about the ‘disease’ of OA, and in fact, it is not helpful to see OA as a disease at all: its effect on the patient rarely corresponds with the severity according to objective measures, but much more on psychosocial factors.
Instead of the medical model (like an infection or appendicitis), the ‘major concern about OA is the persistence and recurrence of symptoms and disability that disrupt life in the long term’. That is what patients need addressed: and we do not need very sophisticated tools to make quite a difference. One thing we do need is a shift in perception, among both healthcare staff and patients, away from the idea that ‘nothing can be done’. But this has to be balanced by a shift away from over-medicalisation (including the emphasis on diagnosis, and over-dependence on passive therapies such as drugs and, of course, acupuncture or manipulation) towards simple solutions such as weight control, exercise and work.
Expanding on that theme, the authors state: ‘Musculoskeletal problems have in common with psychological illnesses the idea that the ‘placebo’ effect is not only strong but also desirable.’ There is growing evidence that the effects of the consultation, the context, the sense of doing something have a bigger effect than the specific effects of any therapy, and ‘can be harnessed as an important part of clinical care’. The authors are hopeful that there is also growing acceptance of that fact.
NICE decided to recommend acupuncture for treatment of low back pain despite doubts about the effectiveness of its defining feature—penetration by a needle. This evidence may also concern the practitioners: ‘A challenge of implementing research about pain relief is how to introduce the idea of evidence-based uncertainty about a treatment without undermining the beneficial effect of the patient-clinician interaction.’
This review is a position paper from the Arthritis Research Campaign National Primary Care Centre in Keele, and should be influential. It points forward to a more realistic understanding of what will really help patients. It puts back humanity into caring, and is an intriguing contrast to the previous review.
It challenges me to reconsider one of my own fundamental tenets: that it is necessary to demonstrate that acupuncture needles have a biological effect (over and above their psychological effect) in order to justify using them, ethically.
Low level laser for neck pain
This journal rarely carries articles on low level laser therapy (LLLT), but it does overlap with acupuncture to a limited extent. The studies (n=16) included in this review mainly used laser irradiation of tender or trigger points: just two studies used acupuncture points—though of course these may be the same.
The authors searched computerised databases comparing efficacy of LLLT using any wavelength with placebo or with active control in acute or chronic neck pain. Effect size for the primary outcome, pain intensity, was defined as a pooled estimate of mean difference in change in mm on 100 mm visual analogue scale.
Sixteen RCTs were identified, including a total of 820 patients. In acute neck pain, results of two trials showed a relative risk (RR) of 1.69 (95% CI 1.22 to 2.33) for pain improvement of LLLT versus placebo. Five trials of chronic neck pain reporting categorical data showed an RR for pain improvement of 4.05 (2.74–5.98) of LLLT. Patients in 11 trials reporting changes in visual analogue scale had pain intensity reduced by 19.86 mm (10.04–29.68). Seven trials provided follow-up data for 1–22 weeks after completion of treatment, with short-term pain relief persisting in the medium term with a reduction of 22.07 mm (17.42–26.72). Side-effects from LLLT were mild and not different from those of placebo.
A distinct dose-response pattern was noted for each wavelength for which LLLT is effective within a narrow therapeutic window. For 820–830 nm, mean dose per point ranged from 0.8 to 9.0 J, with irradiation times of 15–180 s. For 904 nm doses, mean dose per point was 0.8–4.2 J, with irradiation times of 100–600 s. Investigators who used doses outside the minimum (0.075 J and 0.06 J) and maximum (54 J) limits of these ranges did not show any effect of LLLT, lending further support to a dose-dependent response for LLLT in neck pain.
These results are impressive. Not only is there an effect of laser, but it is dose-dependent—a biological gradient is strong supportive evidence of a biological effect. The authors summarise the current evidence in favour of three possible modes of action: anti-inflammatory effect, reduction of oxidative stress, and inhibition of transmission at the neuromuscular junction. We have to be clear that the LLLT effect may be different from the acupuncture needle effect.
The size of the effect is impressive and compares favourably with other interventions for neck pain. This review is not directly relevant to conventional acupuncture practice, but may be relevant to improving patient care. Laser is obviously more convenient, both for the patient and for the researcher!
Acupuncture and the chronic pain model
Chronic pain involves central sensitisation. Central sensitisation develops from ‘temporal summation’, that is, when repeated stimuli cause added effects. This study could be the first that specifically tests acupuncture's effect on a model of central sensitisation—the temporal summation thresholds.
Thirty-six pain-free volunteers were randomised into one of the three groups: EA (2/100 Hz), manual acupuncture with stimulation 10 times, or sham acupuncture consisting of stimulation with the guide tube followed by taping of a needle to the skin, attached to a non-functioning EA machine. Acupuncture intervention was on ST36 and ST40 on the dominant leg delivered by an acupuncturist blinded to the outcome assessment. Both subjects and the evaluator were blinded to the treatment allocation. Pain thresholds to a single pulse (single pain threshold) and repeated pulses electrical stimulation (temporal summation threshold) were measured before, 30 min after and 24 h after each treatment.
The baseline values of three groups were comparable. Compared to sham, EA significantly increased both single pain threshold and temporal summation threshold immediately after the treatment on the treatment leg as well as 24 h after on both the treatment and non-treatment legs (analysis of variance, p<0.05), as shown in figure 5. Manual acupuncture also increased single pain threshold and temporal summation threshold, but the changes were not significantly different from those induced by sham acupuncture.
To our knowledge, this is the first study that examines the effect of acupuncture on temporal summation of pain in humans. Our results indicate that EA of 2/100 Hz induces a significant analgesic effect expressed mainly in the same spinal segment of the acupuncture site and the effect becomes more potent 24 h after the intervention. In addition, we found no significant differences in the changes of single pain threshold and temporal summation thresholds in the EA group, indicating a similar mechanism underlying the analgesia of EA on these two types of pain threshold. This effect needs to be verified with heat or mechanical pain models, and in pain patients.
This is fascinating research. The bilateral raised pain threshold, which gradually increases over the first day, supports the hypothesis that EA activates descending inhibition, through release of opioid peptides.
Limitations to MRI studies of acupuncture
Basically, fMRI studies of acupuncture generally show changes in the brain activity, but disagree on whether it is increased or reduced. This research team offers a way forward. The problem is that the signal is measured repeatedly in on and off states. This summary is not for the faint-hearted.
When studying the neural responses to acupuncture with a block-designed paradigm, its temporal dynamics predicted by the general linear model (GLM) conforms to typical ‘on–off’ variations during a limited period of the experiment manipulation. Despite a lack of direct evidence associating its psychophysiological response, numerous clinical reports suggest that acupuncture can provide pain relief beyond a needling session. Therefore, a typical GLM analysis may be insensitive or inappropriate for identifying altered neural responses resulting from acupuncture.
The authors developed a new approach to investigate the dynamics underlying sustained effects of acupuncture. Specifically, they designed two separate models to evaluate the baseline activities (prior to stimulation) and neural activities in sequential epochs, using three block-designed functional runs: acupuncture at acupoint ST36, non-meridian point stimulation and a visual task. We found that the activity patterns during rest were associated with the stimulus types and that the resting activities might be even higher than that of stimulation phases. Such effects of the elevated activity during rest may reduce or eliminate the activity during stimulus conditions or even reverse the sign of brain activation using conventional GLM analysis. Moreover, such sustained responses, followed by acupuncture at ST36 and non-meridian point, exhibited distinct patterns in wide brain structures, particularly in the limbic system and brainstem. These findings may pose great implications for the design and interpretation of a range of acupuncture neuroimaging studies.
Provenance and peer review Not commissioned; not externally peer reviewed.
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