Best Acupuncture Study EVER!

Alternative Medicine
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I recently wrote on the blog about a study which I thought some here might find interesting, both for what it says about acupuncgture and for what it says more generally about the reliability of our firsthand perceptions of things. (the writeup on the blog includes links, but I didn’t bother to copy over all the urls here)
Chae Y, Lee IS, Jung WM, Park K, Park HJ, Wallraven C. Psychophysical and neurophysiological responses to acupuncture stimulation to incorporated rubber hand. Neurosci Lett. 2015 Feb 11;591C:48-52. doi: 10.1016/j.neulet.2015.02.025. [Epub ahead of print]
The researchers in this paper used a process called “incorporation," a bit of psychological sleight-of-hand (pun intended) that allowed them to create in their subjects the sensation that a rubber model of a hand was actually part of their own body. In brief, then hand subjects sit with one hand hidden from view below a table and with a rubber hand positioned where their own hand would be if it was rested on the table. They then stroked the rubber hand and the subjects’ own hand simultaneously, creating the sensory illusion that the rubber hand belonged to the subject’s body.
This is weird enough, and says some interesting things about how our brains work and how they don’t always interpret the world around us correctly. But in this experiment, the incorporation was just the first step. The investigators then performed acupuncture on the rubber hand and measured responses in a couple of ways. They asked patients about signs of what is called DeQi, a sensation associated with acupuncture that is sometimes used in acupuncture studies as a marker of treatment effects. They also looked at activity in the subjects’ brains using a functional MRI unit.
What they found was that performing acupuncture on a rubber hand that one had been tricked by a visual and tactile illusion into seeing as one’s own hand had the same kinds of effects on the subject as acupuncture practices on their real body.

The findings of the present study clearly demonstrate that acupuncture stimulation to a rubber hand resulted in the experience of the DeQi sensation when the rubber hand was fully incorporated into the body. The present study also demonstrated that acupuncture stimulation to the incorporated rubber hand was associated with brain activations in the DLPFC, insula, SII, and MT visual area. These findings are consistent with those of previous studies which found that acupuncture stimulation leads to common brain activations in the sensorimotor cortical network, including the insula and SII Although acupuncture stimulation was only applied to the incorporated rubber hand in the present study, the stimulation clearly produced similar brain activations as does acupuncture to the real hand.
Interestingly, this is not the first study showing that so-called phantom acupuncture can mimic real acupuncture, though what “real" means in this context is unclear. Though I am certain acupuncturists will disagree, what does seem clear is that if you can induce the sensations and brain activity associated with acupuncture by using needles in places not considered “real" acupuncture points, fake needles that don’t penetrate the skin, toothpicks, and now even needles poked into a fake hand not even connected to a subject’s body, the sensations and brain activity you are invoking come from the mind of the subject, not the acupuncture. What clearer definition of a placebo is there than a treatment that exerts its effects entirely through the beliefs of the subject without ever having to actually be applied to their body?
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Thanks for sharing that. I had heard of incorporation before but haven’t seen it used in this way. Since acupuncture is all about magical forces I am certain acupuncture supporters will have some magical explanation for this.

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At least from what I see in the abstract on Medline, it would be an over-interpretation to conclude from this that acupuncture is just a placebo treatment. I haven’t read the full text since it’s behind a paywall - and some of what follows may be addressed in the paper.
First, what would it mean to say that acupuncture is just a placebo?
It would mean that any pain relief or other benefits would be happening “top-down”, via consciousness, expectations, etc., rather than “bottom-up”, by a mechanism outside of the brain’s consciousness.
But:

  • The sensation of deqi, brain activations in the dorsolateral prefrontal cortex, insula, secondary somatosensory cortex, and medial temporal visual area created by needling a rubber hand, do not equate to the “effects of acupuncture”.
    If one could, say, obtain the same pain relief by needling a rubber hand as by needling the actual hand where the pain is, that would be more impressive. I’m not sure if that would demonstrate that acupuncture is acting just as a placebo in this case, because I don’t know what the brain mechanism is for incorporating a rubber hand.
  • Had the subjects received acupuncture before? People learn to have a subjective experience in response to something, and in that case the brain changes after needling a rubber hand might not be surprising at all.
  • Was the brain activation observed as much as is created by real acupuncture?
  • There were only 17 subjects.
  • Real acupuncture causes the local release of adenosine because of micro-injury caused by the needle. The adenosine release decreases the transmission of pain signals to the brain. Also this might be the mechanism for anti-inflammatory effects of acupuncture, because adenosine is anti-inflammatory. So there’s a known non-placebo component to acupuncture.
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The fact that acupuncture is a placebo is not established by a single study, of course. However, many studies have been conducted, and the balance of the evidence leads to the following conclusions:

  1. The clinical effects reported for acupuncture are almost entirely subjective symptoms (pain, nausea, etc.), and often these will be different between control and treatment groups while objective measures will be unaffected (e.g. THIS] study in asthmatics, where the sensation of symptom relief was reported but lung function measured objectively remained unchanged).
  2. These effects are often statistically significantly different while have effect sizes too small to have clinical relevance.
  3. The better the controls for bias, the less effect is typically seen, which has been established by systematic reviews of acupuncture.
  4. The effects seen with acupuncture therapy appear not to depend on where the needles are placed. This combined with the lack of consistent evidence for identifiable anatomical or functional features common to supposed acupuncture “points,” the lack of agreement among acupuncturists about where such points are, and the lack of a consistent ability for acupuncturists to repeatedly locate such points, all suggest that there are no special places where needling produces beneficial effects compared to needling at other locations.
  5. Several studies have shown that sham acupuncture, where the skin is not penetrated, has effects equivalent to “real” acupuncture.
  6. Other studies have shown that the presentation of the therapy by the acupuncturist has a strong influence on the apparent effects. When acupuncturists follow rigid scripts for how to discuss the therapy, effects can be seen or not seen based on the content of the scripts.
    All of this adds up to acupuncture being an elaborate placebo. The study I cited merely adds a layer to that, which is that you can get certain subjective sensations previously identified as “proof” of real effects from acupuncture without ever actually touching people with the needles.
    It is true that measurable physiological effects occur when you stick needles in people. Local effects, chemical mediators, and brain effects. However, this does not show that the application of fine needles at specific locations has predictable and clinically meaningful benefits. You can see local effects, chemical mediators, and brain activity in people when you bang their toe with a hammer or apply an electrical shock as well. The claim is not that needling does nothing, it is that any clinical benefits are due entirely to non-specific, that is placebo effects. Since similar placebo effects can be obtained with therapies that also have real and objectively measurable physical benefits, there is no advantage to acupuncture over such real therapies.
    Here are some additional articles you might be interested on this subject:
    Acupuncture is all placebo]
    Acupuncture is a theatrical placebo]
    some discussion of the role of adenosine] in acupuncture’s supposed effects (and MORE ADENOSINE])
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You didn’t address the reasons I gave for caution about interpreting the rubber-hand study beyond how the researchers themselves interpreted it. They were just investigating whether people could be suggested into having the de-qi sensation.
But in any case - You write

The effects seen with acupuncture therapy appear not to depend on where the needles are placed.
So then, it has equivalent effects on pain or inflammation in a given spot, if the animal or human is acupunctured anywhere else on their body? This would mean that acupuncture anywhere on the body offers pain relief anywhere else on the body. Is that what you are claiming? I haven't seen studies that support this claim. In studies of acupuncture for lower back pain, for example, have they tried acupuncturing people on their face or shoulder, say, and found that the same relief for back pain was obtained as if the people were acupunctured in their lower back? Even if the acupuncture was on the opposite side of their body? That really would suggest an effect with a central brain mechanism. What I have seen is studies where the control is acupuncture a short distance away from the acupuncture point, and there isn't a significant difference in pain relief between control and "real" acupuncture. So it may be that in some or all cases, there isn't a definite acupoint at which acupuncture should be done - but rather an acu-patch with fuzzy edges, where acupuncture causes pain relief. In the mouse acupuncture study "Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture" at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3467968/ they found that acupuncturing the mice on the contralateral leg didn't produce pain relief. They did have objective measures for pain. They said this ruled out a central mechanism. I suppose what they mean is that if the mechanism is opioid release in the little mouse brain, then acupuncture on one leg would have to influence pain in the other leg. Or if there were some other mechanism like the mouse's attention being distracted from the pain, then it should have a quite general effect. I've seen studies that found that acupuncture on the contralateral side does produce pain relief. I suppose in those cases, there has to be a central mechanism involved. A central mechanism is necessary (but not sufficient) for the placebo effect, according to the definition I'm familiar with - see the good diagram on pg 5 of "Placebo effects: Scientific advance and potential clinical and ethical implications" (available free online). Sometimes "placebo" is used to refer to a control - but the control depends on what the researchers want to investigate, and it isn't necessarily a placebo. Yes there are studies where not penetrating the skin produced the same pain relief as acupuncture did. The authors of the mouse acupuncture study say
needle penetration has been reported to not confer an analgesic advantage over nonpenetrating needle application, as opposed to our observations and those of others. However, it is possible that ATP release from keratinocytes in response to mechanical stimulation of the skin results in an accumulation of adenosine that transiently reduces pain, as A1 receptors are probably expressed by nociceptive axon terminal in epidermis. In fact, vibratory stimulation applied to the skin depressed the activity of nociceptive neurons in the lower lumbar segments of cats by release of adenosine. However, this effect differs from the anti-nociceptive effect of acupuncture, which does not depend on the afferent innervation of the skin. Acupuncture is typically applied to deep tissue, including muscle and connective tissue.
In other words, the non-penetrating control might also cause adenosine release. I looked up their reference where not penetrating produced the same pain relief as acupuncture - "Analgesic effect of acupuncture needle penetration a double"blind crossover study" One issue is that the needles weren't rotated after they were inserted. In the mouse study, acupuncture without rotating the needles didn't produce pain relief. So they were comparing a non-penetrating "acupuncture needle" to a weak version of acupuncture. It seems clear that acupuncture doesn't have a very strong effect - if it did, we'd probably know by now. I've looked at some studies of acupuncture for allergic rhinitis. One of them compared acupuncture to oral loratadine - but oral antihistamines are themselves only barely better than placebo for AR, and loratadine at the standard dose, is a weak antihistamine. So they were setting the bar for a positive result, very low. But the assertion that acupuncture works only via placebo effect, is unproven and dubious. By the way, if anyone has the full text of that rubber hand study, I'd like to look at it. I download the full text of articles at a library now and then, but I don't make it there very often.
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You didn’t address the reasons I gave for caution about interpreting the rubber-hand study
You correctly indicated that this study alone could not prove acupuncture to be only a placebo, and I agreed. I do feel this study adds evidence to support that conclusion, however, because it shows that one of the responses used to support claims that acupuncture has meaningful effects is the subjective sensations it evokes in patients, and this study suggests these are generated by the belief one is having acupuncture treatment, not by needling itself. In terms of acupuncture points, my point was that they do not exist as definable entities, and that in many studies "sham" acupuncture used as a control treatment with needling in locations other than designated acupuncture points has equivalent effects to needling at those points. This demonstrates that a central claim of acupuncturists, that the location in specific locations produces reliable effects on specific organs/tissues is not valid. HERE] is a more detailed discussion of the non-existence of acupuncture points. As for the mouse/adenosine study, I provided a couple of analyses of it. It does not validate any of the theoretical or clinical claims of acupuncture. It merely shows that sticking needles into mice can stimulate adenosine release which can blunt the response of nearby pain neurons. This is hardly compelling evidence that clinical use of acupuncture involves more than placebo effects in the face of numerous studies showing sham acupuncture has effects equivalent to real acupuncture. I agree that needling has measurable physiological effects, I just don't see any believable evidence that these effects can be controlled and targeted at particular clinical problems to produce meaningful clinical benefits.
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This is an aside but
What’s wrong with the placebo effect, if it produces real results?
I ask in light of an interesting little TED talk I listened to last night.

Is there scientific proof we can heal ourselves? | Lissa Rankin, MD | TEDxAmericanRiviera https://www.youtube.com/watch?v=LWQfe__fNbs
Now I admit she was a tad too enthusiastic for me and I'd want to know more about her examples such as Dr. West's patient - before buying into all she's says. Still, based on my own experiences I can certainly relate to the innate 'natural repair' abilities of our bodies being intimately linked to our emotional state of mind. On another level I know that my body has taken better care of me, than I have of it. So I have great respect for the notion of the body having innate abilities that go well beyond our general understanding. Thus, hearing all the stories about how the placebo effect has produced real and measurable changes in people - I wonder why it always seems to be talked about with that undercurrent of derision I see reflected in these comments?
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This is an aside but What's wrong with the placebo effect, if it produces real results? Thus, hearing all the stories about how the placebo effect has produced real and measurable changes in people - I wonder why it always seems to be talked about with that undercurrent of derision I see reflected in these comments?
There is no doubt the body can heal itself. We wouldn't be here nor would any of the planets life forms if we didn't have the ability to fight infections and heal injuries to some extent without medical intervention. There are no "magical" powers though. There are complex interactions between our nervous system and our immune system or our emotions and our perception of pain and perhaps this is what you are referring to. Convincing someone that a particular treatment will be effective may engage some of these pathways but there are drawbacks to using deceit to treat people. 1) If a treatment has a placebo effect that does not mean it helped. Lets say I have an ointment for arthritis that people swear by yet in a study it works no better than placebo. Those who felt they got improvement were experiencing the placebo effect and in all likelihood they would have gotten better without the ointment. There was no net benefit. 2) Intentionally using the placebo effect requires the health care provider to be dishonest with their patient and undermines the doctor patient relationship. 3) The placebo effect is often used to promote unscientific ideas and bogus products for profit. The belief in pseudoscience and magic harms us all. Much of the derision you see regarding the placebo effect is well deserved and comes in the setting of snake oil salesmen who use the placebo effect to profit by misleading naive consumers. This is a widespread problem today.
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The issue with placebo effects is both what are they and how do we get them? The term is used quite loosely to cover a variety of real and perceived effects that occur when a patient in a research study is getting a therapy known to not have any direct and specific physiological effect. In many cases, this amounts only to the perception of improvement in symptoms without any actual improvement in objectively measured variables. As in the asthma example, people feel like they can breath better, which sounds like a good thing. However, their actual lung function is NOT better. If they substitute a therapy that makes them feel better for one that actually improves their ability to breath, they can be experiencing harm without knowing it. Thinking you’re better when you’re not is misleading.
Another issue is that belief does produce some physiologic changes we can measure, which is often used to suggest real healing is occurring because of the belief. But this is very much like the case with acupuncture, in which the kinds of changes seen are weak and non-specific. Dropping a hammer on your toe causes changes in your body just like sticking needles in it, but this would hardly be thought an effective medical therapy. With the placebo, the changes that occur due to belief in the absence of real specific medical effects are weak and not reliable. Sure, if it makes someone’s perception of their pain a little less, that’s fine. But NOT if this leads them to eschew medicine that can truly help their condition.
Finally, placebo effects occur even when the therapy given also has real effects on the body. So there is no need to give fake therapies to get the little subjective boost that the placebo offers. We can have our cake and eat it too!

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MacGyver and McKenziev, thanks for taking the time to respond.
Those are some good thoughts to chew on.
… and yes, they make sense to me. :slight_smile:

<em>OH, just thought of another aside.
What's the origin of "Mac" vs "Mc"</em>
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MacGyver and McKenziev, thanks for taking the time to respond. Those are some good thoughts to chew on. … and yes, they make sense to me. :-) ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ OH, just thought of another aside. What's the origin of "Mac" vs "Mc"
"Firstly, it is complete and utter nonsense that Mac and Mc indicate Scottish or Irish origins. They are both EXACTLY the same word, the Mc is actually the abbreviated form of Mac (and sometimes meic) and was usually written M'c (sometimes even M') with the apostrophe indicating that the name has been abbreviated (there are many other characters indicating abbreviation including two dots under the c). "There is however one distinction you can make as far as differentiating between a name being Scottish or Irish. If it is an O' name it is always Irish (those in Scotland are mostly nineteenth century emigrations), but if it is a mac, mc or other variation it can be both Scottish or Irish!" http://www.scottishhistory.com/articles/misc/macvsmc.html
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OK so that’s that.
Interesting website.
thanks Lois.

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this study adds evidence to support that conclusion, however, because it shows that one of the responses used to support claims that acupuncture has meaningful effects is the subjective sensations it evokes in patients, and this study suggests these are generated by the belief one is having acupuncture treatment, not by needling itself.
It doesn't imply that. People are trained after awhile to have a response to something, so they can have that same response when they're only suggested into it. They are still trained, even if the original response wasn't just the result of suggestion. For example, suppose you were taking a drug that in clinical trials tends to cause drowsiness as a side effect, more than placebo did. A sedating antihistamine, say. You take this drug, you're familiar with what it does. Then you're given a placebo and you take it, thinking it's the drug. You're likely to feel drowsy. That does not mean your feeling of drowsiness from the original drug was created by suggestion. It just means your brain has been trained to have a certain reaction to the drug. That point depends on whether the people in the rubber hand study had received acupuncture before. That sort of thing is why it's important to read the actual paper. However, I would surprised if people who were naive to acupuncture would experience that de-qi feeling unless they were told what acupuncture is supposed to feel like, because it's supposed to be something different from just experiencing a needle prick. Were the subjects in the rubber hand study told what de qi feels like? In that case, perhaps people who are naive to acupuncture would experience de qi. But the abstract doesn't mention them being told what they were supposed to feel. It would be interesting to know what happens in the brain if someone experiences a needle prick, and whether it's different from that de-qi sensation. If someone naive to acupuncture were acupunctured in a rubber hand, I'd expect them to experience a needle prick, not de qi.
one of the responses used to support claims that acupuncture has meaningful effects is the subjective sensations it evokes in patients
Debunking specific arguments made by acupuncture believers is different from the question of whether it's a placebo. Very likely many of their specific arguments are wrong. That doesn't imply that acupuncture is a placebo effect (i.e., centrally mediated by the beliefs and expectations of the subject). I actually read about a study where "de qi" was not important to the effects of acupuncture. It may well be that it's not.
In terms of acupuncture points, my point was that they do not exist as definable entities, and that in many studies "sham" acupuncture used as a control treatment with needling in locations other than designated acupuncture points has equivalent effects to needling at those points.
So the argument that acupoint aren't specific - only rough areas - really rests on those other studies. And perhaps some skeptics would dismiss this mouse study because it was done on mice, not people. In the mouse study, they pretty well nailed it down that acupuncture at the Zusanli acupoint caused pain relief via release of adenosine. Acupuncture was not a placebo effect for those mice. That doesn't prove it for people, of course. The same authors did a later study "Traditional Acupuncture Triggers a Local Increase in Adenosine in Human Subjects" (full text is free online). From the abstract:
We asked here whether acupuncture in human subjects is also linked to a local increase in interstitial adenosine concentration. We collected microdialysis samples of interstitial fluid before, during, and after delivering 30 minutes of conventional acupuncture in the Zusanli point in human subjects. The interstitial adenosine concentration increased significantly during acupuncture and remained elevated for 30 minutes after the acupuncture. Acupuncture-mediated adenosine release was not observed if acupuncture was not delivered in the Zusanli point or if the acupuncture needle was inserted, but not rotated.
So there was something specific about the Zusanli acupoint, in this study. I have seen many mentions of acupuncture studies cited where acupuncture at a non-acupoint did not produce the same effect as real acupuncture. I don't think that the scientific consensus is that no acupoints are specific. Even if no acupoints are specific - if they are all acu-patches rather than acupoints - it wouldn't imply that acupuncture is just a placebo.
This demonstrates that a central claim of acupuncturists, that the location in specific locations produces reliable effects on specific organs/tissues is not valid.
Maybe some acupoints are specific and others aren't.
I just don't see any believable evidence that these effects can be controlled and targeted at particular clinical problems to produce meaningful clinical benefits.
That's different from a negative claim that acupuncture is just a placebo, though. I wonder if the skeptics who make this claim, are jumping to conclusions prematurely. It seems to be human nature to want to know things and to dislike uncertainty. I can't say for sure at this point. Maybe if I read enough of the research, I would dismiss the positive acupuncture studies just as some skeptics do. There are lots and lots of positive acupuncture studies.
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Intentionally using the placebo effect requires the health care provider to be dishonest with their patient
That isn't necessarily true - sometimes the placebo effect works even if people are told it's a placebo! Also, the patient could be told that they might be receiving a placebo, and agree to that. That isn't dishonest. That's what subjects in research studies are generally told - that they might be receiving a placebo. I agree that being dishonest with the patient is unethical and harmful. I had a doctor at one time who was deceptive in various ways. It made me very angry.
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A nice collection of thoughtful points, thank you.
Point 1. The subjects in the study had previous experience of acupuncture in a study, but the details of how much or what experiences they had are not included in the paper, and there was no control group, so it is impossible to separate out the role of operant conditioning in generating the DeQi sensation. In fact, none of the data on how this was measured is presented, only the final conclusion that it was elicited by stimulation of the rubber hand, so there isn’t much here to tell us how similar the experience was to “real” acupuncture. The fact remains, though, that the experience was generated without any actual peripheral needle stimulation, so whether it was due to operant conditioning or simple expectancy, it tells us that the sensation is not a reliable indicator of whether acupuncture is having any physiological effects beyond those generated by belief and experience in the brain. People claim that DeQi indicates effective acupuncture stimulation, but if it occurs in the absence of such stimulation than this claim is not supported.
Using your example of the drug and placebo, the same is true. If I could condition a response such as drowsiness by giving a drug and then get the same response with a placebo, it would indicate that the drowsiness was not necessarily a physiologic response to the drug but could be a placebo response. Other research would have to be done to see whether, in fact, the initial drowsiness was a specific physiological effect. In the case of acupuncture, a variety of different types of research have been done that support the interpretation that the effects seen are either placebo effects or non-specific effects of the minor physical trauma of needling which cannot be harnessed and targeted to achieve meaningful clinical benefits.
Point 2.

Debunking specific arguments made by acupuncture believers is different from the question of whether it’s a placebo. Very likely many of their specific arguments are wrong. That doesn’t imply that acupuncture is a placebo effect (i.e., centrally mediated by the beliefs and expectations of the subject).
I actually read about a study where “de qi" was not important to the effects of acupuncture. It may well be that it’s not.

A bit of moving the goalposts here. If specific arguments made to support acupuncture prove false, this doesn't in each individual case "prove" that acupuncture is a placebo. On the other hand, it does weaken the alternative hypothesis that it is an effective medical therapy. The final decision is always probabilistic and provisional, subject to re-assessment as new evidence is collected. I obviously feel the balance of the evidence has grown to best support the hypothesis that acupuncture is mostly placebo, but we can debate the specifics of that. However, the only way one addresses the issue is by addressing individual claims made in support of acupuncture, so one does not effectively or legitimately defend acupuncture by dismissing each disproved claim as insufficient in itself or irrelevant to the overall case any more than one effectively defends theism by a God of the Gaps strategy where everything proven by science not to require a deity is dismissed or deemed insufficient or irrelevant to the case of whether or not the deity exists as claimed by believers. Point 3.
I don’t think that the scientific consensus is that no acupoints are specific.
Consensus is population dependent, of course. The consensus among acupuncture believers, of course, is that specific points exist and matter, and the consensus among acupuncture skeptics is that they do not and don't. To the extent that the majority of the medical or scientific communities have an opinion (and most probably don't), it tends to be based on hearsay or haphazard experience rather than systematic review of the evidence. My claim is not that there is a scientific consensus that acupuncture points don't really exits, but that the evidence best supports the claim that they do not exist in the way they are described and claimed to exist by mainstream schools of acupuncture. Needling a specific point on the ear does not and cannot consistently be demonstrated to have meaningful clinical effects, and the points cannot be consistently identified by blinded observers as having as consistent anatomic or physiologic features despite decades of attempts to prove these things. This makes all the maps of acupuncture points, and the general claim for patterned needling, pretty much a longshot supported mostly by habit, tradition, and personal experience and generally not supported by controlled data.
Maybe some acupoints are specific and others aren’t.
Moving the goalposts again. The claims of acupuncturists are based on the fundamental principle that one can identify where to needle in order to produce specific desired results somewhere else. If this cannot be demonstrated, the whole foundation of the practice is (and has been) undermined, which goes a long way towards demonstrating it is not a truly efficacious medical treatment. As for the studies that suggest acupuncture is effective, there are good reasons to doubt many of them, just as there are good reasons to doubt a lot of studies in conventional medicine. Those are complex discussions involving how one appraises the literature, but here are a couple of good reads on the subject: Why Most Published Research Findings are False] The Problem with Systematic Reviews of Acupuncture in China] Do Certain Countries Produce only Positive Results?]