Acupuncture, Adenosine and Cycling Fish

You may have heard this story as it is all over the popular press right now. We are told that scientists have discovered some of the mechanisms underlying acupuncture analgesia. As always with alternative therapy reports the media have enthusiastically bitten off the hand of the press release (see this great account from the blog stuff and nonsense) but there is a bit of a problem and it lies at the heart of the research question. Others have beaten me to it in analysing the study and its conclusions so rather than go over all that ground again (do read the linked blogs – they sum it up brilliantly) I thought I’d just offer my perspective.

Essentially the study, published in Nature Neuroscience, found that inserting and twiddling acupuncture needles in what is described as an acupuncture point in mice with induced injuries (do mice really have their own meridian charts developed over thousands of years?) seemed to reduce pain behaviour and that this effect was closely associated with local tissue adenosine and adenosine receptor levels. No control for acupuncture was used. The authors conclude in the paper that the specific clinical effects of acupuncture for pain are in part mediated by adenosine and in the press release that the results “add to the scientific heft underlying acupuncture”. The media conclude that “scientists find why acupuncture works”.

But here’s the thing: it is not clear that acupuncture clinically has any real specific therapeutic effects to speak of as real acupuncture rarely outperforms sham in trials, even where the sham is non-penetrating. In fact it is becoming clearer that it doesn’t. Even the placebo effect of acupuncture for pain does not seem large. So if needling has an active and specific effect in the tissues it is not strong enough to be distinguished from placebo in controlled clinical trials.

So in the end it’s a bit like looking for the reasons that explain why I am so great at basketball (when everybody knows that I suck at basketball since I am only 5 foot 5inches tall and have a complete lack of talent); or studying the mechanisms by which halibut do so well in cycle races (via a study in mackerel). I have a post coming soon discussing the issues surrounding acupuncture in detail so more to follow….

Original Abstract: Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture

Acupuncture is an invasive procedure commonly used to relieve pain. Acupuncture is practiced worldwide, despite difficulties in reconciling its principles with evidence-based medicine. We found that adenosine, a neuromodulator with anti-nociceptive properties, was released during acupuncture in mice and that its anti-nociceptive actions required adenosine A1 receptor expression. Direct injection of an adenosine A1 receptor agonist replicated the analgesic effect of acupuncture. Inhibition of enzymes involved in adenosine degradation potentiated the acupuncture-elicited increase in adenosine, as well as its anti-nociceptive effect. These observations indicate that adenosine mediates the effects of acupuncture and that interfering with adenosine metabolism may prolong the clinical benefit of acupuncture.
Goldman N, Chen M, Fujita T, Xu Q, Peng W, Liu W, Jensen TK, Pei Y, Wang F, Han X, Chen JF, Schnermann J, Takano T, Bekar L, Tieu K, & Nedergaard M (2010). Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nature neuroscience PMID: 20512135

Madsen, M., Gotzsche, P., & Hrobjartsson, A. (2009). Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups BMJ, 338 (jan27 2) DOI: 10.1136/bmj.a3115

All blog posts should be attributed to their author, not to BodyInMind. That is, BodyInMind wants authors to say what they really think, not what they think BodyInMind thinks they should think. Think about that!


  1. Agreed. The effects of placebo and other higher centre modulatory effects such as past experience, desire for success with treatment, belief that it will work because Aunty Mabel had acupuncture and it relieved her pain etc (which of course can tie into placebo) are likely to be big players in the end result. I, as many others, do embrace the placebo effect generally and look to facilitate this mode of relief in combination with a variety of cognitive and enviromental ‘manipulations’ (e.g. just being interested in someone’s story for example!).
    From a modern pain perspective, if the acupuncture/dry needling brings about relief then the brain is clearly feeling less threatened by the context. Maybe attentional, distraction, tactile discriminination or all of the above, essentially all methods that I & others use commonly in the clinic.
    It’s a great debate!

  2. Neil O'Connell says

    Blimey Richmond that is some response! I don’t want to say too much as I have a larger post (written before this adenosine caper) arriving on BIM soon.

    The problem is not so much the study (although it is debatable whether there are good reasons to hunt down specific mechanisms for acupuncture at this stage) but the interpretation. The information on adenosine and its actions is interesting but the way it has been spun, not just by the media but also in the press release (and to a degree in the intro and discussion of the paper), with little consideration of the existing evidence is misleading. Patients and therapists understandably want treatments to work and want to believe they are underpinned by science and will grab hold of this kind on news with both hands.

    In terms of “slamming”, I reckon active debate and critique underpin good science and hopefully will ultimately lead to more reliable information being bandied about (he said optimistically).

  3. There’s nothing quite like an article to provoke a huge debate, and in essence this is a great thing! We do seem to default to ‘slamming’ others work so if some good can be found then we will all be happier and tweak our immune systems….
    So indeed it does seem that sticking a needle into tissue (anywhere?) can cause the release of adenosine. We understand that this purine nucleoside is involved in many physiological processes including suppressing inflammation (Manjunath & Sakhare, 2009), stimulating angiogenesis (Fedholm, 2007), wound closure (Montesinos et al., 2002), inhibition of immune cells (Sitkovsky et al., 2003), its formation triggered by injury or stress. Clearly inserting a needle covers both of these and therefore any trauma could be expected to stimulate a similar local response. Therefore it is questionable that this is a specific reaction to acupuncture or needling. In fact, as far as I understand it, there are no known specific responses to these techniques. Obviously the clarification of the application type is essential in any analysis, i.e. is this traditional acupuncture using the recognised points or dry needling where other thought systems are in process?
    From a scientific viewpoint it seems sensible to look at possible effects of creating a local albeit small trauma upon the neuraxis in its entirety, i.e. top-down and bottom-up. How does the brain perceive this overall interaction (thought of the technique understanding, past experience, views of significant others, how it is explained & applied, cultural effects, the environment, timing of the day in relation to biorhythms, anxiety & fear, expectation etc etc) and the threat value? A defensive reaction will be incurred as one would expect and clearly this includes attention to the area being treated, perhaps some local pain or discomfort, various chemicals released through the nervous system, modulation in the SC and higher centres according to some of the mentioned factors. Within this thinking there is ample room for integrating the placebo effect and the underpinning physiology of this system.
    Pain is a multisystem output and although this can be daunting it does give us a variety of ‘ins’ to modulate the activity in the pain matrix. Techniques and interventions need to take into account of the state of the nervous system, how we can influence the neuroimmune interactions, affect the functioning of the SNS to name but a few. Acupuncture could be one of these modalities and we do often see and hear about the relief after treatment. However, as scientists and clinicians we should want to know why and how and this is the problem. We don’t really know if there are any specific actions with so many variables including those aforementioned.
    So where does that leave us? Should we use acupuncture/needling or forget it? There is some really good work in the paper in terms of looking at the release of adenosine and what happens when the receptors are played with, essentially offering a treatment angle without the need for acupuncture.

  4. Neil O'C says

    More excellent coverage of this can be found here:

    Oh and if you’ve got too much time on your hands I’ve begun to reluctantly tweet! @neiloconnell