To explain the title it is a piece of the most complex and interesting senteces I've been able to casually use in conversation thus far. Someone said that Lima was cold and I said 'Frio para mi no es como frio para ti' which rougly translated to 'Cold for me is not like cold for you'. If someone out there reads this and has corrections please keep them to yourself. I'm proud of that one. I've l
Monthly Archives: June 2010
fireside thoughts
may 31 2010. one day segues into another and i find sleep is a bland space between two lives. i sat fireside at the cottesloe hotel and watched the sun slide down the clouded sky into the sea. i love the space the void the quiet emptiness that is western australia. the pub was virtually empty. monday nightpoker being setup for seven. the day passed with little work in windowwashing. i went to t
Lijang
Hej alle Nu har vi krt 18 timer i nattog og vi blev nsten inde i vores firemandskupe i alle de 18 timer. Vores aftensmad var kopnudler og vores morgenmad var en rigtig drlig bolle chips og nogle oreos kager som vi ogs spiste i kupen. I toget var der fire klasser der var hrde sder bld sder hrde senge og blde senge vi var p blde senge. Vi var ogs inde og se der hvor det var lige
logistics
So coming home and seeing people i realize how beyond comprehension the logistics of this experience are. How does Peace Corps work where are you who do you live with how do you live what do you do for money how do you have internet how many volunteers do you live withI figure id write a blog just explaining how this whole thing works. So Vanuatu is a country of 85 inhabited islands. th
The Cold Rockies
Since Russ and I separated after we saw his parent in Las Vegas I travelled north to Seattle. Managed to finally do washing and see the sights of Seattle in about 4 hours. Not much to do so got the bus up to Vancouver. I spent a week with my Dad's brother and his wife who looked after me well. Spent time downtown shoping for jumpers as its cold there No longer 30 degrees more like 15 with rain
Learning a little more about Chinese culture making friends making plans
Sorry that I am behind on my entries. I have had troubles with my internet at my apartment and needed to prepare my language a little bit before I could communicate what was wrong and fix it.The last few days have been great. The day before yesterday I met up with two Americans from IREE and went to get Indian food. It is the only legitimate foreign food I have found since being here actually run
Bequia June 3 2010
Greetings from Bequia.We made it through San Juan and St Vincent and onto Bequia with only a few hitches. San Juan was great. We had dinner at Cafe Puerto Rico right accross from Christopher Columbus square. Our waiter was very nice and come out to the square to take some pictures for us. Always tip your servers well and they will do anything for you. When we arrived at St Vincent the Cobbl
A few hours in Hong Kong
Pete took me to the airport for about 9pm as my flight out was at 11pm. I was all ready to check in when the airport lady told me she wouldn't check me in because my return flight was for more then 30 days in Thailand and I didn't have a visa. Long story short no one I asked could give me any answers regarding a visa because you get a 30 day visa upon arrival and can extend it when you are there
Accra Ghana.
June 2 I have finally made it to my destination Accra Ghana My flight was the first nonstop flight from Atlanta to Accra and there was a ceremony at the Atlanta airport before we took board. It was pretty cool to see the Ghanaians of Georgia there to celebrate this new direct flight. Now I am here many many hours later. We arrived at the airport which was much different than the usual airpo
Bringing Doctors to the Dying Patient’s Bedside – New York Times
![]() New York Times (blog) | Bringing Doctors to the Dying Patient's Bedside New York Times But the nurse gently reminded D. that it was winter break for the medical school and, like the other students, Dr. Alexander had gone home for vacation. ... Making Sure Patients Don't Die AloneNew York Times (blog) |
NFL medical heads and Goodell convene on brain injuries – CNN (blog)
NFL medical heads and Goodell convene on brain injuries CNN (blog) These “can lead to long-term consequences or later emergence of symptoms,” said Dr. Constantine Lyketsos, a doctor at Johns Hopkins University School of ... |
Another overhyped acupuncture study misinterpreted

Perhaps the most heavily studied of “alternative medicine” modalities is acupuncture. Although it’s hard to be sure as to the reason, I tend to speculate that part of the appeal to trying to do research in this area is because acupuncture is among the most popular of actual “alt-med” modalities, as opposed to science-based medical modalities co-opted by believers in alt-med and rebranded as “alternative” (diet and exercise, for instance, to which is all too often added the consumption of huge quantities of unproven nutritional supplments) or activities that make people feel better, whether they’re healthy or ill (massage, for instance). In contrast, acupuncture involves actually sticking needles into the skin. Never mind that the rationale for acupuncture, namely “redirecting” the flow of the “life energy” known as qi when it is blocked by sticking needles in “meridians” like some electrodes in some imaginary qi battery, is pure bunkum, as we’ve pointed out here at SBM time and time again. Somehow the image of needles sticking out of the skin, apparently painlessly and making some extreme acupuncture practices resemble Pinhead from the Hellraiser movie series, seems “sexy” as far as “alternative” therapies go, particularly since it’s “Eastern” as opposed to that reductionistically evil “Western medicine,” and, as we all know at SBM, “Western” is bad and “Eastern” is good.
So the fascination with acupuncture remains, so much so that an inordinate amount of research dollars are spent on studying it. Unfortunately, that money is largely wasted. As Steve Novella has pointed out, in general in medicine (at least these days), the trajectory of research is usually from bench research to animal models to small scale, less rigorous, pilot studies in humans to large scale, rigorously designed studies using many subjects. True, this order doesn’t always hold. For instance, if physicians make a compelling observation “at the bedside” of response to therapy or how a disease progresses, frequently, after making closer observations to confirm the initial observation, researchers will jump back to animal models and bench top research to try to figure out what’s going on. For such a progression to be useful, though, scientists have to be sure that the phenomenon in human patients under study actually exists.
Unfortunately, in acupuncture, the evidence is still unconvincing that there is any “there” there in that acupuncture effects appear to be no greater than placebo effects. As larger, more well designed studies using real placebo or sham acupuncture techniques, have increasingly shown that acupuncture does not function any better than placebo in human beings (and sometimes even worse), acupuncturists and acupuncture believers have been reversing the usual order of things, doing smaller studies and “pragmatic” (i.e., uncontrolled) clinical trials, where the placebo effect is not controlled for. Never mind that it doesn’t matter where the needles are placed (thus blowing the whole “meridian” idea out of the water) or even if the needles puncture the skin. Toothpicks work just as well as needles. Also never mind that the mythology of acupuncture as having been routinely practiced for over two thousand years (or, sometimes, four thousand years, is largely a creation of Chairman Mao, who elevated what was a marginal practice at the time to a modality that the state supported and promoted (1,2,3,4). Unfortunately, even the National Center for Complementary and Alternative Medicine (NCCAM) falls for this mythology.
Every so often, I’m amazed when an acupuncture study ends up in a high impact journal like Nature Neuroscience. Of course, when I read such articles, virtually inevitably I discover that what is being studied is not really “acupuncture” per se, but rather sticking needles into either people or animals. Sometimes, “electroacupuncture” (which is in reality not acupuncture at all, given that there was no source of electricity hundreds of years ago in China when acupuncture was supposedly invented) is misrepresented as acupuncture. Since a bunch of readers, both here and at my other blog, have deluged my mail box with this particular study, I felt obligated to have a look at it, even if Steve Novella has already weighed in with his excellent deconstruction. This particular study is especially annoying, because it’s been hyped to the nth degree, and even some news sources where the reporters should know better have fallen for it.
Before I get to the study itself, though, let’s take a look at the press release:
The research focuses on adenosine, a natural compound known for its role in regulating sleep, for its effects on the heart, and for its anti-inflammatory properties. But adenosine also acts as a natural painkiller, becoming active in the skin after an injury to inhibit nerve signals and ease pain in a way similar to lidocaine.
In the current study, scientists found that the chemical is also very active in deeper tissues affected by acupuncture. The Rochester researchers looked at the effects of acupuncture on the peripheral nervous system – the nerves in our body that aren’t part of the brain and spinal cord. The research complements a rich, established body of work showing that in the central nervous system, acupuncture creates signals that cause the brain to churn out natural pain-killing endorphins.
The new findings add to the scientific heft underlying acupuncture, said neuroscientist Maiken Nedergaard, M.D., D.M.Sc., who led the research. Her team is presenting the work this week at a scientific meeting, Purines 2010, in Barcelona, Spain.
“Acupuncture has been a mainstay of medical treatment in certain parts of the world for 4,000 years, but because it has not been understood completely, many people have remained skeptical,” said Nedergaard, co-director of the University’s Center for Translational Neuromedicine, where the research was conducted.
I’ll cut to the chase before proceeding with my usual infamously in depth and long-winded discussion of the study. Nedergaard’s study is interesting, but it really doesn’t show that “acupuncture works” any more than it really shows compelling evidence for a specific mechanism behind acupuncture. Unfortunately, as is commonly the case, much of the press reporting this study earns a big fat F for the spin being put on it. The Guardian, for instance, states:
The discovery challenges a widely held view among scientists that any benefit patients feel after having acupuncture is purely due to the placebo effect.
“The view that acupuncture does not have much benefit beyond the placebo effect has really hampered research into the technique,” said Maiken Nedergaard, a neuroscientist at the University of Rochester Medical Centre in New York, who led the study.
“Some people think any work in this area is junk research, but I think that’s wrong. I was really surprised at the arrogance of some of my colleagues. We can benefit from what has been learned over many thousands of years,” Nedergaard told the Guardian.
I love the “arrogance” gambit, don’t you? This time, it’s even coupled with the “appeal to ancient wisdom” fallacy. Nice. If you want to irritate me, pull the “arrogance” gambit and then couple it with appeals to ancient wisdom. After all, physicians from ancient civilizations were heavily into bleeding and purging, not to mention treating with toxic heavy metals. Go back to the ancient Egyptians, and you’ll see that praying and believing that the gods were responsible for diseases, with physicians and priests often serving the same purpose, were the rule fo the day. Does that mean such treatments were “wise” or efficacious. Meanwhile The Daily Mail entitled its report Let’s get straight to the point, acupuncture DOES ease pain, and The Telegraph entitled its report Acupuncture does work as it stimulates a natural pain killer, scientists find, while The Raw Story exulted, Researchers prove acupuncture’s effectiveness in pain therapy and the Wall Street Journal opined How Acupuncture May Work: Adenosine is Key to Acupuncture’s Effectiveness. Perhaps the silliest and most credulous commentary on this study comes from Elizabeth Armstrong Moore on CNET, who even entitled her post Think Acupuncture’s a hoax? Think again (Scientific research shows natural healing compounds), where Moore represented herself as a “skeptic” being “converted” to believing that acupuncture works, while Ars Technica writer Yun Xie laps this story up credulously. Even what I would normally consider more scientifically rigorous sources were not immune to the woo. For example, ScienceNow entitled its article on the study How Acupuncture Pierces Chronic Pain; The New Scientist’s blog Short Sharp Science, How acupuncture eases pain – maybe (which, despite the slightly skeptical title, was pretty much completely accepting of the spin placed on the study); and Nature’s blog The Great Beyond, Acupuncture ‘works in mice’.
So, with all this hype going on, even during a holiday weekend in the U.S. and the U.K., what does this overhyped study actually show? Are the headlines of “acupuncture works” and “scientists discover how acupuncture works” justified? Not so fast, there, pardner.
Perhaps the most infuriating aspect of all the hype is that the study being hyped actually describes a fair bit of interesting biochemistry behind the pain response. Unfortunately, what it doesn’t show is that “acupuncture works,” despite all the whining about “arrogance” from the study’s lead investigator. All it shows are two things: (1) that a chemical called adenosine is released when needles are stuck into the skin of mice and twisted and (2) that adenosine decreases the pain response. These are actually very interesting findings, albeit, as people I’ve corresponded with have pointed out to me, nothing new at all. Contrary to the way these results are being spun, they in now way validate the belief system behind acupuncture or show that “acupuncture works.”
Let’s get to the science in more detail, although I hate to do it by pointing out the Weekly Waluation of the Weasel Words of Woo-worthy credulous and annoying opening paragraph of the paper that reviewers should have shot down in flames but didn’t:
Acupuncture is a procedure in which fine needles are inserted into an individual at discrete points and then manipulated, with the intent of relieving pain. Since its development in China around 2,000 B.C., acupuncture has become worldwide in its practice. Although Western medicine has treated acupuncture with considerable skepticism, a broader worldwide population has granted it acceptance. For instance, the World Health Organization endorses acupuncture for at least two dozen conditions and the US National Institutes of Health issued a consensus statement proposing acupuncture as a therapeutic intervention for complementary medicine. Perhaps most tellingly, the U.S. Internal Revenue Service approved acupuncture as a deductible medical expense in 1973.
This is yet another example of an appeal to ancient wisdom, but this time it’s coupled with argumentum ad populum, better known as the appeal to popularity. I never thought I’d see the introduction to a scientific article appeal to, much less mention, the fact that the IRS allows a modality to be a deductible medical expense, but here it is. Where the hell were the reviewers? I could equally point out that the IRS allows medical deductions for the services of Christian Science prayer healers. Does that mean that Christian Science prayer is an effective treatment for anything? No, it does not. Add to that the whole false dichotomy between “Western” and “Eastern” medicine (yes, I know I mentioned it at the beginning of this post), a particularly odious and borderline racist construct in which the mythical “East” is represented as more “wholistic” and “spiritual” compared to the “reductionistic” and scientific brand of medicine. True, in the second paragraph, Nedergaard does mention the possibility of the release of opiod receptors, but there is zero discussion of the evidence for and against acupuncture, not even much of an acknowledgment other than that nasty “Western medicine” being so nastily “skeptical” of the practice, as though that were a bad thing.
The model used by Nedergaard is a model of inflammation that involves injecting complete Freund’s adjuvant (CFA) into the mice’s paws. As a result, the mice’s paws would become inflamed by the irritant properties of the CFA and thus more sensitive to innocuous stimuli, with a decreased latency period for withdrawal to painful or innocuous stimuli; in other words, the mice’s paws would be more sensitive, and the mice would react more strongly and rapidly to the stimuli of heat or touching. This sensitivity peaked at day four or five and then decreased. As a preliminary experiment, the investigators noted that, after the insertion of acupuncture needles into the mouse limb at the “Zusanli point,” which is located near the knee a microdialysis probe inserted less than a millimeter away registered a spike in extracellular adenosine levels, as well as ATP (which is broken down to adenosine outside of the cells), ADP, and AMP, that peaked at around 30 minutes.
Having established that adenosine was increased within 30 minutes of an acupuncture stimulus, Nedergaard then injected an chemical that binds to the cell receptor activated by adenosine, the A1 receptor agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA). Injecting CCPA into the Zusanli point greatly improved touch sensitivity and in essence reversed the increased sensitivity to heat. So far, so good. Apparently in the mouse adenosine has a lot to do with modulating pain response in peripheral nerves, and apparently a fair number of pharmaceutical companies are interested in developing adenosine agonists to take advantage of this effect in humans. Even better, this effect was not observed in mice genetically engineered not to make the adenosine A1 receptor, known as A1 receptor knockout mice, strong evidence that it was the A1 receptor that was responsible for the observed blunting of the pain response. Investigators also tested CCPA in a model of neuropathic pain (pain due to nerve dysfunction) and found it worked as well as it did in their model of inflammatory pain.
So what’s the link to acupuncture? Actually, that’s what I was wondering myself. Up until now, this paper was a fairly straightforward neuroscience paper looking at some interesting results. However, I doubt this paper would have gotten into Nature Neuroscience if all the investigators did was to show that a bit of local inflammation resulted in the secretion of adenosine into the extracellular fluid and then showed that that adenosine blunted the pain response in nearby nerve endings. That would have been much less interesting, because there is already a fair amount of literature implicating the A1 receptor as a target for the relief of neuropathic pain. But add the acupuncture to it, and you sex it up and get a paper into a high impact journal, which is apparently what happened here.
The unfortunate “bait and switch” of this paper is that it failed to mention that the Zusanli acupuncture point that the investigators used, apparently to the exclusion of all others, is not actually a leg or a pain acupuncture point. Although it is located on the leg, just inferior and lateral to the knee, the Zusanli point is described among traditional Chinese medicine (TCM) practitioners as the leg portion of the stomach meridian. According to TCM, this point is also known as Stomach-36 and its current indications are:
The current standard indications for zusanli, as reviewed in Advanced Textbook of Traditional Chinese Medicine and Pharmacology (21) are: stomach ache, abdominal distention, vomiting, diarrhea, dysentery, indigestion, appendicitis, flaccidity and numbness of the lower limbs, edema, mastitis, mania, epilepsy, cough, vertigo, palpitation, and emaciation due to consumptive disease. This latter indication corresponds to the concept that needling this point can tonify the sea of qi and thereby help to stop the wasting disease and restore ones body weight and vitality.
To illustrate the uniformity of indications amongst the Chinese authorities, the following were listed in Chinese Acupuncture and Moxibustion (22, 23), with slight differences on translation between the original Chinese and later Western publications: gastric pain, hiccup, abdominal distention, vomiting, diarrhea, dysentery, emaciation due to general deficiency, constipation, mastitis, intestinal abscess (acute appendicitis), numbness (motor impairment) and pain of the lower extremities, edema (beriberi), manic depressive psychosis.
Thus, according to acupuncturists, most associated with stomach and abdominal problems far more than lower extremity pain. Strange that the investigators didn’t mention that. I must say, though, it’s such a multipurpose acupuncture point, that I suppose I can’t harp on the investigators too much for using it for this indication, although I can’t help but note that the point seems mighty close on the mouse to where the sciatic nerve divides in the leg.
Be that as it may, here’s a concise summary of what the investigators found:
- In normal mice of adenosine, acupuncture reduced discomfort by two-thirds.
- In A1 receptor knockout mice, acupuncture had no effect on the reactions of the mice to the stimuli of touch or heat.
- During and after an acupuncture treatment, adenosine levels in the tissues near the needles was 24 times greater than before the treatment.
- Deoxycoformycin, a drug that inhibits the removal of adenosine by the tissues, increased the length of time that the adenosine remained in the tissues (surprise! surprise! given its known mechanism of action) but also appeared to increase the length of time that acupuncture treatment was effective.
- In mice who had acupuncture but in which the needle wasn’t rotated every five mintues, acupuncture had no effect.
So what does this all mean? First of all, this study is actually interesting for its implications for adenosine as a mediator of both inflammatory and neuropathic pain. I can’t fault its methodology, at least as far as it implicates the adenosine A1 receptor as a mediator of neuropathic and inflammatory pain in the lower extremity. It’s pretty clear in supporting the conclusion that mimicking the action of adenosine or somehow increasing its local concentration around a nerve might be a good strategy for relieving pain in humans. But do the results of this study actually support the efficacy of acupuncture, as Nedergaard claims?
Not so fast, there again, pardner.
This study actually says very little about acupuncture. What this study shows is that sticking needles in mice causes adenosine production and that that adenosine can blunt the pain response in nerves by binding to the A1 receptor. Nothing more. That’s all well and good, but it doesn’t validate acupuncture. The only thing in common with acupuncture in this study is the needle sticking part, and the investigators might as well conclude that this study validates ear piercing for pain relief. (Egads! Battlefield acupuncture strikes back!) So, it’s quite possible that needles twisted in the area near a nerve might release a flood of adenosine that might bind to A1 receptors in nearby neurons and blunt the pain sensation. No “meridians” or qi is needed to explain that. Moreover, this study notwithstanding, Nedergaard seems at a loss to explain how her results might be reconciled with numerous studies in humans that show clearly that (1) it does not matter where you stick the needles and (2) it doesn’t even matter if the needles are stuck through the skin. As I’ve pointed out before, just twisting the end of a toothpick against the skin produces the same effect as acupuncture. She does, however, give it the old college try to explain this result, although she does so using the hated term “allopathic” to describe “Western” medicine:
One may speculate that other non-allopathic treatments of chronic pain, such as chiropractic manipulations and massage, modalities that involve the mechanical manipulation of joints and muscles, might also be associated with an efflux of cytosolic ATP that is sufficient to elevate extracellular adenosine. As in acupuncture, adenosine may accumulate during these treatments and dampen pain in part by the activation of A1 receptors on sensory afferents of ascending nerve tracks. Notably, needle penetration has been reported to not confer an analgesic advantage over nonpenetrating (placebo) needle application, as opposed to our observations (Supplementary Figs. 2 and 3) 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, and acupoints may better overlap with their proximity to ascending nerve tracks than to the density of cutaneous afferents.
This is pure speculation without any compelling evidence, no more convincing than saying that rubbing a boo-boo makes it feel better, which is in essence what she’s saying. Worse, her speculations would also have been easy enough to test, given that she had the experimental model up and apparently running smoothly. Contrary to her implication, Supplemental Figures 2 and 3 do not refute the results showing that non-penetrating acupuncture works as well as penetrating acupuncture. In Figure S2, all that is shown is that using acupuncture at the Zusanli point on the contralateral leg doesn’t affect the reaction of ipsilateral leg receiving the acupuncture. All Figure S3 shows is that failing to rotate the needle results in loss of the analgesic effect. Neither refute findings in humans that non-penetrating acupuncture “works” just as well as penetrating acupuncture, where the needles are inserted to the “correct” points. Absent evidence from the current study showing that stimulating the skin results in the release of adenosine and subsequent blunting of the pain response in the extremities of these mice, Nedergaard would have been better off leaving this entire paragraph out of the paper. Moreover, contrary to the claim that “merdians” map to ascending nerve tracts is stretching it a bit, if you look at these maps. For instance, the kidney, stomach, and spleen acupuncture points line up somewhat with nerves at certain points in the body but are nowhere near ascending nerves in other parts.
Finally, there are two remaining huge problems with this paper. Here’s the second biggest first. Mice are much, much smaller than humans. The Zusanli point in a mouse is going to be within a couple of millimeters of the sciatic nerve or one of its major branches. In the human, it’s going to be at least a couple of centimeters away, possibly considerably further. In the mouse, the size of the needle relative to the size of the leg and distance from the sciatic nerve, as well as the nerve’s branches, the tibial and peroneal nerves, is going to be very close. The tissue damage, virtually no matter where the needle is stuck, is going to be close to these nerves. In humans, this is unlikely to be the case, particularly since the nerves are much further beneath the skin than they are in mice; that is, unless we want to start scaling things up and sticking nails into people’s knees. Thus, there is no good reason to think that these results will be unlikely to translate easily to humans.
What really bugs me about this article, though, is that it’s actually pretty cool science, for the most part. It’s not as new as I thought it was before some of my readers corresponded with me and I did a few PubMed searches, but in general its conclusions about the role of the A1 receptor and local adenosine release in response to tissue trauma seem sound. These guys have found something that may even have a potential clinical application. For instance, they found that local injection of A1 receptor agonists works the same as the “acupuncture” and that adding compounds that slow the removal of adenosine from the tissues improves the efficacy of the adenosine released into the tissues by minor trauma. Scientists can work with that. Scientists could take these observations and use them as the scientific justification to work on better, more specific, and longer acting A1 agonists. Perhaps they could even develop oral drugs that are broken down into adenosine or A1 receptor agonists in the peripheral tissues. If this paper’s conclusions regarding the importance of adenosine in pain signaling are correct, these would represent stragies that could very well work and very well improve pain control. One could even envision implantable pellets that could be placed in wounds or near relevant nerves to release A1 receptor agonists right where they’re needed over a long period of time.
Unfortunately, Nedergaard and her team are too enamored of the woo that is acupuncture to emphasize the true significance and potential usefulness of their findings. Worse, they were rewarded for their infatuation with acupuncture with not just a paper in a high impact neuroscience journal but with all sorts of publicity around the world. Instead of working to turn these observations into usable therapies, now Nedergaard and her collaborators will likely use their preliminary data to apply to NCCAM for a grant to study adenosine in acupuncture further, rather than pursuing this observation in a manner far more likely to lead to a clinical benefit in human beings. So much the pity. Woo poisons the real science it touches.
Finally, when you see aficionados of acupuncture cite this paper as “evidence” that acupuncture “works,” remember this: This study says absolutely nothing at all about all the other myriad claimed benefits of acupuncture in fertility treatments, headache, or hot flashes after menopause, to name a few. Sadly, it doesn’t even say that much about the use of acupuncture for chronic pain.
REFERENCE:
Goldman, N., Chen, M., Fujita, T., Xu, Q., Peng, W., Liu, W., Jensen, T., Pei, Y., Wang, F., Han, X., Chen, J., Schnermann, J., Takano, T., Bekar, L., Tieu, K., & Nedergaard, M. (2010). Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture Nature Neuroscience DOI: 10.1038/nn.2562
OTHER COMMENTARY:
- Acupuncture Works, Say Scientists
- A biological basis for acupuncture, or more evidence for a placebo effect?. (In this post, Ed Yong notes that one of the coauthors of this paper, Jurgen Schnermann, is married to Dr. Josephine Briggs. Dr. Briggs is the director of the National Center for Complementary and Alternative Medicine.
- Why was a study on ‘acupuncture’ reported so badly?
Potential New Mechanism of Pain Relief Discovered
The development of drugs and other treatments for specific symptoms or conditions relies heavily on either serendipity (the chance finding of a beneficial effect) or on an understanding of underlying mechanisms. In pain, for example, there are limited ways in which we can block pain signals – such as activating opiate receptors or inhibiting prostaglandins. There are only so many ways in which you can interact with these systems. The discovery of a novel mechanism of modulating pain is therefore most welcome, and has the potential of leading to entirely new treatments that may have better side-effect profiles than existing treatments and also have additive clinical effects.
A recent study by Nana Goldman et. al., published in Nature Neuroscience, adds to our understanding of pain relief by identifying the role of adenosine in reducing pain activity in the peripheral nervous system. The researchers, in a nice series of experiments, demonstrated that producing a local painful stimulus in mice causes the local release of ATP (adenosine triphosphate) that peaks at about 30 minutes. This correlates with a decreased pain response in the mice. Further, if drugs are given that prolong the effect of adenosine, the analgesic effect itself is prolonged.
Also, if drugs are given that activate the adenosine A1 receptor, the observed analgesic effect is replicated. When these experiments are replicated in knockout mice that do not have the gene for the adenosine A1 receptor, there is no observed analgesic effect.
Together these experiments are fairly solid evidence that local pain results in the local release of adenosine that in turn binds to the adenosine A1 receptor inhibiting the pain response. This is potentially very exciting – it should lead to further investigation of the adenosine A1 receptor and the effects of activating and inhibiting it. This may lead to the development of drugs or other interventions that activate these receptors and may ultimately be a very useful addition to our ability to treat acute and chronic pain.
Now Comes the Spin
In a rational science-based world, the above would be the end of this blog entry. But that is not the world we currently live in. In this study, the chosen method of provoking pain was the insertion of an acupuncture needle into the “Zusanli point” of the lower extremity and rotating it. This allowed the authors of this study to spin the results as if they were validation for acupuncture itself – and the mainstream press dutifully followed suit.
The introduction to this study is an apology for acupuncture itself, and sets the tone for the rest of the paper as well as the press release and comments to follow:
Acupuncture is a procedure in which fine needles are inserted into an individual at discrete points and then manipulated, with the intent of relieving pain. Since its development in China around 2,000 B.C., acupuncture has become worldwide in its practice. Although Western medicine has treated acupuncture with considerable skepticism, a broader worldwide population has granted it acceptance. For instance, the World Health Organization endorses acupuncture for at least two dozen conditions and the US National Institutes of Health issued a consensus statement proposing acupuncture as a therapeutic intervention for complementary medicine. Perhaps most tellingly, the U.S. Internal Revenue Service approved acupuncture as a deductible medical expense in 1973.
That this paragraph appears in a high-impact peer-reviewed journal is very curious (to put it mildly). It is full of misinformation and logical fallacies. Acupuncture is used for more than pain relief, and so making statements about the efficacy of “acupuncture” go way beyond the scope of this study, which involves only pain. The authors should have specifically pointed out that this study cannot be used to explain any indication for acupuncture that does not involve local pain relief. Acupuncture as it was practiced in China 4,000 years ago bears little resemblance to what is practiced today, and may have been more of a form a bloodletting.
The authors then make a false dichotomy between “Western medicine” and, presumably, “Eastern medicine” – which is an anti-scientific and culturally bigoted point of view. This is followed by an argument from popularity, and a particularly bizarre argument from authority – noting that the IRS accepts acupuncture as a medical expense. I was unaware that the IRS is a scientific medical organization.
The authors also fail to put this study into its proper context by reviewing existing evidence – the more traditional use of the introduction to peer-reviewed research. The clinical research on acupuncture, which is quite extensive, finds that any measured symptomatic effect is almost certainly due mostly or entirely to placebo effects. Further, it does not matter where you stick the acupuncture needle, nor even if you do not stick the needle through the skin. Twisting toothpicks against the skin in random locations has the same effect.
My interpretation of the research is that acupuncture (placing needles at specific acupuncture points to manipulate chi) does not work. There may, however, be non-specific physiological responses to the mechanical stimulation of sticking needles at random locations, or just poking toothpicks. This study, if anything, supports this interpretation – it, in fact, has identified a local mechanism of analgesia that can help explain a non-specific response to acupuncture, sham acupuncture, or placebo acupuncture and therefore is consistent with the clinical evidence showing no difference among these interventions.
This is also not the first study to identify potential local mechanisms of pain relief from mechanical stimulation. A 2002 study correlated insertional activity (depolarization of muscle fibers in response to needle insertion) or electrical stimulation with pain relief. This would explain why, in this study, constant twisting of the needle was needed to provoke pain relief – perhaps insertional muscle activity is needed to release adenosine, or increases its release.
By focusing on what is really going on here we can best understand how to develop methods to capitalize on these local mechanisms optimally for pain relief. It must be noted, however, that needle insertion gives very unimpressive results in clinical trials. It may be that the effect is too temporary to be worthwhile, at least as mechanically provoked – pharmacologically activating the adenosine A1 receptor may be a better strategy. Also, it is very difficult to extrapolate from mouse data as the subjects are much smaller than humans, and therefore their nerves and motor end-plates (the locations where the nerves innervate the muscles) are much closer together and superficial – closer to the skin.
Mechanisms are interesting, but net clinical outcomes in humans are the only kind of scientific data that really tells us if a modality works or not.
Conclusion
Finally, it has to be emphasized that this study says nothing about acupuncture itself, except for providing a possible mechanism for a non-specific local response. The term “acupuncture,” in fact, is becoming increasingly problematic and is confusing the scientific literature, not to mention the public. What is acupuncture? If we use the term broadly enough to mean any use of needles, with or without electrical stimulation, at any points, with or without skin penetration, etc. then the term is too broad to be useful. If we use the term narrowly – to mean sticking needles to a certain depth in specific acupuncture points that work through a novel mechanism specific to those locations, then we can say, based upon extensive research, that “acupuncture” does not work and its proposed underlying mechanisms are nothing more than pre-scientific superstition.
This study is an excellent example of the mischief caused by confusing the non-specific use of the term “acupuncture” with its more traditional use. Research involving acupuncture in its vaguest sense is used to promote “acupuncture” in the traditional sense. This is highly deceptive and scientifically sloppy.
The researchers of this current study could have used other controls to see if the effect they discovered is in any way specific to any acupuncture variables. For example – they could have used a non-acupuncture point as a control, or other forms of mechanical pain production that do not involve needles. I suspect any local pain production or mechanical trauma beyond a certain threshold would result in the same adenosine response – which certainly seems like a non-specific mechanism to modulate pain.
Because the authors did not do this, they did not actually research “acupuncture”. The description of this research in the published paper and in the press should have been as I discussed in the opening of this post. Instead, genuinely interesting research that may lead to novel pain treatments is being diverted as propaganda for an ancient superstition.
UNIX Sysadmin Boot Camp: Your Logs and You
We’re a few exercises into UNIX Sysadmin Boot Camp, and if you’re keeping up, you’ve learned about SSH and bash. In those sessions, our focus was to tell the server what we wanted it to do. In this session, we’re going to look at the logs of what the server has done.
Logs are like an overbearing mother who sneakily follows her teenage son around and writes down the addresses of each house he visits. When he realizes he lost a really important piece of baseball history at one of those houses, he’ll be glad he has that list so he can go desperately search for the soon-to-be-noticed missing bat. Ahem.
MAKE BEST FRIENDS WITH THIS DIRECTORY: /var/log/
When something goes wrong – when there’s hitch in the flux capacitor or too many gigawatts in the main reactor – your logs will be there to let you know what’s going on, and you can pinpoint the error with educated vengeance. So treat your logs with respect.
One of the best places to start harnessing this logged goodness is /var/log/messages. This log file reports all general errors with network and media, among other things. As you add to and learn your server’s command line environment, you’ll see specific logs for applications as well, so it’s a very good idea to keep a keen eye on these. They just might save your life … or server.
Some of the most commonly used logs (may vary with different Linux distributions):
/var/log/message– General message- and system-related info/var/log/cron.log– Cron job logs/var/log/maillog– Mail server logs/var/log/kern.log– Kernel logs/var/log/httpd/– Apache access and error logs/var/log/boot.log– System boot logs/var/log/mysqld.log– MySQL database server logs/var/log/secure– SSH authentication logs/var/log/auth.log– Authentication logs/var/log/qmail/– Qmail log directory (more files inside this directory)/var/log/utmpor/var/log/wtmp– Login records file/var/log/yum.log– Yum log files
There are plenty more in-depth logs – particularly involving raw system components – and others that act similarly to logs but are a bit more active like tcpdumps. Those are a little more advanced to interpret, so I’ll save them for another guide and another day.
At this point in our UNIX workout series, you’re familiar with the command line, you know the basics of how to tell your server what to do and you just learned how to let the server tell you what it’s done. There’s still a bit of work to be done before you can call yourself a UNIX ninja, but you’re well on your way. In our next installment, we’re going to take a step back and talk about p455w0rd5.
Keep learning.
-Ryan
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Application Services and APIs
There’s an old saying that what’s down in the well comes out in the water. It just means that if the inside of something is good, then the outside will also be good and vice versa. That’s true for a web portal as well. If the machinery and systems behind the portal aren’t strong, then the portal will never be great. After all, a portal is just a window into the systems behind the curtain. The functionality and design of the portal are limited by the information it can access and the automated services it can utilize.
Let’s bring this back to The Planet: What does Orbit have access to? A lot. The Planet has spent years automating systems and refining our databases. We now have quite a collection of automated services and a strong data warehouse. Our current Orbit 2.0 platform offers a lot of automated functionality. With the iPhone web app, you can easily access the key functionality and data on your phone.
We’re working on a new way to leverage all of that automation and information. As we started looking at how we can take our portal to the next level, we took a long look at our software architecture and infrastructure. What we found was some great functionality built on a sort of mish-mash of technologies and architectures. This isn’t uncommon in systems that are 10 years old, but it definitely makes the job of upgrading the portal more time consuming.
We have started implementing a Services Oriented Architecture (SOA) from the ground up. This will provide us with a great foundation for an extensible internal API, as well as a robust external API. But first, we have a lot of work in front of us to untangle and normalize internal services and functional responsibilities. We are prioritizing that work according to the results of customer surveys and visits. All of this will result in more dependable portal functions and a much more powerful API.
What you will see is a pipeline of functionality: New internal services will be followed by portal improvements, which will be followed by new APIs.
SOA Services (Internal) » Portal Improvements » External APIs
Right now, we are in beta on some new RESTful APIs. We want to prove out our infrastructure and approach. Our SOA rollout and beta should be happening around the end of Q2/early Q3.
We’re working in a lot of directions at once right now. In my next blog, I’ll talk about the changes we’re making in all of our areas that will provide the foundation for this new and improved collection of services and APIs.
-Duke
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Concussion doctor: NFL needs "an enormous culture change" – ProFootballTalk
Concussion doctor: NFL needs "an enormous culture change" ProFootballTalk ... has given Ellenbogen and Dr. Hunt Batjer complete freedom to operate the committee the way they believe is best, based on their expert medical opinions. ... |
Outrageous Developments as U.S. Government Works With BP Criminals
According to Mike Pappantonio, who appeared on the Thom Hartmann radio show today, June 2nd, said the workers in the Gulf of Mexico are getting seriously ill due to the use of dispersants. BP does not want to admit it, but scientists and the MSDS fact sheet on Corexit (material safety data sheet) said that the use of Corexit can cause a person to suffer from “incurable flu-like” symptoms, including diffused muscle pain, nosebleeds and breathing problems. The MSDS says people who work with Corexit need respirators because being around it can lead to organ damage, especially of the kidneys, liver and lungs. BP is playing down the bad effects of their dispersant, but Corexit can cause very serious health effects in people besides organ damage, including altering a person’s DNA. This is according to Mike Pappantonio, the MSDS sheet for Corexit, and Dr. Ricki Ott, who worked on the Exxon Valdez spill aftermath. BP has been firing people who even brought in their own respirators because they didn’t like the way it looked. From EDF:
Writing in the Huffington Post, Dr. Riki Ott, a marine toxicologist who worked on environmental remediation after the Exxon Valdez oil spill, noted that some of the first responders to the Deepwater Horizon disaster “are getting sick from…working on the cleanup”. Boom installers and other temporary workers have complained of nausea and bad headaches (conditions that might be linked with overexposure to 2-butoxyethanol, a major component of one of the COREXIT chemicals).
Mike Pappantonio also confirmed that President Obama (via the Secretary of Labor) has suspended the Davis-Bacon act and now BP is importing workers from Mexico to work on the clean up with inadequate safety gear and paying them slave wages. This is something George Bush did after Hurricane Katrina and he was highly criticized for it. It basically means that people can be hired by BP and work for less than minimum wage, and BP has no legal safety responsibilities towards people that come from other countries and work in the U.S.
Streaks left by oil that retreated during low tide are visible on a public beach on June 2, 2010, in Dauphin Island, Ala. (Win McNamee/Getty Images)
And here are some Dick Cheney ties to this mess from Pro Publica:
“In a speech last week on the disaster unfolding in the Gulf, President Obama told the nation that for decades, there existed a “scandalously close relationship between oil companies and the agency that regulates them,” and that he took responsibility for a culture that had “not fully changed” under his administration.
On that subject—the culture of coziness between the Minerals Management Service and industry—a non-profit Wyoming news service WyoFile published a report today that details some of the ties between MMS internal culture, the state of Wyoming, and the state’s native son, Dick Cheney. From WyoFile:
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Renowned Sculpture Artist Louise Bourgeois Dies
Louise Bourgeois, the grande dame of contemporary artists best known for her sculpture and disquieting symbolism, died Monday of a heart attack at a hospital in Manhattan. She was 98.
Sculpture became Ms. Bourgeois’ primary medium after 1945 when the Peridot Gallery, a prestigious venue in Manhattan’s then-intimate art world, staged her first solo sculpture show. In 1982, Ms. Bourgeois became the first female artist to be honored with a retrospective at the Museum of Modern Art. Subsequent retrospectives in 1993 and 2007 that visited major institutions in New York, Washington, Los Angeles, Madrid, London, Paris and St. Petersburg, Russia, consolidated her position as a world figure in art.
Her work, which is on view at Gallery Paule Anglim in San Francisco through June 12, came to the attention to the Bay Area public in 2007 when the San Francisco Arts Commission installed her giant bronze “Crouching Spider” (2003) at Pier 14 on the Embarcadero. It stayed until early 2009. In 1996, the Berkeley Art Museum presented a career survey of Ms. Bourgeois’ drawings.
Ms. Bourgeois acknowledged that the spider imagery in her art was a Freudian symbol of female sexuality, a private symbol of her mother and a celebration of arachnids’ crucial predator role in keeping the Earth’s insect population in check.
She frequently said her work sprang from conscious and unconscious memories of her childhood, with a caring but invalid mother and an imperious, unfaithful father.
In the mid-’60s, a rising generation of feminist artists and critics rediscovered her art, and although she was never entirely comfortable with that affiliation, it accelerated a career that previously had been in low gear.
Born in Paris on Dec. 25, 1911, Ms. Bourgeois worked early on for her parents, who marketed and restored antique tapestries. Some of her art’s spider imagery also evokes her youthful part in repairing threadbare textiles.
Although Ms. Bourgeois drew frequently to assist in the family business, she studied mathematics when she entered the Sorbonne, in search, she said, of impersonal, unbreakable rules.
She soon digressed into art studies at various schools in Paris and a stint as studio assistant to Fernand Leger (1881-1955), one of France’s most esteemed painters at the time.
In 1938, Ms. Bourgeois married American art historian Robert Goldwater (1907-1973), a specialist in tribal arts who wrote extensively about their influence on European modernism.
Once settled in New York, where she continued her studies at the Art Students League, Ms. Bourgeois entered the widening circle of European artists who sought refuge there from the war, including several Surrealists, whose influence she would later deny, though critics continue to make that connection.
In 1993 Ms. Bourgeois represented the United States at the Venice Biennale and London’s Tate Modern commissioned for its 2000 opening a suite of works from her for its mammoth Turbine Hall.
Ms. Bourgeois received several honorary doctorates, and, in 1997, the National Medal of Arts. France named her an Officer of the Order of Arts and Letters and conferred its Grand Prix National de Sculpture in 1991.
She is survived by sons Jean-Louis and Alain, both of New York City, two grandchildren and one great grandchild. A third son, Michel, died a decade ago.
Various Works by Edward Kinsella
These beautiful illustrations were created by contemporary artist and illustrator Edward Kinsella. Edward was born in St. Louis, Missouri in 1983 and graduated from Ringling School of Art and Design in 2006, having also attended two summers of the Illustration Academy. He now lives and works in Chicago, Illinois.
To learn more about Edward Kinsella and view additional images, please visit the following links:
http://www.edwardkinsellaillustration.com – Edward Kinsella’s official website
edwardkinsellaiii.blogspot.com – Edward Kinsella’s official blog
Gallery Nucleus Presents Enchanté
FOR IMMEDIATE RELEASE
Gallery Nucleus Presents
Enchanté
June 19, 2010- July 12, 2010
Opening Reception: Saturday June 19, 2010 (7 pm – 11 pm)
Alhambra, CA – Gallery Nucleus is excited to present Enchanté, an exhibit featuring a mélange of contemporary French illustrators and fine artists.
Featured artists include those that have graced previous Nucleus exhibits: Adolie Day, Véronique Joffre, Véronique Meignaude, and Marguerite Sauvage, and artists exhibiting at the gallery for the first time: Benjamin Lacombe, Rebecca Dautremer, Gerald Guerlais, Lilidol, Emmanuelle Pioli and more. We are pleased to introduce a diverse flavor of France as told by its freshest creative voices.
Despite national roots that tie all these artists together, each has an aethetic that is uniquly their own. Exploring a range of subject matter with both personal and published pieces, their caliber of work welcomes closer inspection and appreciation. Artists like Alexandre Day who spins dramatic portraits out of ethereal and emotional lines, to the vintage styling of chaotic worlds and funky characters by McBess, the artists showing in Enchanté deliver an exhibition rich with artistry, charm, and passionate narratives.
Featured Artists:
Adolie Day
Alexandre Day
Benjamine Lacombe
Eric Gosselet
Gerald Guerlais
Lilidoll
Marguerite Sauvage
McBess
Véronique Joffre
Véronique Meignaude
Samuel Ribeyron
Sebastien Mesnard
Stephane Tartelin
Rebecca Dautremer
Simon Goinard
Contact:
Nucleus Studios, Inc
(626) 458-7477
Address: 210 East Main St Alhambra CA 91801
Store Hours: Fri-Sat (11am-10pm), Mon- Sun(12pm-8pm)
http://www.gallerynucleus.com


















