Acupuncture for Parkinson’s disease?

Critics who don’t like my insistence on applying the scientific method to the claims of alternative medicine sometimes accuse me of unrelenting hostility towards alternative medicine, as though no amount of evidence would ever convince me of the efficacy of various alternative medicine therapies. Nothing could be further from the truth; I merely insist, as I have from the very beginning, that, at the very least, the claims of alternative medicine should be subject to the same testing by the scientific method that “conventional” or “scientific” medical treatments (a.k.a. evidence-based medicine, or EBM for short) are before being adopted by physicians. In other words, I reject the very term “alternative medicine” as a false dichotomy between “standard” medicine and an “alternative.” To me it should all be just medicine.

Some alternative medical treatments (such as homeopathy, for example) are so obviously implausible scientifically that it doesn’t take much testing to be able to dismiss them as the bunk that they are. However, for others, the evidence is not so clear-cut, even when the scientific rationale may be a bit dubious. To me, acupuncture falls into this latter category. Certainly, the whole thing about qi (energy) and using needles to “unblock the flow of qi” by placing them through the skin along certain “meridians” is nothing but a lot of mystical hokum, and certainly these meridians are not based on any anatomic structures that we know of. Even so, it’s possible that acupuncturists may have stumbled on something, even if their rationale is full of crap, scientifically speaking. The lack of scientific rationale wouldn’t bother me so much if acupuncturists didn’t still insist on invoking qi as the reason for its alleged efficacy and downplaying the possibility of complications (for example, there are 81 articles in PubMed about pneumothorax as a complication of acupuncture and even reports of the occasional fatality). Still, it’s always possible that sticking needles in someone’s skin somehow releases endorphins or does something therapeutic, although it doesn’t seem to matter whether the needles are stuck along the “meridians” or not.

So what, then, am I to make of this study whose abstract follows below the fold?

Kang JM, Park HJ, Choi YG, Choe IH, Park JH, Kim YS, Lim S. Acupuncture inhibits microglial activation and inflammatory events in the MPTP-induced mouse model. Brain Res. 2007 Feb 2;1131(1):211-9.

Department of Meridian and Acupoints, College of Korean Medicine, Kyung Hee University, Seoul, South Korea; WHO Collaborating Centre for Traditional Medicine, East-West Medical Research Institute, Kyung Hee University, Seoul, South Korea.

Using a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD), this study investigated on the neuroprotective effects of acupuncture by examining whether acupuncture contributed to inhibiting microglial activation and inflammatory events. C57BL/6 mice were treated with MPTP (30 mg/kg, i.p.) for 5 consecutive days. Acupuncture was then applied to acupoints Yanglingquan (GB34) and Taichong (LR3) starting 2 h after the first MPTP administration and then at 48 h intervals until the mice were sacrificed for analyses at 1, 3, and 7 days after the last MPTP injection. These experiments demonstrated that acupuncture inhibited the decreased of the tyrosine hydroxylase (TH) immunoreactivity (IR) and generated a neuroprotective effects in the striatum (ST) and the substantia nigra (SN) on days 1, 3, and 7 post-MPTP injections. Acupuncture attenuated the increase of macrophage antigen complex-1 (MAC-1), a marker of microglial activation, at 1 and 3 days and reduced the increases in cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression on days 1, 3, and 7. In MPTP group, striatal dopamine (DA) was measured by 46% at 7 days, whereas DA in the acupuncture group was 78%. On the basis of these results, we suggest that acupuncture could be used as a neuroprotective intervention for the purpose of inhibiting microglial activation and inflammatory events in PD.

Basically, this study looked at a mouse model of Parkinson’s disease that results in similar clinical symptoms as sporadic Parkinson’s disease in humans. It is the loss of dopamine-producing neurons in a part of the brain called the substantia nigra that is responsible for the development of Parkinson’s disease, and at present treatment is based on trying to replenish the disappearing dopamine with a drug called L-dopa, which is converted into dopamine by these same neurons. Basically, the injection of a chemical (MPTP) mimics this condition in mice by causing inflammation and destruction of dopamine-producing neurons in the mouse brain.

What the investigators did was to divide the mice up into four groups: (1) control; (2) MPTP alone; (3) MPTP plus acupuncture at the Taichong (LR3) and Yanglingquan (GB34) acupoints (whatever they are); apparently they’re in the leg); (4) MPTP plus sham acupuncture in the hips. Mice were all treated identically, as far as I could tell, even up to having the groups of mice that didn’t get acupuncture restrained for 30 seconds, just as the mice who received acupuncture were. The methodology seems pretty good, at least in the overall experimental design. The results reported an attenuation of increases in substances associated with activation of inflammatory cells and a relative preservation of dopamine levels in the MPTP-treated mice also treated with acupuncture. It also seemed to be specific, because the sham acupuncture groups didn’t show the same apparently protective effect.

So, does this study mean that acupuncture would be useful in the treatment of Parkinson’s disease. Well, not so fast. Maybe it does; maybe it doesn’t. (More likely it doesn’t.) For one thing, some of the effects reported are rather small; and for at least one of them sham acupuncture appeared to have a similar, albeit weaker, protective effect. For another thing, the people looking at the immunohistochemical staining of the tissue slides of mouse brain were not blinded to which experimental group they were in. This is not nearly as much of a concern for the Western blots for protein measurements, mainly because they are not nearly as prone to observer effects, but blinding of the examiner to the experimental group is essential in the reading of any sort of tissue section staining because subtle, unintentional bias can creep in. For example, the tissue sections stained for an enzyme that is an important indicator of the presence and viability of these neurons, tyrosine hydroxylase (TH). Let’s say you’re counting the percentage of the neurons that stain positive for TH; if you know which tissue section belongs to which experimental group, it is very easy in the case of cells that stained weakly to let yourself read such cells as positive on tissue section swhere you expect to see more positive staining (the control and the MPTP plus acupuncture site) and as negative in tissue sections where you don’t (the MPTP alone and MPTP plus sham acupuncture groups). This is not dishonesty, nor is it usually intentional (although occasionally it can be). It is merely a subtle form of confirmation bias, and to guard against it is the very reason blinding to experimental groups is so important, not just in experiments like this but even more so in clinical trials. In any case, the staining didn’t show much, if any, difference in the substantia nigra. At least the tissue sections that the investigators decided to display didn’t show that impressive a difference, and we scientists know that investigators always pick their very best pictures to use in any paper. (Certainly, I always pick my best tissue sections and best blots to display in any paper.) There did appear to be a difference on Western blots of protein, but I’m always a little suspicious of quantifying Western blots because they can be notoriously nonlinear. However, this is no worse than many other papers that do similar sorts of measurements of protein levels; so I have to assume that the evidence does show a treatment effect due to acupuncture on the levels of the proteins examined.

Finally, and perhaps most importantly, I’d really like to see some clinically relevant observations in this animal model, the shortcomings of mouse models of disease notwithstanding. Unfortunately, the investigators never reported whether acupuncture alleviated the symptoms of this experimental model of Parkinson’s disease in their mice, something other researchers have tried to do in a rat model of Parkinson’s disease. Also, some of what was written in the paper also gives me pause. For example, the authors cite a really dubious case series claiming that acupuncture “possesses definite therapeutic effectiveness for Parkinson’s disease” in support of a contention that acupuncture can relieve symptoms of Parkinson’s disease and delay its progression in patients, while failing to cite a more recent double-blinded randomized pilot study that found no statistically significant improvement in their scores on the motor subscale of the Unified Parkinson’s Disease Rating Scale (UPDRS), the Parkinson’s Disease Questionnaire (PDQ-39), and the Geriatric Depression Scale.

Still, I realize that last complaint about the papers the authors chose to cite or not to cite is bordering on nit-picking. It doesn’t change the fact that we’re left with the results of this study, which may indicate a physiologic effect of acupuncture that appears independent of any sort of placebo, given that it’s in a mouse. (That’s all assuming that this result can be replicated by other laboratories, as replication of results like these is critical.) Even so, if you look at the totality of the evidence out there, it is mostly negative as far as demonstrating any likely therapeutic effect of acupuncture in Parkinson’s disease. This study doesn’t change that, and there are always outliers. Whether the results of the study discussed translate into benefits in human patients with Parkinson’s disease or not, there’s one thing we can say: If acupuncture has any therapeutic value at all in Parkinson’s disease (or any other disease or condition), it will be due to an objective, measurable mechanism that is decipherable by science. It will not be due to “altering the flow” of an undefined, unmeasurable “life energy” (qi).