A new acupuncture vs. placebo acupuncture study has been making headlines due to results of a study suggesting that there may be a difference in opioid receptor response in acupuncture vs. placebo acupuncture.

Several large-scale studies [1-3] have been released showing that acupuncture and various forms of placebo acupuncture have clinically insignificant differences in the reduction of pain, proponents of acupuncture are now looking at brain-imaging to explore the mechanisms of acupuncture and placebo acupuncture to determine if acupuncture and placebo acupuncture operate via different mechanisms.

In this study [4], researchers hypothesized that long term acupuncture therapy may result in increased opioid receptor availability and that these effects would not be observed in a placebo acupuncture group. Their subjects consisted of 20 women randomly divided into 2 groups of 10 subjects. One group received traditional acupuncture treatment while another group received non-invasive, placebo acupuncture. Results from PET scans using contrast material were taken during a 90-minute period, during which acupuncture treatment or sham acupuncture treatment was administered during the 45-90 minute timeframe. A period followed in which subjects received 7 acupuncture or sham acupuncture treatments, and then the PET scan procedure was repeated, for a total of 9 treatments. Results indicate acupuncture therapy evoked short-term increases in MOR binding potential, in multiple pain and sensory processing regions including the cingulate (dorsal and subgenual), insula, caudate, thalamus, and amygdala. Acupuncture therapy also evoked long-term increases in MOR binding potential in some of the same structures including the cingulate (dorsal and perigenual), caudate, and amygdala. These short- and long-term effects were absent in the sham group where small reductions were observed, an effect more consistent with previous placebo PET studies.

There are several pieces of information regarding this study that were left out of news headlines an abstracts, so I will attempt to summarize them here and then offer my own analysis of the results. However, it should be clear that I am not a neurologist, and thus my knowledge of neurology is somewhat limited.

Subjects were blinded to which treatment group they were in, and they were also asked to guess which treatment group they thought they were assigned to after the first PET scan. There was no significant difference between groups, and thus it can be assumed that the subjects remained adequately blinded, though the study does not mention any blinding of the researchers, making it quite likely that the researchers were unblinded, which could have an effect on the study results.

During the acupuncture treatment, needles were left in during PET scan acupuncture treatment measurement during the 45-90 minute timeframe, while no needles were retained during the sham acupuncture group given that no needle penetration occurred during sham acupuncture. Clearly then, PET scans during that 45-90 minute period involve one group receiving an active treatment (given that needles were in their skin) while the sham group received inactive treatment (given that no needles were present). It seems obvious to me that there will be neurobiological differences between a group of people being measured while needles are inserted into them and a group of people who do not have needles in them, so their results are not surprising. Additionally, even though subjects may have not know which group they were in (they had to have had no prior acupuncture experience to participate), they quite likely were aware of whether or not needles remained in place during the PET scans, especially given the fact that both treatment groups involved placement on the head and ear. This knowledge could provide an explanation for the differences in treatment groups and is not addressed in the study. As such, even though the subjects were ignorant of whether or not they were receiving placebo treatment or not, the same cannot be said of their ignorance of the presence of needles placed in their body during PET scans.

What I find especially interesting about this study is the discussion of opponents of acupuncture in the introduction. The researchers wrote:

"Recent controversy in the field of acupuncture research was generated when several large scale randomized controlled trials in chronic pain patients failed to show superiority of acupuncture over sham acupuncture methods. This has led opponents of acupuncture therapy to suggest that it is no more effective than a placebo intervention."

I fail to see why one needs to be an opponent of acupuncture therapy to suggest exactly what the large scale randomized controlled trials are suggesting - that acupuncture therapy is not superior to placebo intervention. This sentence seems to indicate potential bias on the part of the researchers in this study. The data from these studies are very clear.

If the clinical results between acupuncture and placebo acupuncture are the same, it seems to me that potential side-effects are far more important than the fact that acupuncture and placebo acupuncture potentially operate via different mechanisms. This difference in mechanisms is irrelevant, or at least far less relevant than clinical results or side effects. It could be argued that different types of placebo acupuncture have different neurochemical mechanisms of action as well, but thus far no study has documented these potential differences. This study is weak in that it only compares two different treatments. If the study had used acupuncture and two different types of placebo acupuncture that had already been established through trials to have similar clinical results, and then shown that the mechanism of action for the placebo acupuncture was the same while the acupuncture group had a different mechanism, then the results would be more convincing.

The researchers indicated that previous studies indicated that the neurobiological response to acupuncture was distinct from pain and sham acupuncture, but one of the articles [5] I read in support of this claim (there were three total, and all appeared to be from the same group of people as evidenced by common authors. I read the newest one.) failed to blind subjects to which treatment they were receiving and thus is poor evidence to support their claim. Instead, this seems to support evidence that there is a different neurobiological response in individuals who know they are receiving acupuncture or a placebo, which is to be expected.

Regardless, it seems fairly obvious to me that measuring neurobiological responses in a PET scan while some subjects have needles inserted during the scan and others do not is measuring a neurobiological response to needles being in the skin versus not in the skin.  Sticking needles in subjects would likely provoke a different neurochemical response in subjects when compared to placebo acupuncture, which involved no needle insertion. So, if you do two different physical things to people, this provokes different neurochemical responses. Didn't we already know this? At least this study does not argue that acupuncture and placebo acupuncture have different effects. Instead, it argues that acupuncture and placebo acupuncture have different mechanisms. My less than dignified response is, "So what?"

 

1. Brinkhaus B., Witt CM, Jena S, Linde K, Streng A, Wagenpfeil S, Irnich D, Walther HU, Melchart D, Willich SN. Acupuncture in patients with chronic low back pain: a randomized controlled trial. Arch. Intern. Med. 2006;166:450-457.

2. Linde K, Streng A, Jurgens S, Hoppe A, Brinkhaus B, Witt C, Wagenpfeil S, Pfaffenrath V, Hammes MG, Weidenhammer W, Willich SN, Melchart D. Acupuncture for patients with migraine: a randomized controlled trial. JAMA 2005;293:2118-2125.

3. Melchart D, Streng A, Hoppe A, Brinkhaus B, Witt C,Wagenpfeil S, Pfaffenrath V, Hammes M, Hummelsberger J, Irnich D, Weidenhammer W, Willich SN, Linde K. Acupuncture in patients with tension-type headache: randomized controlled trial. BMJ 2005;331:376-382.

4. Harris RE, Zubieta JK, Scott DJ, Napadow V, Gracely RH, Clauw DJ. Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on μ-opioid receptors (MORs) NeuroImage 2009;47:1077-1085

5. Napadow V, Kettner N, Liu J, Li M, Kwong KK, Vangel M, Makris N, Audette J, Hui KK. Hypothalamus and amygdala response to acupuncture stimuli in carpal tunnel syndrome. Pain 2007;130: 254-266.

 

Christina Stephens, OTD/s blogs at www.ziztur.com