The April 1 issue (-giggle-) of PLOS ONE published an article on the alternative medicine modality of electro-acupuncture (EA) by a group of investigators from Shanghai, China (DOI: 10.1371/journal.pone.0122087). The basic premises of the study are sound:

  • Certain types of brain tumors require radiation therapy or ‘radiotherapy’ as a treatment option; this therapy uses high-energy radiation beams to destroy the cancerous cells in a targeted manner.
  • However, even in case of successful tumor radiotherapy, some normal brain tissue may also be damaged.
  • Radiation-induced damage may result in a decline in cognitive functions, which severely reduces the quality of life in a certain percentage of long-term survivors.
  • The exact mechanism underlying radiation-induced cognitive decline is unclear, but likely includes decreased generation of neurons (brain cells) in certain brain regions, as well as inflammatory processes in the brain. It is known that management of brain inflammation can significantly stave off the cognitive impairment.

To formulate an alternative to existing treatments, the authors hypothesized that EA may be a useful modality to preserve the function of the brain after radiation-induced damage. Using a rat model, they irradiated the brain with high-energy X-rays (similar to what is used in human patients) and assessed the damage by examining various clinical parameters, such as (a) integrity of the blood-brain-barrier, (b) biochemical correlates of certain brain functions, as well as (c) certain functional tests for the rats. In their tests, EA appeared to protect the blood-brain-barrier, decrease chemical mediators of inflammation, and reduce functional deficit after brain irradiation.

Pretty neat, right? Well, except that the choice of treatment, EA, and the model tested both have several shortcomings peculiar to them, including a lack of prior plausibility, as I have mentioned elsewhere.

I had several methodological questions I wanted to ask the authors. I thought it best to put my questions in form of a comment after the article on PLOS ONE, since this Open Source journal offers post-publication review in form of reader comments. Following is the text of what I wrote:

This is an interesting study utilizing various techniques to demonstrate the claimed protective effect of electro-acupuncture after brain irradiation. The study is thorough and detailed, but I have some fundamental questions about the methodology used, including the appropriateness of controls. I hope the authors would clarify these questions.

  1. Given that classical acupuncture was developed – and acupuncture points mapped out – for humans, how appropriate is the use of the two acupoints on rats in this study? How were their precise locations determined for use, and where is the evidence that those acupoints on the rats are functionally equivalent to the described acupoints in humans?
  2. Given that electro-acupuncture (EA) as a modality was unknown in traditional Chinese medicine, how appropriate is its use as a substitute for standard acupuncture? Are the actions and effects of standard acupuncture and EA done at the same acupoints different from each other? Is there any evidence to that effect? Was this assessed for the purpose of this study?

I am sure the authors would agree that in such experiments, controls are very important to help dissociate a true signal from noise. For instance, the authors have shown that no acupuncture and EA subjects show very similar outcomes for all parameters tested, demonstrating that EA isn’t harmful to the subjects in terms of tested parameters, which is an important observation. However, when it comes to comparisons between irradiation and BI + EA, or between BI and the controls, I have a few more questions about the specificity of EA.

  1. Was there a control where the same amount of electricity was applied to the acupoints without using the acupuncture needles?
  2. Was there a control where the acupuncture needles were placed in acupoints different from the two used and electricity was applied?
  3. In human patients, when the acupuncture needles are inserted, they are often rotated until the patient expresses the sensation of warmth or mild pain/discomfort – which the acupuncturists define as ‘de qi’, taken to be indicative of the correct placement of the needle required for successful treatment. How is this assessed in a rat?

The results that the authors have presented appear to show undeniably that following EA, the levels of most variables tested have come down to the levels of naive controls, compared to the irradiated group. I would like to understand if this observed effect is specifically due to acupuncture, due to EA as a modality, or due to non-specific phenomenology associated with transdermal or transcutaneous electrical stimulation. I hope that the authors would oblige me and satisfy this scientific curiosity.

PLOS ONE requires commenters to declare competing interests so that the possibility of bias, even in comments, may be evaluated. I wrote: I am generally critical of complementary and alternative medicine modalities, including acupuncture, and do occasionally write critiques of published papers in this field in the form of blog posts. I would sincerely hope that my honest declaration would not hinder the elicitation of a response from the authors. I shall update this post once I hear back from them.