There's another trial that came out this year in Physical Medicine and Rehabilitation by Yao et al15 that studied the efficacy of acupuncture over sham for the treatment of carpal tunnel. It was found that both sham and true acupuncture were helpful in the treatment of carpal tunnel, but failed to demonstrate a statistically significant difference between the verum and sham acupuncture groups.
What is particularly interesting about this study is that the natural history of carpal tunnel suggests that you will notice a 20% to 40% improvement over time. However, this study showed an 88% statistically significant improvement in both the true and sham acupuncture groups, which was maintained over 3 months of follow-up after the treatments ended.
The question that arises now is how you reconcile all of this, because it seems that the first piece of information that you come up with is that the sham may actually be a different form of active treatment. There's an interesting study by Richard Harris and others in neuroimaging that was published in 2009.16 Harris' team looked at the effects of true and sham acupuncture on the mu-opioid receptors in the central nervous system (CNS) using positron emission tomographic scanning in patients with fibromyalgia. Prior studies in patients with fibromyalgia have demonstrated increased levels of endogenous opioids in the cervical spinal fluid with decreased sensitivity in the mu-opioid receptors in the CNS regions known to be associated with the modulation of pain.
In the Harris study, the authors found that true acupuncture therapy evoked both short- and long-term increases in mu-opioid-binding potential receptors in the multiple pain areas and sensory processing areas associated with pain regulation. This was associated with clinical reports of pain reduction on the part of the subjects.
In the sham group, they also reported reduction in pain, though less than that in the true acupuncture group, and the positron emission tomographic scan showed no effect on the sensitivity of the mu-opioid receptors. The binding potential of these receptors did not improve as they did with the acupuncture treatments.
We know from prior studies that both true and sham acupuncture seem to increase the release of endogenous opioids, and we see that effect occurring in the ascending pathways and a segmental effect occurring in the spinal cord as well as in the descending modulating pathways mediated via dynorphins serotonin and norepinephrine. However, the effects of true acupuncture on the mu-opioid binding sensitivities are different from that of sham acupuncture.
In addition to this, we have imaging studies that have been conducted since the 1990s, and a recently published meta-analysis by Huang et al,17 which showed that while there is a problem with heterogeneity of these studies, they were able to conclude that the brain response to acupuncture encompasses a broad network of regions consistent with somatosensory affective and cognitive processing.
Overall, the neurophysiological evidence shows that acupuncture treatments affect the CNS in ways that are beneficial, long lasting, and unique to true acupuncture treatments. The neurophysiological evidence is also beginning to explain why we see different degrees of clinical effectiveness of acupuncture in conditions as diverse as gastrointestinal disorders, pain, and psychiatric conditions.
We have a lot more to learn and, far from being discouraged by this conflicting evidence in the literature, we should be excited by how much acupuncture has challenged and taught us about our understanding of human physiology. Does acupuncture work? Yes, according to the literature. Does acupuncture have unique and beneficial mechanisms of action on our neurophysiology? Again, I believe that the accumulative answer to that is yes.
The abovementioned discussion was about what's going on in the CNS with acupuncture. There are a couple of other theories about how acupuncture may be effective. The one most commonly cited is work is that of Helen Langevin,18 where she writes about the network of acupuncture points and meridians viewed as representations of a network formed by interstitial connective tissue and that there has been an 80% correlation of the acupuncture points where the intramuscular connective tissue planes.
The needle grasp is a result of a winding of connective tissue and causes a tight mechanical coupling between the needle and the tissue, and there's mounting evidence that this mechanical transduction can be translated into a variety of cellular and extracellular events. The 2 major models are the neurologic model, which is by far the most accepted and studied, and the connective tissue model.
Again, this is an evolving area. We have a lot more to learn, and I completely agree with Dr. Helms that we don't want to be locked into the evidence-based approach that we fail to understand the true clinical benefits that acupuncture has shown repeatedly over thousand years of practice and that we see ourselves in day-to-day practice in our offices.
DR. BERMAN: Apart from summarizing the mechanisms, Dr. Kaplan, I think you mean that when we're talking about evidence-based medicine, it's not just about the efficacy shown by randomized control trials. There's a wider range of methodologies and diseases to consider, depending on the question being asked. This is true of all medicine, including acupuncture, and if we narrow it down too much, we may fail to reap the benefits of using a very valuable tool as part of medicine.
DR. KAPLAN: I think you're absolutely correct. The other thing that we need to keep in mind is that the evidence-based research itself is a very limiting concept because we keep finding new mechanisms and understanding new subtleties about how the nervous system is working, how our physiology works, and then we're able to go back and say, "Ah, that's the mechanism via which this is happening." This whole topic about mu-opioid receptors is actually a breakthrough in terms of understanding how acupuncture may affect the CNS, which is unique and different from the way that sham does.
DR. BERMAN: What do you think are the cutting-edge research questions that still need to be answered as we go forward, questions that could not only inform us of how acupuncture works but could also affect clinical practice?
DR. KAPLAN: One of the areas that I've been particularly focused on is the microglial cells and their impact as the ultimate transducers between psychological stress, which gets translated into neurologic damage; and physical stress such as traumatic brain injury; as well as infectious stress, which also creates problems with neuroinflammation and neurodegeneration in conditions such as chronic pain and chronic illness.
We have seen evidence that acupuncture is actually neuroregenerative in some circumstances, certainly from some of the carpal tunnel studies that have been performed. We know that the microglia are involved in neuroregeneration; therefore, studying the effects of acupuncture on microglia may give us much more insight into how acupuncture works. This would be one area that I think should be focused on.
DR. BERMAN: Dr. Helms or Dr. Lao, any questions you think still need to be answered that can really make a difference?
DR. LAO: I agree with everything you have already said, but I think I'll add one point: we need more translational studies on how to apply the scientific information to our daily practices in order to enhance the effectiveness of acupuncture treatment. We did some studies in which the effectiveness of a combination of conventional medication and acupuncture was evaluated. We found that the effectiveness of the combined therapy was much higher than that of acupuncture or the medication alone. Maybe, in the future, the research should be designed to answer the question of whether acupuncture reduces the side effects of a medication, resulting in enhanced effectiveness of both medicine and acupuncture.
DR. BERMAN: I would add one point that goes along with that: we need to get a better idea of the responders and nonresponders to acupuncture. We could begin to address this by setting up some pragmatic clinical trials with the idea of comparative effectiveness research in actual settings of clinical practice as well as cost effectiveness. Further, we could determine who responds, and we can include imaging and genomics assessments as part of the biomarkers that we're analyzing.
Dr. Kaplan, do you have any final comments you want to add?
DR. KAPLAN: In terms of additional research, our thinking has been very much from a Bohr atom perspective [Bohr was a physicist who originally described the atom like a small solar system with electrons neatly orbiting the nucleus of the atom is a fixed orbit. This is a cartoon approximation of reality.] in terms of how the nervous system works, and we need to move toward a more quantum understanding. The whole field of neuroimaging is moving toward the concept of neuro-networking and trying to understand how the different regions of the brain interact with each other. I think that's going to show a lot of promise even in terms of how acupuncture is affecting the system.
I also think that, as you mentioned briefly, the cost effectiveness research is extremely important. Integrating acupuncture into conventional medical practice has the potential, at least to significantly reduce cost to the patient and side effects of medications. I think studies need to be conducted on this issue. I'm optimistic these studies will confirm what we have witnessed in clinical practice.
DR. HELMS: Just a comment on that, Dr. Kaplan. You first need a model environment where acupuncture is fully integrated into a broad-based clinical setting, not individual practices. That's the first hurdle to overcome before one looks at the impact of reducing reliance on pharmaceutical products or cutting back on the frequency of office visits and referrals to specialists.
DR. KAPLAN: I completely agree with you. I think that's a challenge that we need to potentially take on in the future, but it's something to be looking towards as we're going to have to be more cost effective and more cost conscious in our treatment of a variety of diseases. I think acupuncture has a significant role to play here but we are not ready to perform those studies yet. We need to start to think about them and how they can be accomplished.
DR. HELMS: In the past, we have thought of acupuncture as a treatment for chronic conditions, but one of the biggest problems we face in the military today is trauma. It could be possible to compare management outcomes at military facilities that have integrated acupuncture into their trauma treatment with those that have not.
DR. BERMAN: Here is where the military comes into play. They have proposed a move towards expanding availability of acupuncture immediately following trauma and then follow that through with intermediate and long-term care facilities. If this approach succeeds, it would create an environment in which those issues of acute, sub-acute, and chronic consequences of trauma could be evaluated.
DR. LAO: In ancient literature, early acupuncture was largely used for emergency medicine, particularly in the ancient times when patients were unconscious or in conditions such as fainting or convulsions where they could not be treated with oral medicines. There is a large body of ancient literature that has documented this use.
DR. BERMAN: I want to thank all of you for participating in this discussion; it's been a real pleasure.