(1995; 68 pages)
Annex 1. Strategic approaches to randomized controlled clinical trials
The neurophysiology of acupuncture has been investigated extensively and reviewed in detail. The principal suggestion is that acupuncture operates largely through neurotransmitters, particularly endorphin-related mechanisms. This argument has been supported almost exclusively by evaluating acupuncture in the context of acute pain within an animal model. These studies demonstrate conclusively that acupuncture’s effects are related to the release of a variety of neurotransmitters including natural opiates and, furthermore, that this effect is naloxone-reversible. Basic research work carried out has demonstrated conclusively that any noxious stimulus will result in endorphin release through the neurophysiological mechanism described as diffuse noxious inhibitory control (DNIC). Therefore DNIC represents a nonspecific physiological mechanism which triggers the natural opiate system in both man and experimental animals. There are some studies with human subjects which suggest that acupuncture is not always naloxone-reversible, but they do not fit the general weight of evidence available from animal models. It has been suggested that DNIC plays a relatively minor role in acupuncture analgesia and that other systems, mediated by serotonin and noradrenaline, may be more important.
It is quite probable that chronic pain has different underlying mechanisms from those involved in acute experimental pain in animals. Those working with pain clinics will be only too aware that empirical manipulation of the autonomic system can result in dramatic clinical improvement. In spite of the fact that we do not have a unified theory upon which to explain the mechanism of chronic pain, the empirical evidence available to us would suggest that the autonomic system plays an important, but as yet undefined role, in the complex phenomena involved.
The mechanisms of acupuncture involved in its use as a treatment for addictions almost certainly utilize the endorphin and encephalin systems. There are, however, no detailed studies which define the exact mechanism involved in smoking cessation. Again, it would be reasonable to suggest that the withdrawal symptoms experienced in almost any addictive process may be, at least in part, endorphin-mediated.
The mechanism of acupuncture in internal diseases, such as asthma, irritable bowel, and the treatment of symptoms such as nausea is completely unknown. Acupuncturists have hypothesized that the autonomic nervous system plays an important but as yet ill-defined part in the underlying mechanisms that are involved in the treatment of such internal problems. If we accept that acupuncture might affect the autonomic nervous system in some way, a crucial question now emerges: how is it that needling at some points can affect the autonomic pathways whereas needling at others does not, or does so to a much smaller extent?
It is likely that addictive processes are mediated through neurotransmission which includes the natural opiate systems. Consequently, if we observe clinically that there is no difference between real and sham acupuncture in the treatment of smoking cessation, it is reasonable to suggest that this may be because acupuncture is largely endorphin-mediated in this clinical context. Nonspecific needling may be having as great a clinical effect as specific needling techniques.
In the treatment of nausea however, a non-endorphin mediated mechanism is probably involved. The clinical trial evidence to date suggests that acupuncture has an effect and furthermore that point location is important; needling away from pericardium 6 does not seem to produce as great an effect. It is possible therefore that the theories that underpin traditional medicine relate to an empirical and pragmatic understanding of the autonomic nervous system and its detailed correspondences and effects on the body. If this suggestion is correct, then we would expect that within the treatment of purely internal and non-pain related problems, needling of particular areas, rather than just general stimulation, may be important. Therefore, a sham versus real model may be appropriate in this context.
The final group involves chronic pain. Here there is clear evidence that chronic pain is at least in part mediated through the neurotransmitter, but the empirical evidence suggests that the autonomic system is also important in maintaining a number of chronic pain syndromes. Therefore clinical trials involving acupuncture as a treatment for chronic pain will provide a mixed picture. Sham acupuncture will have some effect through DNIC and will therefore provide a greater effect than that expected from placebo alone. Real acupuncture will utilize the endorphin system but also a putative autonomic response and local trigger-point action, to produce additional effects and therefore an increased clinical response when compared to sham acupuncture. A comparison of acupuncture with placebo in a clinical trial will produce the most clear-cut results when attempting to evaluate acupuncture but point location (real vs sham) may also be important to test the validity of the specific theories concerning point prescription.