Filling in the Acupuncture Jigsaw Puzzle.

Western medical practitioners often express scepticism about the role and validity of acupuncture as a therapeutic technique, despite the fact that it has been a part of traditional Chinese medicine (TCM) practice for more than 2000 years. Their uncertainty reflects in part difficulties that have been experienced in providing convincing proof to support the wide-ranging claims made regarding the benefits of acupuncture that it can be applied for the treatment of a seemingly endless list of conditions, extending from infectious diseases, to cancers, to metabolic, psychiatric, and other illnesses (1). It also reflects apparent discrepancies between TCM theories about the supposed mechanisms of action of acupuncture and Western science, which has been unable to find histological or physiological evidence for concepts such as qi and the theory of meridians. Despite the scepticism, over time, compelling evidence has accumulated that acupuncture is indeed an effective treatment for at least a small number of conditions, including notably pain syndromes and nausea (2, 3). In addition, physiological studies, enhanced by the advent of reliable animal models, have suggested a range of possible pathways of action, even if uncertainty has persisted about the specificity of the effects seen with respect to particular acupuncture points and techniques. The pathways are nowthought to comprise a rangeofmechanismsat various sites of action, including peripheral (eg, axon reflexes, neuropeptides, local endorphins), spinal (eg, gate control, propriospinal inhibition, etc), supraspinal (eg, sympathetic nervous system and effects on the hypothalamicpitituary-adrenal [HPA] axis), and central (eg, paraventricular nuclear, locus ceruleus, periaqueductal gray, and cortical) (4–6). Among the clinical conditions, about which claims of benefit from acupuncture have been made but which have remained controversial, are anxiety and depressive states. It is well recognized that many sufferers of these conditions use complementary and alternative medicines (7) and that a number of studies have supported the possibility of beneficial effects. However, a systematic review in 2007 concluded that, despite the positive findings, methodological deficiencies limit the conclusions that can be drawn about the efficacy of acupuncture in the treatment of anxiety and depression, (8) and especially the ability to exclude placebo or “expectancy” effects (9). It is agreed that, as with the other conditions, there remains a need for improved methodologies, larger studies, better standardization of treatments, and more rigorous control processes. On the other hand, an expanding body of evidence has supported claims for a physiological basis for an effect of acupuncture on stress responses and anxiety. Functional magnetic resonance imaging studies in humans have demonstrated activation of specific central nervous system pathways known to be associated with pain perception and stress, including the limbic system and subcortical gray structures (10). Animal models focusing on a limited number of clearly defined acupuncture points, including, especially, the so-called stomach 36 (St36) (also known as Zusanli) point, have assisted with the standardization of experimental procedures and supported the generation of an array of commensurable data. Studies of St36, in both humans and animal models, have shown effects on the HPA system and other brain structures, mediated through changes in neuropeptide Y expression and a variety of other neurotransmitters, endogenous opioid-like substances, and second messenger pathways (11–14).