Physiological mechanisms of acupuncture: Beyond placebo?

Individuals who have chronic pain that does not respond well to conventional medicine often seek alternative treatments for which medical science does not have an adequate explanation of their effects [2]. In some quarters such treatments are viewed with suspicion, and it has been proposed that the efficacy of alternative therapies can be mostly attributed to placebo effects [9]. While scientific evidence for the effectiveness of many alternative treatments is lacking, the use of acupuncture to relieve pain has prompted a large degree of interest in the medical research community. The efficacy of acupuncture in chronic pain is inconsistent across studies. However there is enough evidence of different physiological effects to encourage research into the mechanism(s) through which acupuncture might improve pain. Two closely linked candidate systems by which acupuncture may exert its effects are the hypothalamic–pituitary–adrenal (HPA) axis, and the endogenous opioid (EO) system. These systems are important mediators of the stress response to pain and other threatening stimuli [5], and considerable evidence implicates abnormalities in these systems in chronic pain conditions such as fibromyalgia [3], which are thought to involve psychosocial factors in their aetiology. Recent neuroimaging evidence has shown that the relationship between the neurochemical changes within the endogenous l-opioid system [4] and the long-term pain-relieving effects of acupuncture appear to be opposite to that observed with placebo or sham treatments [17], even though treatment and sham/placebo treatments produce almost identical reductions in perceived pain. These observations suggest that acupuncture and placebo treatments, in fact, operate according to different mechanisms, with only acupuncture exerting long-term therapeutic effects on the EO system. However, the effect of acupuncture on the HPA system is far from clear. Although cortisol release is one of the consequences of HPA system activation, different studies have shown opposite responses of cortisol release in response to acupuncture. For example, normal individuals show opposite cortisol responses to those with chronic pain conditions [11,13]. This suggests that if the HPA axis contributes to the efficacy of acupuncture, its role is more complex than simply deactivating this system. Rather the contribution may depend on the population being studied. One mediating factor may be the presence or absence of anxiety and depression, which are known to predict the onset and severity of chronic pain [8]. There is a general belief that hyperactivity of the HPA axis is associated with depression and anxiety disorders [15], an imbalance that may be expected to be corrected after appropriate therapy. This highlights the need for detailed psycho-physiological profiling of patients entering research studies that attempt to elucidate the mechanisms of new treatments. Although research has already shown some efficacy of acupuncture in treating the pain of osteoarthritis (OA) [14], to date no one