Abstract
Abstract
Acupuncture is rapidly becoming part of mainstream medicine in the West and in the United States. A national survey shows that more Americans are using the modality now than they were a decade ago. Federal research funding has increased, and an extensive body of acupuncture research has been published, much of it with important clinical implications. Recent clinical trial and systematic review results clearly show acupuncture to be more beneficial than conventional standard care for many pain conditions, and basic scientific research has advanced our knowledge of acupuncture's mechanisms of action in a number of pathological conditions. While the current research is not without its problems and difficulties, the acupuncture research community has matured and is facing its challenges by developing better research methodologies, applying new technologies, and engaging in more creative and innovative translational research. This review discusses developments in the field.
Introduction
Clinical Acupuncture Research in Evidence-Based Medicine
Large-scale randomized clinical trials (RCTs) illustrate the status of clinical acupuncture research. In a phase III RCT on 570 patients with osteoarthritis (OA) of the knee, acupuncture performed significantly better than either placebo or education-only in function, pain, and global assessment. 5 In a three-arm RCT of 180 patients, postoperative surgical pain-free time, mean pain-free postoperative time, and mean number of minutes before medication requests were marginally longer for verum acupuncture than for non-insertion placebo (sham) acupuncture, and fewer patients in the treatment group requested pain medication, but there was no difference between verum acupuncture and sham acupuncture. 6 An RCT of 638 adults with chronic low-back pain (CLBP) compared individualized, standardized, and simulated (sham) acupuncture and usual care. All three treatment groups improved significantly compared to usual care, and after 1 year, scored better in a scale to measure dysfunction and had missed fewer usual activities, again, with no significant difference between sham and real acupuncture. 7 Several researchers also reported good results, using acupuncture to treat various pain conditions.8–14 In a multicentered, blinded RCT on CLBP in 1162 patients comparing verum acupuncture, sham acupuncture, and conventional therapy, acupuncture performed almost twice as well as did conventional therapy, 14 but, again, verum and sham acupuncture were not significantly different. This may be caused by procedures or conditions, as some trials do report significant benefits for verum acupuncture. In an RCT 15 of 424 outpatients with chronic shoulder pain, verum acupuncture produced greater improvement in shoulder mobility than sham acupuncture (as a control) both immediately after treatment and at 3 months. Systematic reviews, including a Cochrane review of 22 trials for headache, 16 showed positive results or trends for acupuncture for treating various kinds of pain, including chronic, back, and elbow pain; OA; fibromyalgia; temporomandibular joint disorder; and herpes zoster.17–38 Trials on non-pain disorders—such as insomnia, depression, nausea, and vomiting—also showed the benefits of acupuncture,39–64 and systematic reviews have been compiled on those conditions, as well as on irritable bowel syndrome, asthma, schizophrenia, leucopenia, stroke, addiction, enuresis, in vitro fertilization, and depression. Many of these trials showed positive outcomes or positive trends, but an equal number of trials were inconclusive, suggesting that more research is needed. Given that many factors may determine therapeutic outcome profoundly, the so-called negative outcomes produced in some RCTs may be false–negatives caused by nonspecific responses. More careful design and more innovative approaches should be considered to minimize such nonspecific confounders.
Basic Science Studies Using Animal Models
Recent animal research provides clear evidence of the role of antinociceptive limbic, hypothalamic, and brainstem networks in acupuncture analgesia.65,66 Animal studies on inflammatory pain suggest that electro-acupuncture (EA) activates the hypothalamus–pituitary–adrenal axis and neural circuits67–72 and is parameter-dependent. Low-frequency EA has antihyperalgesic and anti-inflammatory effects; high-frequency EA has potent but short-term antihyperalgesic effects alone.68,69 It has been reported that EA suppresses hyperalgesia and spinal Fos expression by activating the descending inhibitory system to inhibit transmission of noxious messages and hyperalgesia, 72 and that adenosine, a neuromodulator with antinociceptive properties, is released during acupuncture in mice. This suggests that that interfering with adenosine metabolism may prolong the clinical benefit of acupuncture. 73
Modern Technology: Acupuncture Mechanisms of Action in Human Subjects
An important trend in clinical acupuncture research is the use of modern technology to explore acupuncture mechanisms of action. Using techniques such as positron emission tomography and functional magnetic resonance imaging (fMRI), researchers can monitor neurophysiological brain effects 74 to show the effects of acupuncture. In a carpal tunnel (CTS) study, surface-based and region of interest–based analyses demonstrated that fMRI activity in contralateral Brodmann areas 1 and 4 was greater in patients with CTS than in healthy adult controls but that acupuncture significantly decreased activity in those areas. 75 Needling effects have also been studied with the new techniques: brain fMRI blood oxygen level–dependent signals show that Deqi causes significant deactivation while acute pain produces a mixture of activation and deactivation. 76 A study also shows that needle grasp is the result of mechanical coupling between the needle and connective tissue: Tissue winds around the needle during rotation, and manipulation transmits a mechanical signal to connective-tissue cells via mechanotransduction; this may explain some of acupuncture's local, distal, and long-term effects. 77
Challenges of Acupuncture Research
Despite a rise in high quality acupuncture RCTs, researchers face many challenges. Adequate controls, blinding, and point selection; the relative skills of practitioners performing the acupuncture; and the timing and choice of outcome assessments 78 are among the issues that must be considered. For example, the commonly used controls, wait-list, noninsertion sham, and needle-insertion sham, seem to produce different results. A breakdown of acupuncture RCTs published in 2006 and 2007 by control found that outcomes were mostly positive, compared to wait-list or noninsertion sham (13 of 16 and 6 of 7, respectively) and that needle-insertion sham produced the fewest (2 of 8 positive results. 14 This suggests that acupuncture can “trigger the neuronal mechanisms involved in diffuse noxious inhibitory controls.” 79
Discussion
The Society for Acupuncture Research acknowledges two paradoxes: (1) True (verum) acupuncture often does not significantly outperformed sham acpuncture; and (2) needling effects, if clearly evident in basic science studies, are not always so in clinical trials. The Society suggests that combined “top–down” multicomponent “whole-system” interventions and “bottom–up” mechanistic studies focusing on how individual treatment components interact and translate into physiological outcomes will allow efficacy, effectiveness, and qualitative measurements that strengthen the evidence base for what is, at its root, a very complex intervention. 80
Conclusions
Acupuncture has gained in popularity because of its reputation for efficacy and safety. RCTs support acupuncture's safety and effectiveness for treating various disorders, particularly chronic pain conditions, and recent preclinical basic science studies and technological innovations have advanced our knowledge of acupuncture's mechanisms of action significantly. Our research community, as it matures, becomes ever more ready to face research challenges, engage in meaningful scientific discussion, and search together and with the wider medical community for solutions to the pressing questions regarding acupuncture, its effects, and its mechanisms.
Footnotes
Disclosure Statement
No competing financial conflicts exist.