What leads to the powerful effects seen in the placebo/sham acupuncture groups compared to routine care in recent clinical trials? And how can we harness these effects more broadly for clinical care? To assess response expectancy as a potential source of ‘non-specific’ therapeutic effects, it is essential to develop a psychometrically sound measure that can be used in acupuncture research and clinical care. In this study, we extended our previous work and further validated a simple 4-item Acupuncture Expectancy Scale (AES) to measure subjects’ specific expectation about the outcomes of acupuncture therapy in English-speaking U.S. cancer patient populations. The scale is found to be reliable, valid, and is sensitive to change during treatment.
Several outcomes were different between this study and our previous research conducted in the Chinese acupuncture patient population.22
The American participants were mostly acupuncture naïve and there were substantial flooring effects in their responses to individual items with about 1/5 firmly believing acupuncture was unlikely to have any effect. In contrast, the Chinese participants were experienced with acupuncture and there were substantial ceiling effects in their responses, with many believing acupuncture would have significant positive effects. As suggested by our data, prior acupuncture experience may increase response expectancy towards acupuncture. Thus, the American/ Chinese differences may be related to the fact that the Chinese acupuncture patients were receiving acupuncture at the time of the survey. Secondly, the reliability coefficient of Cronbach’s alpha was substantially higher in this study compared to the original Chinese validation study (0.95 vs. 0.82). It is possible that for those patients who have had acupuncture, their rating of expectancy is modeled after the actual acupuncture experience, so the variability of endorsement for individual items was greater for the patients who have had acupuncture. Nevertheless, the differences noted in the two studies highlight how different cultures and prior experience with conventional and complementary therapies may affect the expectancy of acupuncture.
Several previous studies have focused on the role of expectancy on clinical outcomes of acupuncture in the context of clinical trials. Thus far, most studies26,27
found higher pretreatment expectancy was associated with greater clinical improvement as measured by validated disease outcome measures. However, the use of different types and often un-validated scales to measure expectancy makes it difficult to gain insight into the degree expectancy plays a role in pain and symptom relief. It is possible that expectancy may play a bigger or smaller role in various conditions,28
as the psychological state of the patient may vary by condition, such as for cancer as compared with chronic knee pain. Also, the use of the validated AES across the disease spectrum may be important to isolate the specific effect of expectancy for various diseases outcomes (e.g. pain, function, satisfaction) in acupuncture care. Such understanding may help clinicians understand for which disease or specific outcomes, expectancy may exert greater power in the clinical outcome for patients. This would allow more careful facilitation of positive expectancy in certain patients.
Our study also highlights that positive response expectancy is associated with increased use of therapies, both stated and actual in clinical trial context. As the use of acupuncture and other types of conventional or complementary therapies occurs in societal and cultural contexts, expectancy can be influenced by science, media, health care professionals, family and friends. Research using the AES with appropriate study designs may help uncover how social and scientific forces shape expectancy and affect the utilization of acupuncture, and ultimately affect clinical outcomes.
Recent advancement in neuroscience and imaging methods has increased the understanding of potential biological mechanisms of expectancy and placebo response. In a pharmacological paradigm, the expectancy of pain relief may be mediated via both brain opioid and dopaminergic pathways.29–32
Recent investigations in acupuncture yielded intriguing findings. In a fMRI study using expectancy manipulation and thermal pain model, Kong et al. found that although the acupuncture analgesic effect and expectancy-evoked placebo analgesia produced similar reductions in patient-reported pain, the neuro-pathways underlying such reports were distinct.21,33
Similarly, using C-carfentanil PET imaging, Harris et al. found that while both real and sham acupuncture produced similar clinical benefits for patients with fibromyalgia, the mechanism underlying the pain reduction was different -- real acupuncture increased both short- and long-term mu-opioid receptor (MOR) binding potential in multiple pain and sensory processing regions, while sham acupuncture actually resulted in only a small reduction of MOR binding potential.34
The above studies suggest that while real acupuncture may produce analgesia via peripheral to central, bottom-up modulation, expectancy (placebo effect) may induce analgesia via top-down, i.e., centrally mediated modulation. Using AES combined with advanced imaging techniques and clinical outcomes in actual disease models may help further elucidate the complex interaction between expectancy and specific efficacy of acupuncture needling in producing meaningful clinical outcomes. Such understanding will pave the way to better optimize the physiological effect of acupuncture needling and the psychological effect of setting appropriate outcome expectancy to produce clinical improvement of pain, symptoms, and functions.
Several limitations of our study need to be acknowledged. Our study participants were cancer patients and mostly female. Validation of the scale in other clinical and healthy populations is needed to learn how the scale will perform in other settings with different disease entities. Our scale was intended to measure specific expectancy towards acupuncture, so it may not capture other important cognitive processes such as trust and perceived barriers that may play important role in both use and efficacy of acupuncture. Furthermore, large prospective studies are needed to evaluate the predictive validity of this scale.
Despite the limitations, this study represents an incremental and necessary step in developing methods to uncover the mechanism of the “powerful placebo” effect seen in acupuncture research. The rapid development of neuroscience is likely to provide increased understanding of the biological mechanism of acupuncture. The development of a psychometrically sound measure of response expectancy related to acupuncture will further translate such mechanistic understanding into actual clinical context. The substantial non-specific effect seen in the previous acupuncture literature provides an impetus for effective utilization of such power in clinical care. Appropriate use of the AES combined with other newly developed biological markers may powerfully facilitate clinical and translational research that ultimately creates patient-centered integrative approaches to effectively ameliorate the suffering of chronic pain and other symptom distress.