Do the Neural Correlates of Acupuncture and Placebo Effects Differ?

This important scientific review addresses one of the most fundamental questions in acupuncture research: is there a real neurologic difference between the effects of true acupuncture and the placebo effect? Using advanced neuroimaging techniques such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), electroencephalography (EEG), and magnetoencephalography (MEG), the investigators examined how the brain responds differently to real acupuncture versus placebo interventions. The research was based on animal studies that demonstrated that therapeutic acupuncture is mediated, at least in part, by endogenous antinociceptive networks involving opioid and monoaminergic neurotransmission. These networks include the brainstem, thalamus, hypothalamus, and pituitary actions.

Human neuroimaging data revealed that acupuncture stimulation modulates a broad network of brain regions, including the primary and secondary somatosensory cortices, anterior cingulate, prefrontal cortex, insula, amygdala, hippocampus, hypothalamus, periaqueductal gray, and cerebellar vermis. A particularly interesting finding was the deactivation of limbic regions observed in fMRI studies during stimulation with real acupuncture, a phenomenon attributed to decreased neuronal activity in these areas. Studies that explored how acupuncture alters the brain response to painful stimuli showed that both true and sham acupuncture reduced pain responses in the thalamus and insula in patients with fibromyalgia. PET data using carfentanil supported the involvement of μ-opioid receptors in acupuncture analgesia.

As for placebo effects, earlier research with naloxone suggested that placebo analgesia is partially mediated by limbic and brainstem opioidergic networks. fMRI studies have shown that placebo analgesia recruits opioid-sensitive brain regions, including the periaqueductal gray, rostral anterior cingulate, thalamus, insula, and amygdala — many of which overlap with those modulated by acupuncture. To dissociate the specific effects of acupuncture from placebo effects, several studies used sham needles and expectancy manipulations. It was found that true acupuncture induced greater increases in brain response in the ipsilateral insular cortex compared with covert sham.

Differences in modulation of the dorsolateral prefrontal cortex and rostral anterior cingulate may support nonspecific pain expectation, while modulation of the amygdala, insula, and hypothalamus may demonstrate some specificity of acupuncture. In patients with carpal tunnel syndrome, compared with healthy controls, true acupuncture produced a more pronounced decrease in signal in the amygdala and an increase in signal in the hypothalamus. The authors hypothesized that these limbic areas may reduce pain through cooperative modulation of affective/cognitive activity and the autonomic nervous system. It is important to note that placebo effects are generally short-lived, while the clinically relevant effects of acupuncture analgesia can be cumulative across multiple treatments and extend gradually beyond the duration of each session.

In fact, long-term acupuncture treatment in patients with chronic neuropathic pain altered cortical somatosensory processing and produced beneficial changes in somatotopy. The limitations of the studies include the difficulty in replicating acupoint specificity, variability in needling techniques and data processing methods, and the fact that most neuroimaging work involved only a single application in healthy individuals. Future work using PET imaging may help to elucidate the relative contributions of opioidergic and monoaminergic transmission in therapeutic acupuncture.