Research Article: Prolonged Repeated Acupuncture Stimulation Induces Habituation Effects in Pain-Related Brain Areas: An fMRI Study

Date Published: May 12, 2014

Publisher: Public Library of Science

Author(s): Chuanfu Li, Jun Yang, Kyungmo Park, Hongli Wu, Sheng Hu, Wei Zhang, Junjie Bu, Chunsheng Xu, Bensheng Qiu, Xiaochu Zhang, Jie Tian.


Most previous studies of brain responses to acupuncture were designed to investigate the acupuncture instant effect while the cumulative effect that should be more important in clinical practice has seldom been discussed. In this study, the neural basis of the acupuncture cumulative effect was analyzed. For this experiment, forty healthy volunteers were recruited, in which more than 40 minutes of repeated acupuncture stimulation was implemented at acupoint Zhusanli (ST36). Three runs of acupuncture fMRI datasets were acquired, with each run consisting of two blocks of acupuncture stimulation. Besides general linear model (GLM) analysis, the cumulative effects of acupuncture were analyzed with analysis of covariance (ANCOVA) to find the association between the brain response and the cumulative duration of acupuncture stimulation in each stimulation block. The experimental results showed that the brain response in the initial stage was the strongest although the brain response to acupuncture was time-variant. In particular, the brain areas that were activated in the first block and the brain areas that demonstrated cumulative effects in the course of repeated acupuncture stimulation overlapped in the pain-related areas, including the bilateral middle cingulate cortex, the bilateral paracentral lobule, the SII, and the right thalamus. Furthermore, the cumulative effects demonstrated bimodal characteristics, i.e. the brain response was positive at the beginning, and became negative at the end. It was suggested that the cumulative effect of repeated acupuncture stimulation was consistent with the characteristic of habituation effects. This finding may explain the neurophysiologic mechanism underlying acupuncture analgesia.

Partial Text

Acupuncture, an ancient healing technique that originated in China, is used by millions of patients in many countries [1]. Continuous use of acupuncture in East Asia and more recently throughout the world has led to the assumption that acupuncture is a relatively effective and safe procedure. However, with the call for evidence based medicine, acupuncture has been tested at the forges of modern medicine [2]. Understanding the physiologic basis of acupuncture is critical to producing reliable results. Proposing and testing ideas about the underlying mechanisms of acupuncture could eventually lead to a real understanding about how acupuncture does work [3]. However, for the present it remains to be seen whether we are dealing with a specific physiological response of the brain to acupuncture, or with non-specific reactions to an undifferentiated stimulus [1]. In recent 20 years, fMRI studies have been extensively conducted to investigate the neurophysiologic mechanism of acupuncture. Although it is generally agreed that the brain and nervous system play a leading role in processing acupuncture stimuli [4], [5], the specific mechanism underlying the therapeutic effects of acupuncture is still under debate. Some researchers [5]–[10] proposed that the deactivation of the limbic-paralimbic-neocortical system was crucial to producing acupuncture’s therapeutic effects while some others [11] argued that these deactivations did not occur reliably and suggested that brain responses to acupuncture were activation-dominated.

Based on self-report, no subjects fell asleep during the experiment. The degrees of De-qi sensations such as soreness, numbness, fullness, aching, spreading and heaviness at both sides of acupoints were recorded and presented in Figure 2. The brain responses to acupuncture stimulation in the first run, the second run, the third run, and the aggregated runs were quite different (Figure S1), and the brain responses to the six blocks of acupuncture stimulation were also extremely varied (Figure S2). The brain response in the first block was the strongest. Only positive responses (activations) in the first block were found above the threshold (P>0.005, α = 0.01, Cluster size = 21, Monte Carlo Method) after multiple comparison correction. These activated areas in the first block included the thalamus, the second somatosensory cortex (SII), the middle cingulate gyrus, the paracentral lobule, the inferior frontal gyrus, the superior frontal gyrus, the precentral gyrus, the precuneus, the inferior parietal lobule, the superior temporal gyrus, the middle temporal gyrus, the fusiform gyrus, and the cerebellum (see Table 1, Figure 3).

Our results demonstrated that the brain responses to acupuncture stimulation were time-variant, in which the brain responses to the initial stimulation were the strongest. This finding is consistent with the previous acupuncture fMRI studies [18], [19]. The most interesting finding in this study was that the prolonged repeated acupuncture stimulation induced habituation effects in some pain-related brain areas. In these areas, acupuncture instant effects in the initial stage demonstrated as extensive brain activations and cumulative effects in the process of repeated acupuncture stimulation demonstrated as an interesting characteristic of bimodal habituation, i.e. positive brain response appeared at the beginning of acupuncture stimulation, and then it declined and became negative in the last.

This study demonstrated that the cumulative effect of prolonged repeated acupuncture stimulation was a kind of habituation effects in pain-related brain areas, where the positive response appeared at the beginning of acupuncture stimulation, and then declined and became negative in the last. It suggested that these increasingly decreased changes of brain response to acupuncture stimulation over time were a kind of habituation effects, a kind of acupuncture cumulative effect. This finding might be useful to explain the neurophysiologic mechanism underlying acupuncture treatment, especially to analgesia, because all brain areas showing acupuncture cumulative effects in current study were related to pain perception. Anyway, further investigations were necessary in order to provide more evidence to support the presumption that acupuncture analgesia was due to the habituation effects of acupuncture stimulation.