Acupuncture treatment has been tested and clinically validated in many diseases [1,2]. Acupuncture’s actions have been traditionally explained based on the meridian theory. The original concept of meridians is a path for the flow of qi and blood, and the key concept is that meridians are ‘connecting remote body sites’ and ‘delivering disease-related or treatment-related sensations’ [3,4]. The former developed and supported the theory of remote indications of acupoints and the latter caused clinicians to emphasize deqi sensations and pulse palpation skills. The distinctive biophysical features of the meridian system, such as enhanced electrical conductance [5], connective tissue planes [6], nitric oxide concentration [7], and neurogenic inflammatory response [8] have recently been studied. However, the concept of the meridian system requires further clarification.

Functional brain imaging techniques have clarified the neural mechanisms underlying acupuncture actions [9,10]. Meta-analyses of neuroimaging studies have shown that acupuncture stimulation produces common brain activations in the sensorimotor cortical network and deactivations in the limbic-paralimbic-neocortical network [9,11]. In addition, acupuncture treatment at disease-implicated acupoints modulates the activity of the disease-related neural pathways, indicating that alterations in regional brain activity may mediate the therapeutic effects on target organs [12]. The literature regarding neuroimaging on acupuncture has steadily increased [13], and acupoint specificity has been explored in many studies [14-16]. However, despite decades of efforts, acupoint specificity has not been fully supported by biomedical approaches [17,18].

The origin of the meridian system is closely associated with acupuncture’s treatment effects and serves as an empirical reference in the clinical setting [19]. Thus, knowledge regarding the origin and clinical significance of the meridian system should precede understanding acupuncture’s mechanism of action in humans [19]. Acupuncture uses needles to stimulate a particular part of the body, called acupoints, for treatment. The core principle of the meridian system is connections between different body areas (e.g., hand–head), between organs (e.g., heart–small intestine), and between body parts and organs (e.g., visceral organs–back). In addition, meridians are associated with disease-specific treatment sites [20] and have been widely used to explain the remote effects of acupuncture treatment [3]. For example, the observation of many acupoints along a certain “line” sharing similar indications led acupuncture practitioners to categorize them based on their locations [20]. The meridian system represents constellations of acupoints that have common therapeutic effects for specific symptoms in the body. Taken together, the meridian system can help to identify spatial patterns of symptoms in the body and in selection of relevant acupoints. However, there has been no discussion of how acupuncture affects the body and brain in the context of the meridian system’s original meaning.

This review discusses how acupuncture affects the body and the brain. The importance of acupuncture’s actions in the body should be considered from the perspective of the whole system, which revisits the meaning of the meridian system. With data science technology, new trends in acupuncture research are emerging. This article will discuss current trends in acupuncture research as well as potential future directions.

1. Effects of acupuncture on the body

In traditional East Asian medicine, acupuncture practitioners’ medical decisions are typically based on a clinical interview, physical examination, pattern identification of symptoms and signs, diagnosis, and prescription of appropriate acupoints [21,22]. The underlying principle in acupoint selection is mainly based on the meridian system, which has common clinical implications regarding the constellations of acupoints [3,23]. Visualization of acupoints and meridians on the human body surface is achieved by relying on ancient infographics of the associations between treatment at each point and the subsequent clinical outcome changes [19,20], and remains a valuable approach in meridian studies [24-27].

The application of data science technology to clinical research on acupuncture treatment shows that a theoretical model of the indications of acupoints is associated with the meridian lines [24,27]. The essence of the meridian system can help explore point specificity at the whole-body level during acupuncture treatment. In previous studies, this approach required reliable and meaningful clinical data that included details of acupuncture interventions and clinical outcomes. Abundant clinical data regarding acupuncture treatment is available from bibliographical data or medical records. When the acupoints are analyzed using modern methodologies, the meridian theory should be updated and developed to reflect changes in technology and accumulated medical experiences.

2. Spatial patterns of acupoint indications based on the literature

The meridian system is an empirical reference in acupuncture. Based on quantitative clinical data, the most frequently used acupoints are BL23, BL25, BL40, and BL60 in the treatment of low back pain, which indicates that the bladder meridian and its key points are widely used to treat low back pain. The acupoints were depicted based on the frequency of their use, and biomedical information can provide interpretable maps of which acupoints are most useful to treat low back pain [19,20]. Lee et al. determined how acupoints have been used together for the treatment of low back pain, and network analysis for combinations of acupoints showed the principle of acupuncture combination, which is a basic clinical skill for effective acupuncture treatment [20].

In several studies, data mining algorithms were used to determine the patterns of symptoms and treatment methods within various fields of research [28]. Using term frequency-inverse document frequency methods, the spatial patterns of the indications of each acupoint in the classical Korean medical text are visualized on a body map [3,29]. For example, acupoints on the Hand-Yang meridian are associated with the head, face, ears, eyes, nose, mouth, and teeth, and acupoints on the Hand-Ying meridian are associated with the heart and chest area [3]. However, the available spatial information for the body in the literature is limited because there is minimal detailed information regarding the spatial location from large-scale clinical investigations.

3. Spatial patterns of acupoint indications based on clinical data

Acupoints have both specific and non-specific indications [25,27]. These indications are primarily established based on the meridian theory, meaning they have spatial patterns of symptoms in the human body. As meridian also concerns delivering sensations, disease-related sensations are also important in acupoint indications. In a recent study, 75 patients with chronic pain were asked to sketch the localization of their symptoms on body schemes using the Bodily Sensation Map [30]. Combining the selected acupoints and symptom maps, the statistical parameters of the associations between acupoints and spatial symptom information were estimated. The spatial indication patterns of the representative acupoints on the human body template were further visualized. The first group of patterns was distant from the location of the acupoint and strongly associated with the corresponding meridian’s route. The second group of patterns was near the acupoint location, the majority of which were located in the trunk. Extensive investigations of the spatial patterns of acupoint indications combined with the Bodily Sensation Map would be a novel way to explain the point specificity of acupuncture treatment based on the meridian system (Fig. 1) [30].

Figure 1. Acupuncture action in the body and brain. Spatial patterns of the indications of an acupoint (the SI3 acupoint) using the Bodily Sensation Map tool. Common brain responses to acupuncture stimulation. Data were modified from previous studies [9,30].

Machine learning techniques can be used to determine the association between the symptoms and acupoints without explicit structural knowledge [21]. Implicit knowledge using large-scale clinical data can guide practitioners to appropriate acupoints for specific patients.

1. Brain activation patterns to acupuncture stimuli

Several convergent neuroimaging results have expanded the understanding of neural mechanisms of acupuncture in the brain [13]. Research on acupuncture from neuroimaging methods is categorized as follows: (1) studies on the correlation between treatment effects of specific acupoints and corresponding brain activities; (2) studies on the effects of different locations of acupuncture stimulation (acupoint versus non-acupoint or one acupoint versus another acupoint) on neural activity patterns; and (3) studies on the changes in brain activity after long-term acupuncture treatment [10]. Stimulations at different acupoints elicit overlapping brain responses in cortical and subcortical brain regions, including activation in the sensorimotor cortical network and deactivation in the limbic-paralimbic-neocortical network [9,11]. However, psychosocial factors, such as expectation and context, also contribute to brain activity following acupuncture stimulation [31,32]. The scientific evidence for the neural signatures of acupuncture in humans requires further evaluation.

2. Top-down modulation of acupuncture treatment

The sensations induced by acupuncture rely on the bottom-up signals from various receptors located on the skin and the reciprocal interaction of top-down modulation of the brain upon stimulation [33]. For example, in a recent study, cutaneous electrical stimulation resulted in greater deqi sensation and brain activations in the anterior insula, pre-supplementary motor area, and secondary somatosensory area [34]. When individuals felt the rubber hand as their own body, acupuncture stimulations, even on the artificial limb, resulted in a deqi sensation and brain activations, especially in the interoceptive system [33]. Furthermore, expectations of the physiological responses influence the perceived somatic sensation for acupuncture stimulation [35]. A new form of placebo acupuncture, so-called phantom acupuncture, produced significant acupuncture sensations, autonomic responses [36], and brain functional changes through a visual display of acupuncture treatment [37]. Recently, Cao et al. [38] showed that video-guided acupuncture imagery treatment significantly increased the pain threshold when the participants watched a video of acupuncture and imagined the treatment being applied to their bodies. The results of these studies demonstrate that the top-down process can induce both acupuncture sensations and clinical effects.

The effects of acupuncture stimulation without peripheral inputs might be associated with imagination (if the participants successfully imagined the treatment being applied to their body) or vicarious sensations (if the participants failed to imagine that the treatment was applied to them but instead felt what the person in the video was supposed to feel). Accentuated bodily attention-related brain responses are highly associated with salient components of acupuncture analgesia [39]. Even without any physical stimulations to the body, enhanced attention around a certain part of the body results in activations in the salient interoceptive-autonomic network and deactivation in the brain’s default mode network [40]. In Western medical acupuncture, which involves needle insertion based on current knowledge of anatomy, physiology, and pathology [41], traditional theories are not considered necessary. However, the importance of acupuncture in the body must be considered from a whole-system perspective.

3. Placebo acupuncture

Understanding the neurological substrates and mechanisms underlying the effects of acupuncture allows for its integration into modern medicine. Acupuncture can be a complex intervention that incorporates more than just a needling process [42], and can be a multimodal sensory stimulation that interacts with various factors [43]. Biological approaches have resulted in various cognitive components of acupuncture treatments, including treatment expectations, which influence the physiological responses and clinical effects of acupuncture treatment. Understanding the neural underpinnings of the cognitive components of acupuncture treatment may further scientific investigation of the effects and underlying mechanisms of acupuncture. Conversely, in terms of biomedical knowledge, placebo acupuncture should not be disregarded, but scientific knowledge of this phenomenon is currently lacking [44,45].

Acupuncture treatment can effectively stimulate certain parts of the body and induce deqi sensations along the needle or affected body parts. Placebo needle administrations can activate (although less robustly) the somatosensory system and induce regulatory mechanisms similar to actual acupuncture needling [46]. Placebo needles can be as effective as actual acupuncture as they provide a low-dose acupuncture stimulation [44,45].

Both acupuncture and placebo needles can induce sensations around certain parts of the body [40,47]. In a qualitative interview study, patients treated with placebo needles described enhanced touch sensations, including warmth, tingling, or flowing [48]. Focus on a particular bodily location can have dynamic attentional filtering effects on early sensory cortices, even before the area is directly touched [46]. Because the placebo needles elicit enhanced touch sensations associated with an embodied healing mechanism, these sensations could further influence the patient’s interpretation of a specific stimulus and the process as a whole [48]. As acupuncture functions as a somatosensory-guided mind-body therapy, placebo needles could similarly enhance bodily attention around the site and exert potential actions through endogenous pain modulation in the brain [44].

In summary, the significance of the meridian system should be explored based on its original meaning, interconnections between particular diseases and acupuncture sites, and somatic sensations associated with treatments and diseases regardless of anatomical or biological features. Investigating the principles of the meridians provides a better understanding of acupoint selection, which can improve clinical efficacy.

This research was supported by the Korea Institute of Oriental Medicine (no. KSN1812181) and the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2021R1F1A1046705).

ISL and YC conceived the study ideas and drafted the manuscript.

No ethical approval was required for this manuscript as this study did not include human subjects or laboratory animals.

Not applicable.

The authors declare no conflict of interest.