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A systematic review and coordinate-based meta-analysis of fMRI studies on acupuncture at LR 3

Rao et al. · Frontiers in Neuroscience · 2024

🧠Neuroimaging meta-analysis👥n=319 participants🏅High scientific impact

Evidence Level

STRONG
85/ 100
Quality
4/5
Sample
4/5
Replication
4/5
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OBJECTIVE

To investigate the neurobiological mechanisms of acupuncture at the LR-3 point (Taichong) through functional neuroimaging

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WHO

319 right-handed healthy adults from 10 independent studies

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DURATION

Search up to June 2023, varied neuroimaging studies

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POINTS

LR-3 (Taichong) — point located on the foot, important for emotional regulation

🔬 Study Design

319participants
randomization

Real acupuncture

n=163

stimulation at the true LR-3 point

Control/Sham

n=156

sham points or baseline state without stimulation

⏱️ Duration: Meta-analysis of studies published up to June 2023

📊 Results in numbers

Z=3.021

Right postcentral gyrus activation

Z=2.467

Left thalamus activation

Z=2.49

Left middle frontal gyrus activation

Z=2.086

Right superior frontal gyrus activation

p<0.00005

Correlation with needle retention time

📊 Outcome Comparison

Brain activation intensity (Z-score)

Right postcentral gyrus
3.021
Left thalamus
2.467
Middle frontal gyrus
2.49
Superior frontal gyrus
2.086
💬 What does this mean for you?

This study demonstrated that acupuncture at the LR-3 point (located on the foot) activates specific brain areas related to pain processing, emotional regulation, and cognitive functions. This provides scientific evidence of how acupuncture works in the brain, explaining its therapeutic effects for pain and emotional disorders.

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Article summary

Plain-language narrative summary

Acupuncture is an ancient practice of traditional Chinese medicine that, in recent decades, has gained growing recognition in Western complementary medicine. Although it is widely used for the treatment of pain, depression, anxiety, and various other conditions, the brain mechanisms by which it works are still not fully elucidated. The LR-3 acupuncture point, known as Taichong, is located on the liver meridian and is considered fundamental for regulating emotions, relieving pain, and reducing blood pressure. According to traditional Chinese medicine, this point has the ability to harmonize liver energy and improve the circulation of vital energy throughout the body.

To better understand how acupuncture works in the brain, researchers have used modern neuroimaging techniques, especially functional magnetic resonance imaging (fMRI), which allows brain activity to be observed in real time.

This study represents the first systematic meta-analysis using the SDM (Seed-based d Mapping) technique to investigate how stimulation of the LR-3 point modifies brain activation patterns in healthy individuals. The researchers carried out a comprehensive search across eight scientific databases, in both English and Chinese, collecting studies that used functional magnetic resonance imaging to examine the effects of acupuncture at the LR-3 point. Only studies with healthy adult participants were included, which analyzed the immediate effects of acupuncture on brain activity and provided precise coordinates for the activated brain regions. In the end, ten high-quality studies were selected, involving 319 right-handed healthy participants.

The methodology used rigorous statistical analyses to identify which brain regions are consistently activated during LR-3 stimulation, in addition to examining factors such as needle retention time and the type of magnetic resonance imaging examination used.

The results revealed that acupuncture at the LR-3 point consistently activates four specific brain regions: the right postcentral gyrus, the left thalamus, the left middle frontal gyrus, and the right superior frontal gyrus. The right postcentral gyrus, which is part of the primary somatosensory cortex, is responsible for processing tactile, thermal, and painful sensations of the body. Its activation suggests that acupuncture at LR-3 directly influences brain systems involved in pain perception and modulation. The thalamus, a deep brain structure that acts as a relay station for information among different brain regions, was activated, which is significant given its crucial role in both acute pain perception and emotional processing.

A particularly interesting finding was that the longer the needle retention time, the greater the activation of the right superior frontal gyrus, a brain region closely related to emotional control and stress regulation. The left middle frontal gyrus, traditionally associated with language processing and cognitive functions, also showed consistent activation, suggesting that LR-3 stimulation may influence neural networks involved in cognitive processing.

For patients and healthcare providers, these findings provide important insights into the neurobiological mechanisms of acupuncture. The activation of brain regions related to pain processing provides a scientific basis for the clinical use of acupuncture in the treatment of painful conditions. The influence on emotional regulation areas suggests that LR-3 may be especially useful in the treatment of mood disorders such as depression and anxiety, corroborating its traditional use in Chinese medicine. The fact that longer acupuncture sessions intensify the activation of emotional control areas indicates that treatment duration may be an important factor to consider in therapeutic prescription.

For providers, these results suggest that acupuncture at LR-3 does not act only locally, but promotes changes in complex neural networks that include pain, emotion, and cognitive systems. This may explain why this point is traditionally considered so versatile in the treatment of different conditions.

The mapping of activated regions to functional brain networks revealed that acupuncture at LR-3 primarily influences six neural networks: the basal ganglia network, the auditory network, the left executive control network, the posterior salience network, the right executive control network, and the sensorimotor network. These networks are involved in functions such as motor control, emotional processing, attention, and decision-making. Subgroup analysis showed that studies using functional magnetic resonance imaging during stimulation (ts-fMRI) presented results more consistent with the main analysis than studies comparing true points with sham points (rs-fMRI), suggesting that the former approach may be more accurate for detecting acupuncture's specific effects.

Some important limitations must be considered when interpreting these results. First, the number of studies included was relatively small, and some had limited participant samples. In addition, all studies were performed in healthy people, so the results may not apply directly to patients with specific diseases. Differences in acupuncture techniques, neuroimaging data processing, and experimental designs across studies may also have influenced the results.

Some studies used unilateral LR-3 stimulation, while others used bilateral stimulation, which may produce differences in brain activation patterns. Future studies with larger samples and standardized methodologies will be needed to confirm and expand these findings. Research in patients with specific conditions such as chronic pain or depression will also be valuable for better understanding the therapeutic effects of acupuncture at LR-3.

In conclusion, this study provides solid scientific evidence that acupuncture at the LR-3 point produces specific and consistent changes in brain activity in healthy people, activating regions involved in pain processing, emotional regulation, and cognitive functions. The findings offer a neurobiological basis for understanding the therapeutic effects traditionally attributed to this acupuncture point and may guide future research and clinical practice in the field.

Strengths

  • 1First meta-analysis using the SDM technique for the LR-3 point
  • 2Robust sample with 319 participants from multiple studies
  • 3Rigorous analysis with control for bias and heterogeneity
  • 4Consistent identification of 4 activated brain regions
  • 5Mapping to known functional brain networks
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Limitations

  • 1Limited number of included studies (only 10)
  • 2Some studies used unilateral stimulation
  • 3Methodological variations across included studies
  • 4Studies conducted only in healthy individuals
  • 5Need for validation in patients with clinical conditions
Prof. Dr. Hong Jin Pai

Expert Commentary

Prof. Dr. Hong Jin Pai

PhD in Sciences, University of São Paulo

Clinical Relevance

The LR-3 point (Taichong, 太冲) occupies a central place in our everyday practice, employed across virtually the entire spectrum of conditions involving pain, emotional dysautonomia, and regulation of the liver axis according to classical patterns of Chinese medicine. This meta-analysis using the SDM technique, bringing together 319 healthy participants, confirms by neuroimaging what clinical practice has suggested for centuries: stimulation of LR-3 recruits the primary somatosensory cortex, the thalamus, and superior and middle frontal areas — precisely the regions that comprise the circuits of pain modulation and emotional regulation. For the physician who prescribes acupuncture in patients with chronic pain, anxiety or depressive disorders, or syndromes of sympathetic hyperactivity, this neurobiological substrate is no longer an inference but an objective data point. The significant correlation between longer needle retention time and greater activation of the right superior frontal gyrus has a direct implication for prescription: session duration is not a trivial parameter.

Notable Findings

Four brain regions emerged with robust statistical consistency: the right postcentral gyrus (Z=3.021), the left thalamus (Z=2.467), the left middle frontal gyrus (Z=2.49), and the right superior frontal gyrus (Z=2.086). The hierarchy of Z values deserves attention — the primary somatosensory cortex leads the activation, which mechanistically anchors the use of LR-3 as a first-line analgesic point. Even more revealing is the finding that needle retention time correlated significantly (p<0.00005) with activation of the superior frontal gyrus, a region linked to emotional control and stress processing. This suggests that for psychoemotional purposes, sessions with longer retention offer a measurable neurophysiological advantage. Mapping to six functional networks — including the salience network, executive control network, and sensorimotor network — broadens understanding of why this single point produces such clinically heterogeneous effects.

From My Experience

At the Pain Center of HC-FMUSP, LR-3 is rarely prescribed in isolation, but its presence in virtually all the protocols we have developed over decades reflects exactly what this work quantifies: it is a point of systemic action, not localized. I have observed that patients with chronic pain associated with a relevant emotional component — that profile of the tense, hypervigilant patient with low-back pain and poor sleep — respond particularly favorably to LR-3 when we combine it with ST-36 and CV-6; we usually note consistent subjective improvement starting in the third or fourth session. For maintenance, we typically work with cycles of eight to twelve sessions. As for needle retention time — the central finding of this article — our empirical practice already favored retention of 25 to 30 minutes in conditions with emotional predominance; we now have neurophysiological support for that choice. I do not indicate LR-3 as a main point in patients with severely deficient Qi without adequate support from tonifying points — the excessive dispersion that the point can promote worsens fatigue in those cases.

Specialist physician in Medical Acupuncture. Adjunct Professor at the Institute of Orthopedics, HC-FMUSP. Coordinator of the Acupuncture Group at the HC-FMUSP Pain Center.

Full original article

Read the full scientific study

Frontiers in Neuroscience · 2024

DOI: 10.3389/fnins.2024.1341567

Access original article

Scientific Review

Marcus Yu Bin Pai, MD, PhD

Marcus Yu Bin Pai, MD, PhD

CRM-SP: 158074 | RQE: 65523 · 65524 · 655241

PhD in Health Sciences, University of São Paulo. Board-certified in Pain Medicine, Physical Medicine and Rehabilitation, and Medical Acupuncture. Scientific review and curation of every entry in this library.

Learn more about the author →
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Medical disclaimer: This content is for educational purposes only and does not replace consultation, diagnosis, or treatment by a qualified professional. Some information may be assisted by artificial intelligence and is subject to inaccuracies. Always consult a physician.

Content reviewed by the medical team at CEIMEC — Integrated Centre for Chinese Medicine Studies, a reference in Medical Acupuncture for over 30 years.