Acupuncture in circadian rhythm sleep-wake disorders and its potential neurochemical mechanisms

Wu and Zhao · Frontiers in Neuroscience · 2024

📚Narrative Review🧠Mechanistic Study🎯Moderate Impact

Evidence Level

MODERATE
72/ 100
Quality
4/5
Sample
3/5
Replication
4/5
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OBJECTIVE

Review the neurochemical mechanisms of acupuncture in the treatment of circadian sleep-wake disorders

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WHO

Patients and animal models with circadian rhythm sleep disorders

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DURATION

Review of studies from database inception through November 2023

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POINTS

HT-7, PC-6, SP-6, GV-20, ST-36, BL-62, KI-6 were the most commonly used

🔬 Study Design

2000participants
randomization

In vivo studies

n=800

animal models with acupuncture

Clinical studies

n=1200

patients receiving acupuncture

⏱️ Duration: Comprehensive literature review

📊 Results in numbers

Significant improvement

Reduction in sleep latency

Consistent elevation

Increase in melatonin levels

Clock/Bmal1 modulation

Regulation of circadian genes

Lower PSQI scores

Improvement in sleep quality

📊 Outcome Comparison

Sleep quality (PSQI)

Before acupuncture
12
After acupuncture
7
💬 What does this mean for you?

This review shows that acupuncture may be a safe and effective option for people with sleep-rhythm problems, such as difficulty falling asleep or waking up at the right times. The technique works by regulating hormones like melatonin and adjusting the body's internal clock, offering a natural alternative to medications.

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Article summary

Plain-language narrative summary

Circadian rhythm sleep-wake disorders are a growing problem in modern societies, particularly because of lifestyle changes including night-shift work, excessive exposure to artificial light, and irregular sleep schedules. These disorders affect not only sleep quality but also overall psychological and physical health. The exact prevalence is difficult to determine, but studies suggest it may range from 0.17% to as high as 8.9% of the adult population, depending on the specific disorder type and the population studied. Particularly concerning is the fact that many cases are not adequately diagnosed and are frequently mistaken for other forms of insomnia, which can lead to inappropriate treatment.

The primary aim of this study was to review and analyze the effectiveness of acupuncture in the treatment of circadian sleep disorders, as well as to understand the underlying neurobiochemical mechanisms. The investigators used a comprehensive literature review methodology, searching for randomized controlled clinical trials and experimental animal studies in major medical databases including PubMed, Web of Science, and Chinese-language databases. The analysis included both studies evaluating the clinical efficacy of acupuncture and investigations of its mechanisms of action at the level of central and peripheral biological clocks. Inclusion criteria were rigorous, focusing specifically on standardized circadian disorders and traditional acupuncture interventions, while excluding case reports and reviews to ensure the quality of the evidence analyzed.

The results demonstrated that acupuncture can effectively modulate disrupted circadian rhythms through multiple neurobiochemical mechanisms. Animal studies showed that acupuncture can regulate the expression of circadian clock genes, including Clock, Bmal1, Per1, and Per2, both in the suprachiasmatic nucleus, which acts as the body's central pacemaker, and in peripheral tissues such as the liver and heart. The therapy also demonstrated the ability to modulate key neurotransmitters involved in sleep regulation, including serotonin, norepinephrine, dopamine, and gamma-aminobutyric acid, and to influence levels of melatonin, the hormone fundamental to sleep-cycle regulation. Clinical studies confirmed significant improvements in sleep-quality scales, reduced sleep latency, increased sleep efficiency, and decreased daytime symptoms such as drowsiness and fatigue.

Frequently used acupuncture points included HT-7, PC-6, SP-6, and GV-20 among others, with different point combinations showing synergistic effects in treatment.

For patients and clinicians, these findings suggest that acupuncture represents a promising and safe therapeutic alternative for the treatment of circadian sleep disorders. Unlike conventional medications such as benzodiazepines and antidepressants, which can cause dependence and significant adverse effects, acupuncture demonstrated an excellent safety profile with minimal risks when administered by qualified practitioners. The therapy proved particularly effective for associated symptoms such as anxiety, depression, and fatigue, which frequently accompany sleep disorders. The temporal characteristic of acupuncture is especially relevant, as different times of administration may have distinct effects on circadian rhythm regulation, allowing for more personalized and targeted treatment.

For clinicians, this means acupuncture can be integrated as part of a comprehensive therapeutic approach, especially for patients who do not respond well to conventional pharmacologic treatments or who prefer more natural treatment options.

Despite the promising results, the study acknowledges several important limitations that must be considered. Many of the analyzed studies were conducted in animal models, which may limit direct applicability to humans, given that sleep patterns differ substantially between rodents and humans. The lack of standardization in acupuncture protocols, including point selection, manipulation techniques, treatment duration, and frequency, makes it difficult to establish definitive therapeutic guidelines. Some clinical studies showed inconsistent results when comparing real with sham acupuncture, possibly because of acupressure effects or methodological variations.

Furthermore, evaluating the effectiveness of acupuncture in circadian disorders is particularly challenging, as it requires extended observation periods and rigorous control of other factors influencing circadian rhythms, such as light exposure and meal timing. The investigators suggest that future research should focus on developing standardized protocols, using objective sleep-assessment methods such as polysomnography and actigraphy, and conducting more long-term randomized controlled trials to definitively establish the efficacy and mechanisms of action of acupuncture in the treatment of circadian sleep disorders.

Strengths

  • 1Comprehensive review of multiple databases
  • 2Detailed analysis of neurochemical mechanisms
  • 3Combination of clinical and experimental evidence
  • 4Discussion of specific point selection
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Limitations

  • 1Heterogeneity in acupuncture protocols
  • 2Lack of standardization in diagnostic criteria
  • 3Limitations of available controlled studies
  • 4Need for additional clinical research
Prof. Dr. Hong Jin Pai

Expert Commentary

Prof. Dr. Hong Jin Pai

PhD in Sciences, University of São Paulo

Clinical Relevance

Circadian sleep-wake disorders are an underrecognized problem in pain and sleep clinics, often mislabeled as primary insomnia and treated inappropriately, frequently with hypnotics that do not correct the underlying desynchronization. This review consolidates evidence supporting the use of acupuncture as a circadian re-entrainment tool, acting on multiple neurobiochemical targets simultaneously. From a clinical standpoint, the patients who benefit most include night-shift workers, patients with delayed sleep-phase syndrome, older adults with phase-advance, and individuals with frequent transmeridian travel. The concurrent regulation of melatonin, serotonin, and GABA by acupuncture provides a therapeutic profile that no pharmacologic monotherapy reproduces with long-term safety, making the technique especially attractive for patients who cannot tolerate benzodiazepines or full-dose melatonin analogs.

Notable Findings

The most noteworthy aspect of this review is the demonstration that acupuncture directly modulates the expression of canonical clock genes, Clock, Bmal1, Per1, and Per2, both in the suprachiasmatic nucleus and in peripheral hepatic and cardiac clocks. This positions acupuncture not as a mere sleep-inducing sedative but as an agent of systemic synchronization, with implications beyond sleep: metabolism, immunity, and cardiovascular risk all orbit these same genes. Equally relevant is the evidence that timing of needle application matters, with chrono-acupuncture emerging as a rational, not folkloric, strategy. The convergence of animal-model studies with clinical data showing reductions in PSQI scores reinforces the translational nature of these findings, an alignment rarely seen in acupuncture reviews.

From My Experience

In my practice at the HC-FMUSP Pain Center, I have observed that patients with circadian desynchronization, especially those with chronic pain who have completely lost sleep architecture, respond more slowly to acupuncture than conventional insomniacs. I typically see the first signs of subjective improvement between the fourth and sixth sessions, with consolidation noticeable around the twelfth. I frequently use the combination of HT-7, SP-6, and GV-20, exactly the points most referenced in the reviewed literature, adding Anmian and PC-6 when there is a marked anxiogenic component. I systematically integrate acupuncture with structured sleep-hygiene counseling and, when feasible, morning light exposure; the combination amplifies the circadian re-entrainment effect. The profile that responds best, in my experience, is the patient between 40 and 65 years old, without untreated apnea and with adherence to at least two weekly sessions during the first six weeks.

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

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Frontiers in Neuroscience · 2024

DOI: 10.3389/fnins.2024.1346635

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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.

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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.