Acupuncture may play a key role in anti-depression through various mechanisms in depression
Li et al. · Chinese Medicine · 2024
Evidence Level
MODERATEOBJECTIVE
Review the distinct mechanisms of acupuncture in the treatment of depression across diverse targets and pathways
WHO
Animal models of depression including CUMS, CRS, LPS, post-stroke, and maternal separation
DURATION
Analysis of studies with multiple treatment durations
POINTS
GV-20, EX-HN3, ST-36, PC-6, LR-3, HT-7, BL-15, BL-18, BL-20, BL-23, CV-4, and others
🔬 Study Design
Narrative review
n=0
Analysis of multiple experimental studies
📊 Results in numbers
Mechanisms identified
Animal models reviewed
Acupuncture points analyzed
Signaling pathways studied
📊 Outcome Comparison
Efficacy by mechanism
This study shows that acupuncture acts against depression through multiple mechanisms in the brain and body. The research suggests that acupuncture may be a safe and effective alternative to traditional medications, with fewer side effects.
Article summary
Plain-language narrative summary
This comprehensive review analyzes the mechanisms by which acupuncture exerts antidepressant effects, drawing on extensive evidence from animal models of depression. Depression affects more than 264 million people worldwide and represents a significant challenge given the limitations of conventional pharmacological treatments, including adverse effects and inadequate response in many patients.
The methodology involved analysis of multiple animal models of depression, including chronic unpredictable mild stress (CUMS), chronic restraint stress (CRS), maternal separation (MS), lipopolysaccharide (LPS), post-stroke depression (PSD), and others. The most studied acupuncture points include GV-20 (Baihui), EX-HN3 (Yintang), ST-36 (Zusanli), PC-6 (Neiguan), LR-3 (Taichong), HT-7 (Shenmen), and back-shu points along the Bladder meridian such as BL-15, BL-18, BL-20, and BL-23.
The results identify eight major mechanisms through which acupuncture combats depression. First, regulation of central neurotransmitters, particularly serotonin (5-HT), norepinephrine (NE), and dopamine (DA), with studies showing that acupuncture increases 5-HT1A receptor expression and modulates serotonin transporter activity. Second, inhibition of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, with evidence that acupuncture lowers elevated cortisol and corticotropin-releasing hormone levels.
Third, enhancement of neuroplasticity through increased expression of brain-derived neurotrophic factor (BDNF) and its TrkB receptor, promoting neuronal growth and synapse formation. Fourth, inhibition of neuroinflammatory responses, reducing pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6, and modulating pathways including NF-κB/NLRP3.
Fifth, mediation of inhibition of the lateral habenular nucleus (LHb), a brain region critical in encoding aversive signals and depressive behavior. Sixth, improvement of oxidative stress and mitochondrial autophagy, protecting neurons against oxidative damage through regulation of factors such as Nrf2/HO-1.
Seventh, influence on epigenetic regulation, including changes in DNA methylation and histone modifications that affect gene expression related to depression. Eighth, regulation of the 'brain + X' axis, including the gut-brain, liver-brain, and spleen-brain axes, demonstrating that acupuncture addresses depression as a systemic disease.
The research also highlights important cellular signaling pathways, including MAPK (ERK, JNK), cAMP/PKA/CREB, Wnt/β-catenin, and others that mediate the antidepressant effects of acupuncture. Neuroimaging studies show that acupuncture modulates functional brain networks, including corticostriatal reward circuits and amygdala connectivity.
The clinical implications are significant, suggesting that acupuncture offers a multi-target therapeutic approach to depression, potentially complementing or serving as an alternative to pharmacological antidepressants. The therapy is particularly promising given its minimal side effects and capacity to address multiple aspects of depression pathophysiology simultaneously.
Limitations include the need for additional studies in primates, which more closely resemble human depression pathogenesis, and the need for high-quality randomized clinical trials to validate these mechanisms in humans. Future research should focus on translating these preclinical findings into clinical applications and refining treatment protocols.
Strengths
- 1Comprehensive review of multiple mechanisms of action
- 2Analysis of diverse validated animal models
- 3Consistent evidence across multiple signaling pathways
- 4Integration of neurobiological and behavioral findings
Limitations
- 1Based primarily on animal models
- 2Lack of primate studies
- 3Need for additional randomized clinical trials
- 4Variability in acupuncture protocols across studies
Expert Commentary
Dr. Marcus Yu Bin Pai
MD, PhD · Pain Medicine · Physical Medicine and Rehabilitation · Medical Acupuncture
▸ Clinical Relevance
Unipolar depression remains one of the most refractory disorders in the day-to-day work of the pain and rehabilitation clinic — and not by chance, since systemic inflammation, HPA axis dysfunction, and reduced BDNF are common denominators between chronic pain and depression. What this review offers the clinician is not a list of points but a mechanistic map that justifies acupuncture as a first-line adjunctive intervention in patients who already carry a psychiatric diagnosis associated with chronic pain syndrome. Populations with fibromyalgia, chronic low back pain, and central sensitization syndrome — which routinely respond poorly to antidepressants alone — are the most concrete candidates. The convergence between the pathways described (neuroinflammatory, HPA, BDNF-mediated neuroplasticity) and the pathophysiological substrate of chronic pain reinforces that we are not looking at two parallel problems but at a continuum that acupuncture can address transversally within the available multimodal armamentarium.
▸ Notable Findings
Among the eight mechanisms mapped, three deserve special attention from the physiatrist. Inhibition of lateral habenular nucleus hyperactivity — a structure that mediates the encoding of aversive signaling and behavioral defeat — is perhaps the most specific finding of this review, since it links a precise neuroanatomic target to clinically recognizable behaviors such as anhedonia and avoidance. Modulation of the NF-κB/NLRP3 pathway with reduction in IL-1β, TNF-α, and IL-6 maps directly onto the inflammatory model of depression, which has been gaining increasing traction in the chronic pain literature. And the gut-brain axis as a target of acupuncture opens a mechanistic window for patients with irritable bowel syndrome and comorbid depression — an extremely common profile in the clinic. The regulation of BDNF via TrkB receptors corroborates the neuroprotective role of the intervention in patients at risk for cognitive decline associated with long-standing depression.
▸ From My Experience
In my practice at the HC-FMUSP pain clinic, acupuncture is systematically included in the treatment plan for patients with moderate depression scores on the PHQ-9 associated with chronic pain, particularly when the psychiatrist has already tried two or more antidepressants without satisfactory response. I typically use GV-20, EX-HN3, and HT-7 as the foundation of the protocol, adjusting according to the predominant somatic component — ST-36 and PC-6 when there are digestive complaints or fatigue, and back-shu Bladder points when the pattern is more anxious and insomniac. The subjective response of mood improvement usually appears between the fourth and sixth session; before that, the patient frequently reports only improvement in sleep or physical disposition, which is already clinically relevant. On average, I work with cycles of twelve sessions before reassessing maintenance. I combine this with supervised aerobic exercise — whose synergy with BDNF is already documented in the literature — and maintain parallel psychiatric follow-up. The profile that responds best, in my experience, is the patient with depression reactive to chronic pain, no history of manic episodes, and good adherence to the multimodal plan.
Full original article
Read the full scientific study
Chinese Medicine · 2024
DOI: 10.1186/s13020-024-00990-2
Access original articleScientific Review
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 →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.
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