Effect of Acupuncture on BDNF Signaling Pathways in Several Nervous System Diseases
Miao et al. · Frontiers in Neurology · 2023
Evidence Level
MODERATEOBJECTIVE
Review how acupuncture modulates BDNF signaling pathways in the treatment of neurological diseases
WHO
Animal models with neuropathic pain, Parkinson disease, cerebral ischemia, depression, and spinal cord injury
DURATION
Review of studies published through 2023
POINTS
Several points including Baihui (GV-20, 百會), Yanglingquan (GB-34, 陽陵泉), Zusanli (ST-36, 足三里)
🔬 Study Design
Narrative Review
n=0
Analysis of studies on acupuncture and BDNF
📊 Results in numbers
Dual regulation of BDNF
Neurological diseases studied
Signaling pathways identified
📊 Outcome Comparison
Effect on BDNF expression
This study shows that acupuncture works in the brain through an important protein called BDNF, which helps neurons communicate better. Acupuncture can either increase or decrease this protein depending on the condition being treated, promoting neurological recovery.
Article summary
Plain-language narrative summary
This comprehensive review examines how acupuncture modulates brain-derived neurotrophic factor (BDNF) and its signaling pathways in the treatment of various neurological diseases. BDNF is an essential protein that regulates synaptic plasticity, neuronal development, and cell survival in the central nervous system. The authors demonstrate that acupuncture exerts a dual regulatory function on BDNF pathways, being able to activate or inhibit different signaling cascades depending on the neurological condition treated. In neuropathic pain, electroacupuncture significantly reduces BDNF and TrkB levels in the dorsal horn of the spinal cord, blocking central sensitization mediated by the BDNF/TrkB pathway.
This inhibitory effect is crucial for reducing the hyperalgesia and allodynia characteristic of chronic neuropathic pain. In contrast, for conditions such as Parkinson disease, cerebral ischemia, depression, and spinal cord injury, acupuncture promotes neuroprotection and functional recovery through upregulation of BDNF and activation of downstream pathways such as PI3K/Akt and MEK/ERK. In Parkinson disease, electroacupuncture at points such as Yanglingquan (GB-34) and Taichong (LR-3) increases BDNF levels in the substantia nigra, promoting the survival of dopaminergic neurons and improving motor symptoms. For cerebral ischemia, acupuncture treatment at Baihui (GV-20) and Dazhui (GV-14) increases BDNF expression, providing BDNF-mediated neuroprotection and preventing neuronal apoptosis through the Raf-1/MEK1/2/ERK1/2 cascade.
In depression, electroacupuncture restores hippocampal synaptic plasticity through activation of the tPA/BDNF pathway, promoting antidepressant effects. The proposed mechanisms include acupuncture's ability to stimulate the synthesis and release of neurotrophic factors, regulate endogenous neurogenesis, modulate structural and functional synaptic plasticity, and influence the activity of glial cells such as astrocytes and microglia. The review highlights that different acupoints and stimulation parameters may specifically influence certain molecular pathways, suggesting a personalized approach to different neurological conditions. Limitations include the predominance of preclinical studies and the need for more controlled clinical trials to validate these mechanisms in humans.
Strengths
- 1Comprehensive review of multiple neurological conditions
- 2Detailed analysis of molecular mechanisms
- 3Identification of dual regulation of BDNF by acupuncture
- 4Strong theoretical grounding on signaling pathways
Limitations
- 1Predominance of preclinical studies
- 2Lack of standardization in acupuncture protocols
- 3Need for more controlled clinical trials
- 4Limited exploration of the pro-BDNF/p75NTR pathway
Expert Commentary
Prof. Dr. Hong Jin Pai
PhD in Sciences, University of São Paulo
▸ Clinical Relevance
BDNF modulation by acupuncture represents one of the most solid neurochemical foundations justifying its use in neurological diseases that are difficult to manage. What this review articulates clearly is that this is not a unidirectional effect: acupuncture both elevates and suppresses BDNF/TrkB signaling depending on the pathophysiological context. This has direct clinical implications — the same therapeutic toolset serves neuropathic pain, where spinal downregulation of BDNF is desirable, and stroke or Parkinson disease, where neuroprotection through upregulation is the target. For neurologists and rehabilitation physicians, this work provides mechanistic grounding to integrate acupuncture into post-stroke recovery protocols, symptomatic management of Parkinson disease, and adjuvant treatment of refractory depression — populations in which pharmacological resources frequently prove insufficient.
▸ Notable Findings
Dual regulation of BDNF is the central finding and deserves careful attention. In neuropathic pain, electroacupuncture reduces BDNF and TrkB in the dorsal horn of the spinal cord, interrupting the central sensitization cycle that sustains hyperalgesia and allodynia — a mechanism that explains clinical results often exceeding those obtained with gabapentinoids alone. At the opposite pole, points such as Yanglingquan (GB-34) and Taichong (LR-3) elevate BDNF in the substantia nigra and protect dopaminergic neurons in the parkinsonian model, while Baihui (GV-20) and Dazhui (GV-14) activate the Raf-1/MEK1/2/ERK1/2 cascade after cerebral ischemia, reducing apoptosis. The tPA/BDNF pathway in the hippocampus as the antidepressant mechanism of electroacupuncture connects this therapy to contemporary depression neurobiology, particularly relevant in patients who do not tolerate serotonergic antidepressants.
▸ From My Experience
In my practice at the Pain Center of HC-FMUSP, understanding that acupuncture modulates BDNF bidirectionally confirms something we have observed empirically for decades: the same point acts differently depending on the state of the patient's nervous system. In peripheral neuropathic pain, I typically see consistent analgesic response between the third and fifth electroacupuncture session, especially when combined with low-dose amitriptyline and desensitizing physical therapy. In patients with post-stroke motor sequelae, the response profile is slower — perceptible functional improvement usually emerges between the sixth and tenth session, and we typically work with cycles of 15 to 20 sessions before reassessing. In mild to moderate Parkinson disease, we combine acupuncture with motor rehabilitation and observe improvement in rigidity and resting tremor that goes beyond what physical therapy achieves alone. The patient who responds best is one with a recent diagnosis, not yet on polypharmacy, and with good cognitive reserve to adhere to the protocol.
Full original article
Read the full scientific study
Frontiers in Neurology · 2023
DOI: 10.3389/fneur.2023.1248348
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.
Related articles
Based on this article’s categories