What is the mechanism of electrical acupuncture?

Mechanisms of Electrical Acupuncture

Electroacupuncture (EA) operates through multiple interconnected biological pathways, primarily involving frequency-dependent release of endogenous opioid peptides, modulation of neurotransmitters in the central nervous system, reduction of neuroinflammation, and restoration of synaptic plasticity in key brain regions. 1

Frequency-Dependent Opioid Release

The therapeutic effects of EA are fundamentally determined by stimulation frequency, with distinct neuropeptide profiles released at different frequencies:

• Low frequency EA (2 Hz) accelerates the release of enkephalin, beta-endorphin, and endomorphin 2
• High frequency EA (100 Hz) selectively increases dynorphin release 2
• Combined frequencies (2-100 Hz) produce simultaneous release of all four opioid peptides, resulting in maximal therapeutic effect 2
• This frequency-dependent mechanism has been clinically verified in patients with chronic low back pain and diabetic neuropathic pain 2

Neuroinflammation Modulation

EA significantly reduces inflammatory processes in both peripheral and central nervous systems:

• Downregulates pro-inflammatory cytokines including IL-6, IL-1β, and TNF-α in both blood and hippocampus 1
• Inhibits microglial activation through the P2X7-NLRP3 inflammatory signaling pathway, particularly IL-1β-related microglial activation 1
• Prevents over-activation of indoleamine 2,3-dioxygenase (IDO), a key enzyme in tryptophan degradation along the kynurenine pathway that links inflammation to depression 1
• Reduces peripheral inflammation by acting on the hypothalamic-pituitary-adrenal (HPA) axis, mediating peripheral opioid release and decreasing COX-2 and PGE2 levels 3

Hippocampal Synaptic Plasticity Restoration

EA restores structural and functional changes in the hippocampus through multiple pathways:

Serotonin System Modulation

• Regulates 5-HT receptor levels (particularly 5-HT1A receptors) in hippocampus CA1 region, restoring synaptic plasticity 1
• Promotes expression of 5-HT1A receptor mRNA and protein, improving hippocampal synaptic function 1

Glutamate Receptor Regulation

• Modulates NMDAR subunit GluN2B expression and enhances long-term potentiation (LTP) in the hippocampus 1
• Operates through the GluN2B/CaMKII/CREB signaling pathway, alleviating depression-like behavior and improving hippocampal plasticity 1
• Increases expression of synaptic proteins including MAP-2, PSD-95, and synaptophysin (SYN) 1

Neurotrophic Factor Enhancement

• Upregulates BDNF and its receptor TrkB, promoting synaptic plasticity and neuronal growth 1
• BDNF acts as a transducer linking EA treatment to neuroplastic changes that alleviate symptoms 1

Spinal Cord Mechanisms

EA modulates pain transmission at the spinal level through several pathways:

• Reduces spinal N-methyl-D-aspartate receptor subunit GluN1 phosphorylation through serotonin and norepinephrine release 4
• Inhibits hyperphosphorylation of spinal cord NMDAR, preventing central sensitization in chronic pain conditions 1
• Desensitizes peripheral nociceptors and reduces proinflammatory cytokines both peripherally and in the spinal cord through opioid mechanisms 4

Peripheral Mechanisms

At the acupoint level, EA initiates local biochemical changes:

• Activates ATP and TRPV channels at the acupoint area, initiating the therapeutic cascade 3
• Stimulates a larger area than traditional acupuncture, providing more reproducible and objective effects 5
• Peripheral opioid release is mediated through HPA axis modulation 3

Gut-Brain Axis Modulation (for visceral conditions)

EA restores balance in the gut-brain axis through:

• Decreases levels of 5-HT, CGRP, and NPY in the gut-brain axis, restoring homeostasis in irritable bowel syndrome 1
• Modulates the enteric nervous system and affects gut motility through neurotransmitter regulation 1

Clinical Implications

The frequency-specific nature of EA is critical for clinical application:

• For inflammatory and neuropathic pain: 2-10 Hz is more effective than 100 Hz 4
• For maximal opioid release: Combined 2 Hz and 100 Hz frequencies produce optimal results 2
• Treatment duration: Most studies demonstrate effects with 15-30 minute sessions, once daily for 14-21 days 1

Important caveat: While these mechanisms are well-documented in preclinical models, the exact molecular pathways and their relative contributions in human clinical conditions require further investigation 5. The mechanisms involve complex neuro-immune networks at multiple levels—peripheral, spinal, and supraspinal—making EA a multi-targeted intervention rather than a single-pathway treatment 6.