Acupuncture for Pain Management: Molecular Mechanisms of Action
Chen et al. · The American Journal of Chinese Medicine · 2020
Evidence Level
STRONGOBJECTIVE
Review the molecular and cellular mechanisms of acupuncture analgesia, from acupoints to the brain
WHO
Various animal models of pain (inflammatory, neuropathic, postoperative)
DURATION
Comprehensive review of decades of research
POINTS
ST-36, GB-20, LI-4, PC-6, GB-30, GB-34, among other traditional points
🔬 Study Design
Literature Review
n=0
Analysis of multiple studies on mechanisms of action
📊 Results in numbers
Electroacupuncture efficacy in pain
Reduction in pro-inflammatory cytokines
Glial cell inhibition
Opioid receptor activation
Percentage highlights
📊 Outcome Comparison
Activation of modulatory systems
This scientific review explains how acupuncture works in your body to relieve pain. Researchers found that acupuncture activates natural pain-relief systems in the brain and spinal cord, while also reducing inflammation. This helps explain why acupuncture is effective for various types of pain.
Article summary
Plain-language narrative summary
This comprehensive review examines the molecular mechanisms by which acupuncture produces analgesia, offering a modern scientific view of this long-standing Chinese therapy. The study analyzes the entire process from acupoint stimulation to brain responses, revealing how acupuncture modulates pain perception through multiple pathways. Acupoints have special anatomical structures, including mast cells, blood vessels, and nerve fibers, that make them more responsive to stimulation than non-acupoint points. When stimulated, these points generate specific sensations known as De Qi, considered fundamental to the therapeutic effect.
The research demonstrates that electroacupuncture is particularly effective, combining mechanical and electrical stimulation to produce analgesic effects superior to traditional manual acupuncture. In the spinal cord, electroacupuncture inhibits the activation of glial cells, including microglia and astrocytes, which are fundamental in maintaining chronic pain. This inhibition occurs through reduction of the chemokine CX3CL1 and increase in the anti-inflammatory cytokine interleukin-10, blocking the p38 MAPK and ERK pathways. Microglial inactivation mediates immediate analgesic effects, while astrocyte inactivation is responsible for long-term effects.
The descending pain modulatory system in the brain, including the anterior cingulate cortex, periaqueductal gray, and rostral ventromedial medulla, plays a crucial role in acupuncture analgesia. Multiple neurotransmitters are involved, including endogenous opioids, serotonin, norepinephrine, dopamine, GABA, and glutamate. Electroacupuncture frequency determines which opioid receptor types are activated: low frequency activates μ and δ receptors, while high frequency activates κ receptors. The study also introduces the 'Acupuncture+' strategy, proposing synergistic combinations with medications, stem cells, or techniques such as acupoint catgut embedding to optimize clinical outcomes.
This approach recognizes that, although acupuncture is effective alone, combining it with other therapies can produce superior results. The clinical implications are significant, providing a solid scientific basis for the use of acupuncture in pain management and guiding the development of more effective protocols. Understanding these mechanisms allows treatment personalization based on the specific molecular pathways involved in different types of pain.
Strengths
- 1Comprehensive review of molecular mechanisms
- 2Integration of preclinical and clinical research
- 3Analysis of multiple pathways of action
- 4Proposal of innovative therapeutic strategies
Limitations
- 1Based primarily on animal models
- 2Need for more clinical studies
- 3Variability across different types of pain
- 4Complexity of mechanisms not yet fully elucidated
Expert Commentary
Prof. Dr. Hong Jin Pai
PhD in Sciences, University of São Paulo
▸ Clinical Relevance
This review by Chen et al. consolidates decades of mechanistic research into a functional map that justifies technical choices in everyday outpatient practice. The distinction between electroacupuncture frequencies and their preferred opioid receptors—low frequency recruiting μ and δ receptors, high frequency recruiting κ receptors—has direct implications for parameter selection in different pain phenotypes: acute nociceptive pain responds differently from chronic neuropathic pain, and adjusting frequency becomes a grounded, not empirical, decision. The demonstration that microglial inhibition mediates immediate effects while astrocyte inactivation sustains long-term effects provides the physician with a model to explain to patients—and to himself—why benefit accumulates over a therapeutic cycle. Populations with chronic pain of high inflammatory burden, including chronic low back pain, fibromyalgia, and cancer pain, are those most benefited by this applied mechanistic understanding.
▸ Notable Findings
Two findings deserve special attention. First, the elucidation of the CX3CL1 and interleukin-10 pathway in glial modulation by electroacupuncture explains why the analgesic effect is neither instantaneous nor linear—the two- to fourteen-day window for glial cell inhibition corresponds, with remarkable coherence, to what is clinically observed as 'therapeutic latency period' in centralized chronic pain. Second, the proposal of the 'Acupuncture+' strategy represents a relevant conceptual shift: it moves away from the logic of acupuncture as monotherapy and into a model of synergistic combination with pharmacotherapy, stem cells, and complementary techniques such as catgut embedding. This aligns medical acupuncture practice with the multimodal paradigm that already guides contemporary chronic pain management, conferring on the technique a defined role within integrated protocols.
▸ From My Experience
In the Acupuncture Group of the Pain Center at HC-FMUSP, the frequency distinction in electroacupuncture has been part of routine protocol for years, but seeing this practice anchored in specific receptors strengthens the rationale for residents and for multiprofessional medical team discussions. I have observed that patients with chronic pain of central origin—central sensitization syndrome, moderate to severe fibromyalgia—rarely show response before the fourth or fifth session, which aligns perfectly with the astrocyte inhibition window described in this review. I usually plan initial cycles of eight to ten sessions before any efficacy judgment in these cases. For acute or subacute pain, response is typically perceived within the first two to three sessions. The 'Acupuncture+' concept is something I have practiced for some time, combining electroacupuncture with anti-inflammatories in acute phases or with dual antidepressants in chronic pain syndromes—this review provides the molecular basis for what was previously intuitive.
Full original article
Read the full scientific study
The American Journal of Chinese Medicine · 2020
DOI: 10.1142/S0192415X20500408
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