What is the evidence‑based mechanism of action of acupuncture?

Evidence-Based Mechanisms of Acupuncture

Acupuncture works through multiple interconnected neurophysiological pathways: it activates peripheral afferent nerve fibers at acupoints that transmit signals through the spinal cord to brain centers, triggering release of endogenous opioids and neurotransmitters, modulating pain gating mechanisms in the spinal dorsal horn, reducing neuroinflammation, and regulating autonomic nervous system balance to restore homeostasis. 1, 2, 3

Peripheral Mechanisms at Acupoints

Nerve Fiber Activation

• Acupoints are excitable muscle/skin-nerve complexes containing high-density nerve endings that activate afferent fibers sending signals to the spinal cord. 1
• Manual acupuncture activates all fiber types (Aβ, Aδ, and C fibers), while electroacupuncture primarily activates Aβ and Aδ fibers. 3, 4
• At the muscle layer, A fiber threshold stimulation alone produces analgesia, but at the skin layer, C fiber threshold stimulation is required. 4
• The intensity and pattern of fiber activation determines the therapeutic effect—electroacupuncture activates A fibers while manual acupuncture activates both A and C fibers. 4

Local Biochemical Changes

• Acupuncture triggers ATP release from keratinocytes and subcutaneous mast cells, which is then broken down to adenosine in the extracellular space. 1
• Adenosine inhibits pain transmission through adenosine A1 receptor-dependent processes and simultaneously acts via P2X3 purinoceptor receptors for neuropathic pain relief. 1
• Acupuncture increases intracellular Ca²⁺ in mast cells, leading to ATP release that activates nerve cells and modulates pain-processing pathways. 1

Spinal Cord Mechanisms

Pain Gate Modulation

• Acupuncture activates spinal dorsal horn neurons through afferent fiber depolarization, modulating pain gating and inhibiting long-term potentiation (LTP) of wide dynamic range (WDR) neuronal activities. 4
• Electroacupuncture inhibits hyperphosphorylation of spinal cord NMDA receptors, preventing central sensitization in chronic pain. 2
• The number and size of active acupoints increase with pain severity, associated with enhanced neuronal responses in spinal dorsal horn neurons mediated by AMPA and NMDA receptors. 5

Neurotransmitter Release

• Acupuncture signals ascend through the spinal ventrolateral funiculus to brain centers, with signal molecules including opioid peptides (μ-, δ-, and κ-receptors), glutamate, serotonin, and cholecystokinin octapeptide. 3
• Electroacupuncture at 2 Hz produces enkephalin release while 100 Hz produces dynorphin release in the spinal cord—this frequency-dependent opioid release is critical for analgesia. 2, 3

Central Nervous System Mechanisms

Brain Network Activation

• A complex network of brain nuclei processes acupuncture signals, including the periaqueductal gray (PAG), nucleus raphe magnus (NRM), locus coeruleus, arcuate nucleus, amygdala, and hypothalamus. 3
• The Arc-PAG-NRM-spinal dorsal horn pathway plays a pivotal role in mediating acupuncture analgesia through opioid peptides and their receptors. 3
• Acupuncture modulates resting state functional connectivity in descending pain modulation and reward systems, with the amygdala serving as a key node linking these systems. 1

Neuroplasticity Changes

• After 4 weeks of acupuncture, patients show reduced primary somatosensory cortex gray matter volume and increased fractional anisotropy in adjacent white matter, correlating with improved tactile acuity. 1
• Acupuncture upregulates BDNF and its receptor TrkB, promoting synaptic plasticity and neuronal growth. 2
• Acupuncture regulates 5-HT receptor levels (particularly 5-HT1A receptors) in hippocampus CA1 region and modulates NMDAR subunit GluN2B expression. 2

Anti-Inflammatory Mechanisms

Neuroinflammation Reduction

• Electroacupuncture significantly reduces pro-inflammatory cytokines including IL-6, IL-1β, and TNF-α in both blood and hippocampus. 2
• Acupuncture inhibits microglial activation through the P2X7-NLRP3 inflammatory signaling pathway, particularly IL-1β-related microglial activation. 2
• For ischemic stroke, acupuncture modulates matrix metalloproteinase 2 (MMP2), aquaporin 4 and 9 expression, and inflammatory cell infiltration to provide neuroprotection. 1

Oxidative Stress Modulation

• Acupuncture decreases malondialdehyde levels and increases catalase, glutathione peroxidase, and superoxide dismutase activity in cerebral ischemia. 1
• These antioxidant effects contribute to reducing brain infarct volume and neurological deficits in stroke models. 1

Autonomic Nervous System Regulation

Sympathetic-Parasympathetic Balance

• Acupuncture activates sensory nerve fibers that project to autonomic nuclei in the brain (insular cortex, prefrontal cortex, anterior cingulate cortex, hypothalamus, PAG, nucleus tractus solitarius), which then modulate efferent autonomic nerves to restore homeostasis. 6
• Acupuncture alleviates visceral dysfunction and inflammation via efferent autonomic nerves, with the modulating pattern of sympathetic and parasympathetic nerves associated with specific acupoints and stimulation parameters. 6
• For irritable bowel syndrome, electroacupuncture decreases 5-HT, CGRP, and NPY levels in the gut-brain axis, restoring homeostasis. 2

Condition-Specific Mechanisms

Ischemic Stroke

• Acupuncture promotes neurogenesis by enhancing proliferation, migration, and differentiation of neural stem cells through down-regulation of RhoA/ROCK signaling and promoting GAP43 and BDNF expression. 1
• Commonly used acupoints for stroke (GV 20, ST 36, LI 11, GV 26, GV 14, LI 4) reduce post-stroke infarct volume and neurological deficits. 1

Chronic Pain

• For lower back pain, commonly used acupoints (BL 23, BL 25, BL 60, GB 30) stimulate relaxation of entrapped nerves and myofascia while improving local blood circulation. 1
• The analgesic effect involves both peripheral adenosine signaling and central opioid release mediated by the hypothalamic-pituitary-adrenal axis. 7

Clinical Implications and Caveats

Treatment parameters matter significantly: Most studies demonstrate effects with 15-30 minute sessions, once daily for 14-21 days. 2 The frequency of electroacupuncture determines which opioid peptides are released—2 Hz for enkephalin, 100 Hz for dynorphin. 2, 3

Individual variation exists: Individual differences in acupuncture analgesia are associated with inherited genetic factors and the density of cholecystokinin receptors, which antagonize acupuncture analgesia. 3

Acupoint specificity is dynamic: The number and size of active acupoints increase with disease severity, suggesting acupoints are not static but dynamically change according to pathological states. 5