Pain as a Neural Phenomenon — and How Acupuncture Intercepts It
Pain is not simply a message that travels from injured tissue to the brain. It is a dynamic process of processing and modulation that unfolds at multiple levels of the nervous system — from peripheral nociceptors to the somatosensory cortex. At each level, endogenous inhibitory mechanisms can be activated. Medical acupuncture operates on exactly these mechanisms.
Two conceptual pillars underpin acupuncture analgesia: the gate control theory of pain, proposed by Melzack and Wall in 1965, and the endogenous opioid and monoaminergic systems, the mechanisms of which were elucidated by the work of Ji-Sheng Han starting in the 1970s. Together, these models explain how the insertion of a needle — a relatively simple mechanical stimulus — produces analgesia of clinically meaningful magnitude and duration.
Gate Control Theory of Pain
In 1965, Ronald Melzack and Patrick Wall published one of the most influential papers in medical neuroscience: the gate control theory of pain. The model proposes that pain-signal transmission in the spinal cord can be modulated — amplified or suppressed — by a "gate" in the dorsal horn.
The gate is controlled by the balance between two types of afferent fibers: large myelinated fibers (A-beta and A-delta), which carry touch, pressure, and rapid pain, and small unmyelinated fibers (C), which carry slow, diffuse pain. When large fibers are predominantly activated, inhibitory interneurons in the dorsal horn suppress C-fiber signals to the brain — the gate "closes". When C fibers predominate (tissue injury, chronic inflammation), the gate "opens" and pain is amplified.
Peripheral painful stimulus
C fibers (chronic, diffuse pain) and A-delta fibers (acute, localized pain) carry nociceptive signals to the dorsal horn of the spinal cord — Rexed laminae I, II, and V.
Insertion of the acupuncture needle
At the acupuncture point, the needle preferentially activates A-delta and A-beta fibers — large fibers that carry touch, pressure, and the deqi sensation. This signal reaches the dorsal horn at the same time as the nociceptive signal.
Inhibition by GABAergic interneurons
Large-fiber activation stimulates inhibitory interneurons (using GABA and enkephalins) in the substantia gelatinosa of the dorsal horn, which suppress nociceptive transmission from C fibers to the second-order neuron.
Gate closure — pain reduction
With the gate "closed" by presynaptic inhibition, fewer pain signals reach the thalamus and somatosensory cortex. The patient perceives reduced pain while the needle is inserted and for a variable period after its removal.
Endogenous Opioids: The Body's Internal Morphine
The endogenous opioid system is the body's most potent natural analgesic system. Composed of three families of peptides — beta-endorphins, enkephalins, and dynorphins — this system acts on mu, delta, and kappa receptors distributed throughout the central and peripheral nervous system.
Pioneering work by Ji-Sheng Han at Peking University showed that acupuncture releases these peptides in specific ways depending on the stimulation frequency. Studies with the opioid antagonist naloxone confirmed this finding: when given before the acupuncture session, the analgesic effect is significantly reduced — direct proof that the opioid pathway is a central mediator of acupuncture analgesia.
Beyond opioids, acupuncture modulates monoaminergic neurotransmitters: serotonin (5-HT) and norepinephrine are released by descending inhibitory pathways from the brainstem. These neurotransmitters act in the dorsal horn to enhance suppression of nociceptive transmission — the same mechanism exploited by tricyclic antidepressants and SNRIs in chronic pain treatment.
| ENDOGENOUS OPIOID | MAIN RECEPTOR | RELEASED BY | MAIN EFFECT |
|---|---|---|---|
| Beta-endorphin | Mu (μ) | Acupuncture 2 Hz — hypothalamus/pituitary | Intense systemic analgesia, mild euphoria |
| Enkephalin | Delta (δ) | Acupuncture 2 Hz — spinal dorsal horn | Segmental analgesia, spinal modulation |
| Dynorphin | Kappa (κ) | Acupuncture 100 Hz — spinal cord | Spinal analgesia, modulation of neuropathic pain |
| Met-enkephalin | Delta (δ) | Acupuncture 2-15 Hz | Modulation of nociceptive transmission |
DNIC: The "Pain Inhibits Pain" Mechanism
Beyond the spinal gates and endogenous opioids, there is a third central mechanism in acupuncture analgesia: diffuse noxious inhibitory controls (DNIC). DNIC is the neurophysiologic basis of the popular phenomenon that "one pain relieves another pain".
The mechanism involves the nucleus of the solitary tract and the brainstem reticular formation: when a nociceptive stimulus is applied to a body area distant from the original pain, on-off neurons in the brainstem activate descending inhibitory pathways that suppress pain throughout the body. Needling at distal points — a classic acupuncture technique — can tap into exactly this mechanism.
Experimental Confirmation of the Mechanisms
These mechanisms are not merely theoretical. Decades of experimental research converge on a robust body of evidence that confirms them directly:
- Han (1980): injecting CSF from acupuncture-treated rats into naive rats produced analgesia — proof that analgesic substances are released in the central nervous system.
- Naloxone studies: the opioid antagonist reverses 40-60% of acupuncture analgesia, confirming that the opioid pathway is a mediator — but not the only one.
- fMRI in humans: acupuncture at ST36 modulates activity in the insular cortex, anterior cingulate cortex, and periaqueductal gray matter — central pain-modulation circuits.
- PET-scan with opioid ligands: acupuncture increases mu-opioid receptor binding in brain regions involved in analgesia and emotional regulation.
- Microdialysis studies: enkephalin and beta-endorphin levels in cerebrospinal fluid increase significantly after an acupuncture session.
Frequently Asked Questions
Frequently Asked Questions
The immediate effect (during the session) is mediated by spinal gates and lasts as long as the needle is in place. Endogenous opioid release produces analgesia that may last hours to days. With repeated sessions, the resulting neuroplasticity can produce cumulative improvement over weeks to months, especially in chronic pain.
Studies show that about 20-25% of patients are "non-responders". This may be related to genetic polymorphisms in the opioid and serotonergic systems, advanced central sensitization (severe fibromyalgia), chronic opioid use (which desensitizes endogenous receptors), or the presence of pain predominantly of visceral or oncologic origin, where peripheral mechanisms are dominant.
Acupuncture does not replace analgesics in severe acute pain. Its most established clinical role is in treating chronic pain — where systematic reviews describe clinical benefit for conditions such as chronic low back pain and headaches, with a favorable adverse-event profile when performed by a trained physician. Acupuncture is typically integrated with, not a substitute for, conventional pharmacotherapy — the best combination is decided by the physician case by case.
Deqi — the sensation of heaviness, pressure, or warmth around the needle — indicates activation of A-delta fibers and is correlated with greater analgesic response in studies. However, effects can occur even without intense deqi. Trained physicians adjust the technique to obtain an adequate response, respecting the patient's comfort threshold.