Neurophysiological Basis of Acupuncture-Induced Analgesia: An Updated Review

This comprehensive review examines the neurophysiologic foundations of acupuncture-induced analgesia, consolidating decades of scientific research to explain how this ancient therapeutic modality produces pain relief through well-defined biomedical mechanisms. Acupuncture, with origins that go back 10,000 years BCE in China, involves the insertion of needles at specific points on the body to achieve therapeutic effects. According to Traditional Chinese Medicine, acupuncture modulates the flow of Qi 氣 and Xue 血 through the meridians to re-establish homeostasis of the principal organs, governed by the laws of Yin-Yang 陰陽 and the Five Elements 五行. The study reveals that acupuncture points are anatomically distinct sites, characterized by higher density of innervation, more compact connective tissue, and elevated concentrations of TRPV1 receptors.

Research demonstrates that 18% more force is required to remove a needle from an acupoint compared with control points, suggesting differentiated tissue organization. The 365 principal points are distributed along 12 meridians that cover the entire body. The review presents evidence that different frequencies of electroacupuncture activate distinct neurotransmitter systems: 2 Hz primarily stimulates myelinated A-beta fibers and releases enkephalins, beta-endorphins, and endomorphins, whereas 100 Hz activates smaller A-delta and C fibers, selectively releasing dynorphins. The De-Qi 得氣 phenomenon, described as a sensation of pressure or dull ache during treatment, is fundamental for analgesic efficacy.

Functional neuroimaging studies demonstrate that De-Qi activates anticorrelated brain networks, including deactivation of the default mode network and activation of somatosensory regions. Acupuncture analgesia operates through multiple integrated neurobiologic mechanisms. First, needle insertion at acupoints activates mechanoreceptors, sending afferent signals through ventrolateral tracts to brain nuclei that modulate pain perception via descending inhibitory pathways. Second, there is release of endogenous opioid peptides that act on mu-opioid and N/OFQ receptors, demonstrated by positron emission tomography studies showing increased opioid receptor binding in the cingulate cortex, caudate nucleus, and amygdala.

Third, there is modulation of the noradrenergic and serotonergic systems, with evidence that alpha-2 adrenergic receptors suppress nociceptive signaling while alpha-1 receptors facilitate it. The serotonergic system also participates, with 5-HT1A and 5-HT3 receptors mediating analgesia. Fourth, acupuncture modulates the glutamatergic NMDA/AMPA/kainate system, crucial in spinal nociception processing and central sensitization. Studies show that NMDA receptor blockers potentiate the analgesic effects of electroacupuncture.

Fifth, inflammatory mediators produced by local microtrauma from the needle stimulate unmyelinated C fibers, activating diffuse noxious inhibitory control (DNIC), which enhances the general descending inhibitory control of nociception. Sixth, with repeated treatments, neural plasticity develops in the spinal dorsal horn through the interaction between long-term potentiation and depression of C-fiber potentials, providing lasting relief. The review also addresses the phenomenon of nonresponsiveness to acupuncture, present in approximately one in seven patients. Research has identified that nonresponders show greater expression of cholecystokinin octapeptide (CCK-8) and its receptors in the hypothalamus, a substance with anti-opioid activity that antagonizes electroacupuncture analgesia.

Clinical studies support these mechanisms, demonstrating reduced demand for opioid medications in chronic pain patients treated with electroacupuncture, in addition to proven efficacy in postoperative pain control across several surgical specialties. The clinical implications are significant, as this mechanistic understanding provides a solid scientific basis for the use of acupuncture in pain management, facilitating its integration into conventional medicine and the optimization of treatment protocols.