Neuroscientific Update on the Mechanisms of Action of Acupuncture in Chronic Pain

This integrative review represents an important milestone in the scientific understanding of the mechanisms by which acupuncture produces analgesia in chronic pain conditions. Conducted by researchers from Hospital das Clínicas of USP, the analysis spans two decades of research (2000-2021) and offers a comprehensive neuroscientific perspective on this ancient technique.

The methodology employed a systematic search of the MEDLINE/PubMed, LILACS, and EMBASE databases, focusing on the central question regarding the possible mechanisms of acupuncture in the treatment of chronic pain. The authors organized the findings into two major categories: neural mechanisms and humoral/molecular mechanisms, providing a structured understanding of the processes involved.

The neural mechanisms proved to be complex and multifaceted. Acupuncture demonstrated the ability to stimulate all four types of somatic afferent fibers (Aα, Aβ, Aδ, and C), with fibers from groups 2, 3, and 4 appearing to be the primary mediators of analgesic effects. The technique produces three dimensions of perceptible effects: inhibition of nociceptive inputs resulting in analgesia, regulation of visceral function via somato-autonomic reflexes, and decreased skeletal muscle tone.

At the spinal cord level, multireceptive neurons of the dorsal horn play an essential role in acupuncture analgesia. Several neurotransmitters and protein kinases have been identified as mediators, including BDNF, GABA, serotonin, dopamine, norepinephrine, and opioid receptors. The brainstem emerges as a central regulator, with specific nuclei in the descending pain inhibition pathways being strongly associated with analgesic effects.

Neuroimaging studies, particularly with functional magnetic resonance imaging, have revolutionized the understanding of the cerebral effects of acupuncture. Research has revealed that the technique stimulates vast brain networks involving somatosensory, affective, and cognitive areas. It has been observed that acupuncture can reverse the abnormal neural plasticity associated with chronic pain, restoring normal patterns of brain connectivity.

Regarding humoral and molecular mechanisms, the endogenous opioid system remains the best-established mechanism. β-endorphin has been identified as the predominant peptide in acupuncture analgesia, while enkephalins appear to mediate other effects such as anxiolytic and antidepressant ones. Monoamines (serotonin, dopamine, and norepinephrine) have also demonstrated a crucial role, acting primarily through descending pain inhibition pathways.

Electroacupuncture has shown specific advantages due to the possibility of standardizing frequency, voltage, and waveform. Different frequencies produce distinct activation profiles: low frequency stimulates µ- and δ-opioid receptors and serotonergic pathways, while high frequency activates κ-opioid receptors. Recent studies have also identified the role of the endocannabinoid system in modulating analgesic effects.

The inhibition of microglial activation has emerged as another important mechanism, especially in neuropathic pain. Glial cells, including microglia and astrocytes, regulate neuronal homeostasis and participate in responses to injury. Acupuncture has demonstrated the ability to attenuate the activation of these cells, contributing to its analgesic effects.

Despite the significant advances, important limitations persist. Most of the knowledge derives from animal model studies, with limited translation to humans. Methodological challenges include difficulties with adequate blinding, lack of standardization of protocols, and absence of consensus regarding the best comparator for acupuncture. The variability in techniques among practitioners makes replication challenging.

The clinical implications are promising, suggesting that acupuncture represents a valid therapeutic strategy for various painful disorders through multiple neurobiological mechanisms. Knowledge of specific mechanisms may guide more effective and personalized protocols. Future research should focus on translating experimental findings to clinical applications, developing standardized protocols, and conducting studies that integrate multiple mechanisms simultaneously.