“Neuroinflammation refers to a regulated immune response within the central nervous system (CNS), triggered by diverse insults such as traumatic injury, infections, metabolic dysfunction, or dysbiosis.” [1,2]. This process involves interactions between neural and immune systems and is increasingly recognized as a key factor in the onset and progression of numerous neurological and neurodegenerative conditions. Chronic neuroinflammation has been particularly linked to diseases such as Alzheimer's, Parkinson's, major depressive disorder, and multiple sclerosis, where it contributes to ongoing neural damage and hinders repair mechanisms [3].

This immune response typically involves the coordinated activation of glial cells—especially microglia and astrocytes—and the secretion of pro-inflammatory cytokines, including interleukin-1β, tumor necrosis factor-α, and interleukin-6 [4]. It is often accompanied by a breakdown of the blood–brain barrier (BBB), which permits peripheral immune molecules to enter the CNS and intensify inflammatory signaling [5]. These events disrupt the balance of neuronal function, playing a role in both short-term and long-term neural impairment. While experimental therapies targeting cytokines and immune pathways have demonstrated promising results in animal models, their clinical effectiveness is still constrained by issues such as poor BBB penetration, systemic side effects, and difficulties in precisely modulating inflammation within the CNS [6,7].

Electroacupuncture (EA), which combines traditional acupuncture with targeted electrical stimulation, has garnered growing interest as a neuromodulatory intervention capable of influencing neuroimmune dynamics [8]. Unlike conventional pharmacotherapies, EA exerts its effects through the excitation of defined peripheral sensory pathways, initiating a cascade of neural signaling that converges on key central autonomic and limbic networks [9]. This coordinated neural activity appears to modulate immune responses both centrally and peripherally, likely through reflex circuits involving the vagus nerve and other autonomic efferents [8,9].

In this review, we explore the mechanistic basis by which EA may modulate neuroinflammatory processes across defined neural circuits. We focus on three key components of this neuromodulatory pathway: the activation of somatosensory afferents, the central integration of sensory input within autonomic and limbic structures, and the downstream engagement of efferent mechanisms that influence peripheral immune responses. In addition, we consider how these pathways may intersect with pharmacological therapies, offering insights into potential synergistic strategies that could enhance therapeutic efficacy in chronic neuroinflammatory conditions. This integrative perspective may promote the development of future translational approaches within the field of bioelectronic medicine.a