The Neuro-Vascular-Immune (NVI) functional unit: A proposed framework for understanding acupuncture action

Acupuncture has demonstrated consistent clinical efficacy in treating pain, autonomic dysfunction, and immune-mediated disorders, yet its integration into mainstream evidence-based medicine remains limited by the absence of a unified, anatomically defined mechanism of action. To address this gap, we propose the neuro-vascular-immune (NVI) functional unit as a hypothetical framework to understand the structural and functional substrate underlying acupoints. This specialized perivascular microdomain, enriched in sensory nerve endings, perivascular mast cells, and immune-stromal elements, acts as a mechanosensitive interface transducing physical stimuli into biological signals. Our model suggests that acupuncture exerts its effects primarily through targeted mechanical activation of these NVI units, converting local physical inputs into coordinated regional and systemic neuro-immune responses. Mast cells within the NVI unit are proposed to function as central signal integrators, mediating context-dependent modulation of innate immunity, adaptive immune polarization, and tissue microenvironments. This framework aims to complement traditional meridian theory by providing a testable, biologically grounded foundation for precision acupuncture. The heterogeneous spatial distribution of NVI units may help explain acupoint functional specificity: The heterogeneous spatial distribution of NVI units forms the basis of a working hypothesis regarding acupoint functional specificity. We hypothesize that distal acral points, enriched in glomus bodies, may be preferentially suited for rapid neuromodulation in acute conditions, while proximal and trunk points may favor sustained neuro-immune regulation for chronic disorders. This distal–proximal gradient is proposed as a working hypothesis rather than a rigid dichotomy, acknowledging that every acupoint engages the full NVI triad simultaneously. NVI mechanosensitivity may also provide a rationale for optimizing stimulation parameters to enhance efficacy. By connecting peripheral tissue responses to systemic homeostatic regulation, the NVI model offers a unifying paradigm for standardizing protocols, improving clinical reproducibility, and expanding evidence-based acupuncture applications in complex neuro-immune disorders, facilitating its integration into global precision medicine.