Acupuncture-Associated Adenosine Signaling as a Candidate Modulator of Oligodendrocyte Precursor Cell Differentiation and Remyelination: A Testable Mechanistic Hypothesis

Remyelination depends on recruitment and differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes. Manual acupuncture can increase interstitial adenosine at the stimulated site, and adenosine receptors regulate oligodendroglial fate. However, peripheral adenosine release has not been shown to alter adenosine signaling within demyelinated central nervous system lesions. Receptor effects are also context-dependent: A1 receptor signaling can favor OPC differentiation, whereas A2A receptor activation inhibits differentiation in standard primary OPC cultures, with restorative effects reported in selected disease-specific models. Preclinical electroacupuncture studies have reported OPC differentiation, myelin-debris clearance, oligodendrocyte regeneration, or remyelination in rodent models, but adenosine-receptor causality has not been tested. We propose that manual acupuncture or electroacupuncture may modulate remyelination indirectly by initiating local purine release and peripheral neural, autonomic, humoral, or immune signals that alter lesion-level purine metabolism and the repair microenvironment. The direction and magnitude of the effect are predicted to depend on stimulation modality, lesion context, timing, receptor subtype, and OPC maturation stage. This article defines evidence boundaries, falsifiable predictions, and experiments measuring purines, receptor dependence, oligodendrocyte-lineage progression, ultrastructural remyelination, and conduction.