Nitric oxide (NO), a short-lived molecule, has been identified as a potent biological mediator.⁴⁰ It plays an active role in many physiological processes such as vasodilatation, neural function, and inhibition of platelet aggregation, as well as in pathological processes such as inflammation.^{41 42 43} Immunological, activated monocyte and NK white blood cells synthesize NO, which contributes in part to their cytotoxic activity against tumor cells and bacteria.⁴⁴

NO is synthesized from the oxidation of the terminal guanido nitrogen atom of L-arginine by a family of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent enzyme, the NOS (nitric oxide synthetase).⁴³ It has been shown that micro-currents applied to acupuncture points 1.) mediate vasodilatation locally through nitric oxide^{45 46} 2.) signal afferent nerves via dorsal root ganglia to medulla thalamic tracts to the CNS and mediate opiod peptide synthesis and analgesia.^{13 15 16} NO is a primary vasodilator affecting the endothelial and smooth muscle cells of blood vessels.^{47 48} The induction of vasoldialtory neuropeptides and associated NO synthesis is a crucial aspect of the potential use of BEST therapy as an aid in wound healing, peripheral neuropathy, and ischemic conditions like thrombo-phlebitis and intermittent claudication of the limbs. Depletion of the nitric oxide pool in tissue inhibits healing and regeneration of normal metabolic functions due to stasis of extra cellular fluid and lymph flow. Ischemia leads to tissue acidification, degradation of the extra cellular milieu, and a further breakdown of cells. Local nitric oxide production is essential for adequate tissue perfusion and oxygenation of damaged tissue by its local vasodilatation mechanism.⁴¹ Neural peptide production plays a role in perfusion as well as the local and systemic up-regulation of both substances.