Magnesium (Mg) is an essential divalent cation involved in more than 600 enzymatic reactions and plays a fundamental role in vascular, metabolic, and neural homeostasis. Although Mg is frequently discussed as an analgesic supplement, emerging evidence suggests that it acts as a neurovascular–metabolic modulator. Low magnesium status has been associated with endothelial dysfunction, atherosclerotic burden, impaired microcirculatory function, and overlapping ischemic and neuropathic pain phenotypes, although direct causal clinical evidence remains limited. This narrative review integrates mechanistic and clinical evidence across three intersecting domains: (1) the role of Mg in endothelial dysfunction, vascular calcification, and atherogenesis; (2) the contribution of Mg deficiency to ischemic pain through peripheral arterial disease and microcirculatory failure; and (3) the modulation of neuropathic pain through NMDA receptor antagonism, neuroinflammatory suppression, and maintenance of blood–brain barrier integrity. In populations with atherosclerosis, diabetes mellitus, or nutritional insufficiency, hypomagnesemia may serve as a unifying pathophysiological link connecting vascular injury to pain sensitization. The recognition of Mg not merely as an analgesic agent, but as a neurovascular interface regulator, may inform more comprehensive therapeutic strategies in chronic vascular and neuropathic pain syndromes. This review emphasizes nutritional magnesium status and biologically plausible mechanisms rather than presenting magnesium supplementation as an established treatment for vascular or neuropathic pain. The evidence is strongest for mechanistic vascular and neuropathic pathways, whereas direct clinical evidence for magnesium supplementation in PAD-related ischemic limb pain remains limited.
Yoon et al. (Sat,) studied this question.