Schematic diagram indicating proposed mechanisms for initiation/maintenance of cutaneous tactile allodynia after IR injury. IR injury is generated by oxygen free radicals, NFκB and pro-inflammatory cytokines (TNFα, IL-6, IL-1β) that produce injury to vascular endothelial cells, triggering microvascular dysfunction, including arterial vasospasms and capillary slow flow/no reflow in muscle. Resulting muscle ischemia leads to the generation of lactate and inflammatory mediators which activate ASIC and other receptors on muscle primary afferent fibers. Increased muscle lactate during exercise enhances muscle afferent activation and sensitizes these afferents. Activity in muscle afferents produces prolonged CNS sensitization that results in cutaneous tactile allodynia.