What are the mechanisms that cause tissue damage from Raynaud’s attacks?

Although counterintuitive, much of the pain and potential tissue damage associated with the latter stages of a Raynaud’s attack occur after the constricted blood vessels have opened back up, which causes a rapid influx of oxygenated blood into the previously hypoxic (low oxygen) tissue. This triggers a type of ischemia-reperfusion injury, generating high levels of reactive oxygen species that are damaging to the tissue. In response to the damage, the immune system is mobilized, causing immune cells to move into the area and secrete high levels of pro-inflammatory cytokines. The characteristic deep-red and swollen appearance of the affected digits, as well as the pain and throbbing sensations, are caused by the inflammatory response. In extreme cases, the latter phase of Raynaud’s attacks can lead to the formation of blood clots, ulcers, or sores in the affected areas.^[1]