Tissue plasminogen activator contributes to morphine tolerance and induces mechanical allodynia via astrocytic IL-1β and ERK signaling in the spinal cord of mice

Chronic morphine treatment induces up-regulation of tissue plasminogen activator (tPA) in spinal cord astrocytes. tPA causes activation of ERK and increased synthesis of IL-1β, leading to antinociceptive tolerance. Spinal injection of tPA also induces astrogliosis and pain hypersensitivity.