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The process is often initiated at the periphery through sensitization of nociceptors but is critically cemented within the CNS via enduring synaptic potentiation and a loss of inhibitory control, a state known as central sensitization

On the other hand, NF- can stimulate the urokinase-type plasminogen activator (uPA) through the lysosomal protease cathepsin B, inducing a metalloproteinase activity in the ECM, thus favoring cell migration and invasion

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