As shown in Figure 2, TNF-α, as a crucial driver, can regulate cation channels to sensitize primary afferents in the peripheral nervous system, affect excitatory and inhibitory synaptic transmissions in CNS and evoke positive feedback between TNF-α and microglial activation to induce neuroinflammation, thus facilitating pain transmission, adverse pain-associated emotional reactions and cognitive deficits. Here, TNF is linked to Cognitive impairment.