Fig. 1

Schematic illustration of P2X7 receptor involvement in sequential signaling effects on microglia and neuronal activity in CPSP. The figure illustrates our concepts of the involvement of P2X7 receptor in normal and CPSP states, combined with previous reports of P2X4 and P2X7 receptor function and their roles in other types of neuropathic pain. In the normal state, P2X4 and P2X7 receptor expression is low in neurons, astrocytes, glia, and resting microglial cells. In the CPSP state, the pathological enhancement of ATP release to surrounding tissue after stroke insult may lead to an increase in both P2X4 and P2X7 receptor expression and activation. Such activation has been reported to promote synaptic glutamate release and the abnormally high production of IL-1β, TNF-α, and BDNF. Consequently, IL-1β has also been reported to alter glutamate transmission in the CNS, and BDNF has been shown to alter chloride ion flux via TrkB and GABA receptors. Such sequential elevations of signaling molecules at sites of damage, combined with blood cell infiltration, can affect the activity of astrocytes, microglia, and neurons, thus resulting in neuronal hyperexcitability that is promoted by peripheral pain sensitivity and leading to the pathogenesis of CPSP. Figure adapted from Kuan et al. [68]