Figure 7.

Hypothetical model illustrating the activation of DRG neurons and SGCs by BzATP. (A) 1. In phase I, BzATP strongly activates P2X7Rs, which are abundant in SGCs. To a smaller degree, BzATP may also activate other P2XR (e.g., P2X4R), which may be expressed on SGCs and large DRG neurons, as suggested by previous findings, and P2YR on SGCs. 2. In phase 2, the activation of SGCs and large neurons leads to Panx1 opening and release of ATP. 3. ATP further activates both small and large neurons and SGCs. 4. The activation of small neurons also leads to Panx1 opening and release of ATP to the extracellular space. 5. ATP, in turn, activates more SGCs and neurons. This process ends rapidly as ATP is degraded or cleared from the extracellular space. Neurons and SGCs return to the resting state, but neurons may become sensitized to subsequent stimulation. (B) The diagram illustrates the sequential activation of large neurons, SGCs, and small neurons after BzATP treatment.