Figure 1. Mechanisms of CACC activation in nociceptors.

Due to mechanical damage or inflammation, constituents of the inflammatory soup are released and activate GPCRs on nociceptors. Via heterotrimeric Gq/11 type G proteins and phospholipase C (PLC), intracellular Ca²⁺ levels are raised through the gating of either inositol trisphosphate (IP₃) receptors in the endoplasmic reticulum or TRPV1 channels in the plasma membrane. This Ca²⁺ elevation leads to the opening of ANO1 or possibly other CaCCs, and the resulting Cl⁻ efflux causes depolarization and increased action potential propagation towards the spinal cord.