Figure 2.

Diagram illustrating histamine receptor signalling—G_s pathway. Histamine binds to the H₂ receptor subtype that is coupled with the G_s‐type protein. G_s α subunit activates AC, with subsequent production of cAMP, which then stimulates PKA. PKA‐dependent phosphorylation activates ligand gated α‐AMPA receptors, which open and facilitate influx of Na⁺ and, less commonly, Ca²⁺. PKA also suppresses K⁺ efflux through small conductance Ca²⁺‐activated potassium channels (SK channels). Both the activation of AMPA receptors and inhibition of SK channels depolarize the neurons, with consequent augmentation of their excitability and increased pain signalling