Figure 1.

Diagram illustrating histamine receptor signalling—G_q pathway. Histamine binds to histamine receptors (H₁, H₂, or H₃ receptor subtypes) that are coupled with the G_q‐type protein. G_q α subunit activates PLC which hydrolyses phosphatidylinositol 4,5‐bisphosphate (PIP₂), subsequently producing DAG, that remains in the inner leaflet of the plasma membrane activating PKC, and water soluble inositol triphosphate (IP₃), which binds to http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=123 (IP₃R) and stimulates Ca²⁺ release from endoplasmic reticulum. This intracellular Ca²⁺ forms a complex with calmodulin (CaM) Ca²⁺CaM and induces PKC‐dependent phosphorylation. This suppresses the activity of potassium voltage‐gated channels type 7 (K_v7 channels), which depolarizes the neurons, and leads to the augmentation of neuronal excitability, which manifests as increased pain symptoms