Figure 2.

Gabapentinoids inhibit calcium-mediated neurotransmitter release through effects on α2δ-1 subunits. They inhibit forward trafficking of α2δ-1 from the dorsal root ganglion, their recycling from endosomal compartments, thrombospondin-mediated processes and stimulate glutamate uptake by EAAT. Mechanisms not directly related to neurotransmitter release at dorsal horn include inhibition of descending serotonergic facilitation, stimulation of descending inhibition, anti-inflammatory actions and influence on the affective component of pain.²⁴