Fig. 5.

Schematic representation of the mechanisms of fractalkine release/action in the DRGs during peripheral inflammation. Inflammatory insult stimulates the production/release of a cascade of cytokines in the site of inflammation, culminating in the production of directly acting hypernociceptive mediators [prostanoids and sympathetic amines (SA)]. Nociceptive neuron sensitization caused by these mediators reaches the DRG, promoting the release of fractalkine that, in turn, binds to CX3CR1 expressed on SGCs and stimulates the production of TNF-α, IL-β, and PGE₂. These mediators might contribute to the maintenance of neuronal sensitization and, consequently, to inflammatory pain. PNN, primary nociceptive neuron.