Figure 5.

The neuropeptide substance P (SP) contributes to neurogenic inflammation and pain through the activation of mast cells via MRGPRX2. Mast cells are found in close proximity to peripheral nerve endings. During tissue damage, SP released from peripheral nerve endings activates mast cells via MRGPRX2. Activated mast cells release several proinflammatory cytokines and chemokines such as CCL2 and CCL3, and they recruit immune cells in the injury site. These lead to the pathophysiology of neurogenic inflammation and peripheral neuron sensitization, resulting in pain sensation.