Figure 1. The interaction between macrophages and sensory
nerves.
- Sensory nerves release SP and CGRP promote either M1 phenotype or M2
phenotype.
- M1 macrophages produce pro-inflammatory cytokines including CCL2,
IL-1β, TNF-α, IL-6, PGE2, NGF, IGF-1 which combine to the specific
receptors on sensory nerves and enhance the activity of cation
channels like TRPV1/TRAV1 and NaV1.7/1.8/1.9 via cell signals (cAMP,
PKA, PKC, PI3K, MAPKs, NF-κB, JAK, STAT, and Src).
- Sensory nerves secret CCL2 and CX3CL1 which stimulate CCR2 and CX3CR1
on macrophages and microglia.
- M2 macrophages express IL-10, TGF-β, GPR37, opioid peptides. IL-10 can
downregulate TTX-S and Nav1.8 sodium channels. TGF-β inhibit
pro-inflammatory cytokine production through p38 MAPK. Opioid peptides
bind to opioid receptors µ (mu), δ (delta) and κ (kappa). Activation
of GPR37 induces phagocytosis.