Table 2.

Regulation of immune cells by sensory neuron secretions.

Sensory Neuron Secretion	Pro-Inflammatory	Anti-Inflammatory
Nociceptive transmitter	SP induced activation of MAPK pathway in macrophages [63]. SP activated mast cells via Mrgprb2 [64]. CGRP promoted the release of CX3CL1 by endothelial cells, inducing macrophage chemotaxis and M1 polarization [65].	SP promoted M2 polarization of macrophages through inhibition of NF-kB/NLRP3 signaling pathway [66]. Intravenous injection of SP increased circulating IL-10 level, inducing macrophage M2 polarization [67]. CGRP promoted M2 polarization of macrophages via the PI3K/AKT signaling pathway [68].
Cytokines	CCL2, CSF1, CX3CL1 promoted macrophage chemotaxis in the DRG [69,70,71]. CXCL1 facilitated the chemotaxis of neutrophils in the DRG [72].
microRNA	miR-21 induced pro-inflammatory phenotype in macrophages [73].	miR-183 suppressed macrophage chemotaxis [74].
Vesicles	ATP-enriched vesicles released by spinal dorsal horn neurons induced activation of microglia [75].

SP, substance P; MAPK, mitogen-activated protein kinase; Mrgprb2, mas-related G protein-coupled receptor b2; CGRP, calcitonin gene-related peptide; NF-kB, Nuclear Factor kappa B; NLRP3, NOD-like receptor family pyrin domain containing 3; IL-10, Interleukin-10; PI3K, Phosphoinositide 3-kinase; AKT, Protein Kinase B; CX3CL1, C-X3-C motif chemokine ligand 1; CCL2, C–C motif chemokine ligand 2; DRG, dorsal root ganglion; CSF1, colony-stimulating factor 1; CCR2, C–C motif chemokine receptor 2.