Table 1.

Emerging pro-inflammatory and anti-inflammatory mediators in rodent models of pain

Mediator	Pain conditions	Sources	Targets	Roles in pain regulation	Refs
Pro-inflammatory chemokines, proteases, and Wnt pathway signaling molecule
CX3CL1	Nerve injury, cancer, arthritis	Neurons	CX3CR1 in microglia	Induces activation of microglia and promotes neuropathic pain, cancer pain and inflammatory pain	[72–75]
CXCL1	Nerve injury	Astrocytes	CXCR2 in neurons	Maintains central sensitization and neuropathic pain	[55]
CCL2	Nerve injury	Neurons Astrocytes	CCR2 in microglia CCR2 in neurons	Induces activation of microglia and neuropathic pain Maintains central sensitization and neuropathic pain	[33,78] [54,80]
CCL21	Nerve injury, spinal cord injury	Neurons	CXCR3 in microglia	Induces activation of microglia and neuropathic pain	[85,86]
CCL7	Nerve injury	Astrocytes	CCR2 in microglia	Maintains activation of microglia and neuropathic pain	[53]
MMP9	Nerve injury	DRG neurons	IL-1β signaling	Induces activation of microglia and neuropathic pain	[138]
MMP2	Nerve injury	Astrocytes satellite cells	IL-1β signaling	Maintains astrocyte and ERK activation and neuropathic pain	[138]
Cathepsin S	Nerve injury	Microglia	Neuronal CX3CL1	Promotes activation of microglia and neuropathic pain	[73, 147]
Caspase 6	Tissue injury	DRG neurons	TNF-α in microglia	Induces microglia activation and inflammatory pain	[48]
Wnt3a	Nerve injury cancer, EAE	Neurons Astrocytes	Frizzled/β-catenin	Enhances glial activation, cancer pain and neuropathic pain Induces neural and synaptic plasticity	[148, 150]
Anti-inflammatory pro-resolution lipid mediators (PRLMs)
PD1	Nerve injury Arthritis	Immune cells and glial cells?	GPCRS in neurons, immune cells, and glia	Inhibits TRPV1 and TNF-α signalling Prevents glial activation and neuropathic pain Reduces established inflammatory pain and neuropathic pain	[66,98]
RvE1	Nerve injury Arthritis	Immune cells and glial cells?	ChemR23 in neurons, immune cells, and glia	Inhibit TRPV1, ERK, and TNF-α signaling Reduces inflammation and microglia activation, reduces inflammatory pain and neuropathic pain	[99, 121]
RvD1	Arthritis	Immune cells and glial cells?	GRP32 and ALXR in neurons and glia	Inhibits TRPA1, TRPV3 and TRPV4	[99, 123, 124, 130]
RvD2	Arthritis	Immune cells and glial cells?	GPCRs in neurons and immune cells and glia	InhibitsTRPA1 and TRPV1 and reduces synaptic plasticity; Inhibits inflammatory pain	[123]
Lipoxins	Arthritis	Immune cells and glial cells?	ALXR in astrocytes	Inhibit JNK activation in astrocytes; Reduce inflammatory pain	[3]