Table 1.

The role of immune cells in different locations in mediating pain during OA progression.

Types of Immune Cells	Sites
	Joint	DRG	Spinal Cord Dorsal Horn
Macrophages	Migration and M1 polarization in the synovium [19]. Releasing pain-promoting substances, such as IL-1β, IL-6, TNF-α, CCL2, PGE2, and NGF [20,21].	Infiltration and M1 polarization in the DRG [22]. The secretion of iNOS, IL-1β, TNF-α, IL-6, CCL2, and NGF induced pain [23].	The activation and proliferation of microglia occurred in the ipsilateral spinal dorsal horn [24]. Stimulating neurons through the release of IL-1β [25].
Neutrophils	Leading to pain sensation by secreting IL-1β and NE [23,26].	Neutrophil infiltration occurred during early-stage OA [27].
Mast Cells	The proportion of mast cells in synovium increased significantly [28]. The secretion of chymase, PGE2, PGD2, and NGF elicited pain [[29], [30], [31]].
Dendritic Cells		The proportion of dendritic cells increased [32].
T Cells	T-cell infiltration and Th1 polarization in the synovium resulting in pain [33,34].

OA, osteoarthritis; DRG, dorsal root ganglion; IL, Interleukin; TNF-α, tumor necrosis factor α; CCL2, C–C motif chemokine ligand 2; PGE2, prostaglandin E2; NGF, nerve growth factor; iNOS, inducible nitric oxide synthase; NE, norepinephrine; PAR, proteinase-activated receptor 2; MIA, monosodium iodoacetate; PGE2, prostaglandin E2; PGD2, prostaglandin D2; Th1, T-helper 1.