TABLE 1.

Proinflammatory and anti‐inflammatory cytokines in discogenic pain

Cytokines	Category	Primary source	Function in neuroimmunologic pain	Expression during IVD degeneration
TNF‐α	Proinflammatory	Schwann cells, macrophages, mast cells, and neutrophils	Sensitize and enhance the excitability of neurons; promote sustained inflammatory response	Increased
IL‐1β	Proinflammatory	Macrophages, monocytes, dendritic cells	Increase excitability of neurons	Increased
IL‐6	Proinflammatory	Mast cells, macrophages, lymphocytes, neurons, and glial cells	Decrease thermal activation and pain threshold; increase excitability of neurons	Increased
IFN‐γ	Proinflammatory	Th1 cells; astrocytes and damaged neurons	Induce spontaneous pain and pain hypersensitivity	Increased
IL‐10	Anti‐inflammatory	T cells, B cells, macrophages, and mast cells	Inhibit the release IL‐1β, IL‐6, and TNF‐α	Reduced
TGF‐β	Anti‐inflammatory	Activated T cells and B cells	Inhibit proinflammatory cytokine (IL‐1β, IL‐6, and TNF‐α) release and promote expression of endogenous opioids	Increased
IL‐4	Anti‐inflammatory	T cells, mast cells, and granulocytes	Suppress the expression of IL‐1β, IL‐6, and TNF‐α	Increased

Abbreviations: IFN‐γ, interferon‐gamma; IL, interleukin; TGF‐β, transforming growth factor‐β; TNF‐α, tumor necrosis factor‐α.