Actions of tumour necrosis factor (TNF) on hyperalgesia in health and in chronic inflammation. In the naive dorsal root ganglion (DRG), TNFα acts on peripheral cells to induce a proinflammatory cascade resulting in the release of mediators, such as prostaglandins, that activate nociceptive neurons, resulting in pain. After chronic inflammation, tumour necrosis factor receptor type 1(TNFR1) is up-regulated on DRG neurons, while TNFR2 is expressed by infiltrating macrophages. TNF can directly modulate neuronal function and act on peripheral cells and DRG macrophages to induce inflammatory mediators that can modulate neuronal function. This results in exaggerated pain.