Abstract

Cytokines are a heterogeneous group of polypeptides that were originally described to mediate activation of the immune system and inflammatory responses. Most of them have meanwhile been shown to be also produced by and act on the peripheral and central nervous system. There is ample evidence from experimental studies that proinflammatory cytokines induce or increase neuropathic pain as well as inflammatory pain. Direct actions of cytokines on afferent nerve fibers have been shown as well as actions involving further mediators such as prostaglandins or nerve growth factor. Inhibition of proinflammatory cytokines, either by synthesis inhibitors, inhibitors of cleavage from the cell membrane, by direct antagonists, or by anti-inflammatory antibodies, reduces pain and hyperalgesia in most models studied. Studies with cytokine knock-out animals often lead to different results from the pharmacological studies. This is in part due to compensatory mechanisms in the animals combined with the high redundancy of the cytokine system. Preliminary data from human studies are encouraging insofar as in the future, cytokine inhibition may add to the panel of treatment modalities for neuropathic pain.