Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia

Numerous experimental studies provide evidence that proinflammatory cytokines induce or facilitate inflammatory as well as neuropathic pain and hyperalgesia. Direct receptor-mediated actions of cytokines on afferent nerve fibers have been reported as well as cytokine effects involving further mediators. The final outcome of cytokine action greatly depends on whether they act in the central of in the peripheral nervous system. Here we summarize recent findings on the peripheral mechanisms of action of three prototypic proinflammatory cytokines, interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha, with regards to pain and hyperalgesia.