Cytokines and peripheral analgesia.

Tissue damage causes an inflammatory response in which cytokines contribute to a painful state. Local inflammation also leads to an enhanced expression of opioid peptides such as END within immune cells of inflamed tissue. These endogenous substances can be released by "releasing factors" such as CRF and IL-4 via activation of their receptors on the cell surface of inflammatory cells. Local application of CRE or IL-1 into inflamed tissue results in significant analgesia which is most likely mediated by a release of opioid peptides from immune cells within inflamed tissue. This mechanism of pain inhibition also seems to have a physiological role. Upon certain stressful stimuli analgesic effects seem to be mediated by a release of opioid peptides and a subsequent activation of peripheral opioid receptors. Locally expressed CRF but not IL-1 appear to trigger this release. Thus, inflammatory pain can be modulated both by exogenous CRF and IL-1 as well as endogenous CRF. These mechanisms are based on interaction between the immune and nervous systems. Both the initiation of pain and its control can be regarded as the body's response to prevent further injury, to support wound healing and to return to a normal function as quickly as possible.