Mode of action of cytokines on nociceptive neurons.
Cytokines are pluripotent soluble proteins secreted by immune and glial cells and are key elements in the induction and maintenance of pain. They are categorized as pro-inflammatory cytokines, which are mostly algesic, and anti-inflammatory cytokines, which have analgesic properties. Progress has been made in understanding the mechanisms underlying the action of cytokines in pain. To date, several direct and indirect pathways are known that link cytokines with nociception or hyperalgesia. Cytokines may act via specific cytokine receptors inducing downstream signal transduction cascades, which then modulate the function of other receptors like the ionotropic glutamate receptor, the transient vanilloid receptors, or sodium channels. This receptor activation, either through amplification of the inflammatory reaction, or through direct modulation of ion channel currents, then results in pain sensation. Following up on results from animal experiments, cytokine profiles have recently been investigated in human pain states. An imbalance of pro- and anti-inflammatory cytokine expression may be of importance for individual pain susceptibility. Individual cytokine profiles may be of diagnostic importance in chronic pain states, and, in the future, might guide the choice of treatment.
Uçeyler
Nurcan
N
Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany.
Schäfers
Maria
M
Sommer
Claudia
C
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D020932:Nerve Growth Factor / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism
D016207:Cytokines; D009479:Neuropeptides; D011453:Prostaglandins; D018121:Receptors, Cytokine; D017470:Receptors, Glutamate; D050916:TRPV Cation Channels; D020932:Nerve Growth Factor; D012964:Sodium; D011188:Potassium; D002118:Calcium