Calcineurin as a nociceptor modulator.
Calcineurin may be involved in affecting nociceptive processes in multiple circumstances. It is conceivable that interfering with calcineurin's normal role in contributing to glial resting membrane potential, via its effects on the ion channel (TRESK) [tandem-pore-domain weakly inward rectifying potassium channels (TWIK)-related spinal cord potassium channels] may facilitate nociception. Another aspect of calcineurin function may be its role in the pronociceptive signaling of nuclear factor of activated T-cells (NFAT). NFAT activation via mediators (e.g. Substance P, brain-derived neurotrophic factor, nerve growth factor, bradykinin) appears to be dependent on calcineurin function. This calcineurin-regulated NFAT signaling may subsequently lead to transcription of pronociceptive genes as well as upregulation of pronociceptive chemokine receptors in the dorsal root ganglion. In fact, multiple articles have described the clinical use of calcineurin-inhibitors leading to pain, a phenomenon referred to as calcineurin inhibitor-induced pain syndrome (CIPS). Thus, it appears that calcineurin functions may encompass actions which promote or dampen nociceptive processes. A greater understanding of the physiology of calcineurin, especially as it relates to modulating nociception may lead to the development of novel analgesic targets in attempts to optimally alleviate patient discomfort.
Smith
Howard S
HS
Albany Medical College, Department of Anesthesiology, Albany, NY 12208, USA. smithh@mail.amc.edu
D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D006801:Humans; D050778:NFATC Transcription Factors / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D065095:Calcineurin Inhibitors; C476574:KCNK18 protein, human; D050778:NFATC Transcription Factors; D015221:Potassium Channels; D019703:Calcineurin