Calcineurin as a Nociceptor Modulator

Abstract

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. Key words: Pain, neuropathic, calcineurin, NFAT, TRESK-[Tandem-pore-domain weakly inward rectifying potassium channels (TWIK)-related spinal cord potassium channels], CIPS (calcineurin-induced pain syndrome)