The immunosuppressant FK506 activates capsaicin- and bradykinin-sensitive DRG neurons and cutaneous C-fibers

Evaluation of the Antipruritic Effects of Topical Pimecrolimus in Non-Atopic Prurigo Nodularis: Results of a Randomized, Hydrocortisone-Controlled, Double-Blind Phase II Trial

“…By inhibition of the phosphatase calcineurin, dephosphorylation and activation of the transcription factor NF-AT (nuclear factor of activated T cells) is prevented, and synthesis of T cell-activated cytokines such as interleukin-2 is blocked [4,24]. It has been suggested that topical calcineurin inhibitors have a direct effect on heat receptors and the capsaicin receptor TRPV1 [8,9,25]. Activation of TRPV1 leads to neurogenic inflammation, which, in turn, can cause burning pain.…”

“…chronic irritative hand dermatitis, lichen sclerosus), including PN [6,7]. Pimecrolimus and tacrolimus are assumed to have, like capsaicin, an antipruritic effect by virtue of their influence on sensory cutaneous neurons and the phosphorylation of transient receptor potential subtype vanilloid 1 (TRPV1) receptor [8,9]. Therefore, pimecrolimus can be expected to have high antipruritic efficacy not only in the treatment of atopic dermatitis.…”

Effects of Topical Application of Tacrolimus on Acute Itch-Associated Responses in Mice

“…Topical application of tacrolimus causes skin burning and pruritus in some patients. 7) Tacrolimus increases intracellular Ca 2ϩ concentration in small population of capsaicin-sensitive sensory neurons and enhances discharges of heat-sensitive cutaneous C-fibers in vitro, 8) suggesting that tacrolimus acts directly on some capsaicin-sensitive primary afferents. These findings raise the possibility that tacrolimus acts directly on itch-signaling and capsaicin-sensitive primary afferents.…”

“…7) Tacrolimus produces the transient increase of discharge in cutaneous C-fibers in the skin-nerve preparation. 8) Tacrolimus also increases intracellular Ca 2ϩ concentration in a small population of sensory neurons in the primary culture and most of tacrolimus-sensitive neurons respond to capsaicin. 8) Capsaicin-sensitive sensory nerves may be involved in signaling of itch as well as pain.…”

“…8) Tacrolimus also increases intracellular Ca 2ϩ concentration in a small population of sensory neurons in the primary culture and most of tacrolimus-sensitive neurons respond to capsaicin. 8) Capsaicin-sensitive sensory nerves may be involved in signaling of itch as well as pain. 9) These findings suggest that tacrolimus directly acts on the primary sensory nerve, some of which are involved in itch and pain signaling.…”