The number of nerve fibers in the epidermis is increased during skin inflammation, which causes inflammatory pain. Sialyl glycosphingolipid, ganglioside, regulates axonal elongation and maintains axon morphology. Our previous study showed that Arthrobacter ureafaciens sialidase that degrades sialyl conjugates attenuated the number of epidermal nerve fibers and inflammatory pain. Moreover, F-11 cells derived from the dorsal root ganglion neuron treated with sialidase showed reduced neurite length and enhanced calcitonin gene-related peptide (CGRP)-immunoreactivity.
Thus, we investigated the effects of olcegepant, a CGRP receptor antagonist, on the inhibition of epidermal nerve fibers and inflammatory pain when treated with sialidase. One day after intraplantar injection of complete Freund‘s adjuvant into the mouse hind paw to initiate skin inflammation, olcegepant and sialidase were injected into inflamed skin. The number of nerve fibers in the epidermis was counted using immunofluorescent staining with anti-PGP 9.5 antibody. Olcegepant attenuated the analgesic effects and epidermal nerve fiber collapse by sialidase. These results suggested that sialidase degenerated epidermal nerve fibers in inflamed skin via CGRP receptor activation, resulting in analgesia.