Lasmiditan Ameliorates Serotonergic Itch in Mice: Possible Involvement of 5-HT1F Receptors

Purpose Previously, some allergic conditions involving pruritus have been linked to migraine, raising the possibility that migraine and itching may be governed by similar underlying mechanisms. We aimed to investigate the efficacy of lasmiditan, a highly selective agonist of the 5-Hydroxytriptamin 1F receptor (5-HT1FR) and a recently approved medication for the treatment of migraine headaches, in ameliorating serotonergic itching. Methods Eight animals were randomly assigned to each of the study groups: (1) “Sham”: The sham group was given intradermal injections of normal saline (2) “Ctrl”: The control group was injected with intradermal doses of 5-HT, which was used to induce itching. (3) “Las 0.3”, “Las 1”, and “Las 3” groups: injected with 5-HT as well as intraperitoneal lasmiditan at different dose levels (0.3, 1, and 3 mg/kg, respectively). scratching behavior was recorded for 60 minutes, and the skin tissue of three mice was sampled at the end of the behavioral experiment to assess the levels of TLR-4, IL-31, 5-HT1FR, CGRP & TRPV4. Results In the present study, we found that Lasmiditan when administered at 1mg/kg effectively reduced serotonin-induced itching compared to the “Ctrl” group (P < 0.0001). Following the administration of Lasmiditan (1mg/kg), the expression levels of the 5-HT2A receptor significantly increased (P < 0.01). Further, the levels of TLR-4, IL-31, CGRP & TRPV4 were substantially reduced upon the administration of Lasmiditan (1mg/kg). Conclusions We found that Lasmiditan is effective in reducing serotonergic itch in mice through its interaction with the 5-HT1F receptor in the skin tissue of mice.