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  • Title: Attenuation of serotonin-induced itch by sumatriptan: possible involvement of endogenous opioids.
    Author: Haddadi NS, Foroutan A, Shakiba S, Afshari K, Ostadhadi S, Daneshpazhooh M, Dehpour AR.
    Journal: Arch Dermatol Res; 2018 Mar; 310(2):165-172. PubMed ID: 29352328.
    Abstract:
    Serotonin (5-hydroxytryptamine or 5-HT) is a neurotransmitter in itch and impaired serotonin signaling has been linked to a variety of itch conditions. Intradermal injection of 5-HT induces scratching behavior in mice through stimulation of 5-HT receptors. Previous studies have demonstrated that selective 5-HT1B/1D receptors agonists, including sumatriptan, inhibits neurotransmission. We have also reported that sumatriptan suppresses chloroquine-induced itch. Therefore, we investigated if sumatriptan has inhibitory effects on serotonin-induced itch in mice. Here, we show that intradermal and intraperitoneal administration of sumatriptan significantly reduce 5-HT-induced scratching behavior in mice. While intradermal injection of GR-127935, a selective 5-HT1B/1D receptors antagonist, reverses the anti-pruritic effects of sumatriptan. In addition, we show that intradermal and intraperitoneal naltrexone (NTX), a non-specific opioid receptor antagonist, and methylnaltrexone (MNTX), a peripherally acting opioid receptor antagonist, significantly decrease the 5-HT-induced scratching behavior. Additionally, combined treatment with sub-effective doses of sumatriptan and an opioid receptor antagonist, naltrexone, decreases 5-HT-evoked scratching responses. We conclude that sumatriptan inhibits 5-HT-induced itch by activating the peripheral 5-HT1B/1D receptors. Moreover, peripheral opioid receptors have a role in serotonin-induced itch, and anti-pruritic effects of sumatriptan seem to involve the opioid system. These data suggest that 5-HT1B/1D receptors agonists maybe useful to treat a variety of pathologic itch conditions with impaired serotonergic system.
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