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Attenuation of serotonin-induced itch by sumatriptan: possible involvement of endogenous opioids

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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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Acknowledgements

This study was supported by the Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran (95-02-30-32135).

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Authors and Affiliations

  1. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Nazgol-Sadat Haddadi, Arash Foroutan, Saeed Shakiba, Khashayar Afshari & Ahmad-Reza Dehpour

  2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran

    Nazgol-Sadat Haddadi, Arash Foroutan, Saeed Shakiba, Khashayar Afshari, Sattar Ostadhadi & Ahmad-Reza Dehpour

  3. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Sattar Ostadhadi & Ahmad-Reza Dehpour

  4. Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Daneshpazhooh

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  1. Nazgol-Sadat Haddadi
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  2. Arash Foroutan
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Correspondence to Ahmad-Reza Dehpour.

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The authors declare that they have no conflict of interest.

Ethical approval

Experiments were performed according the European Communities Council Directive of 24 November 1986 (86/609/EEC) and Guide to the Care and Use of Experimental Animals [37] with approval of committee for animal ethics and experiments at Tehran University of Medical Sciences, Tehran, Iran. In addition, this article does not contain any studies with human participants performed by any of the authors.

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Deceased: Sattar Ostadhadi in 10/2017.

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Haddadi, NS., Foroutan, A., Shakiba, S. et al. Attenuation of serotonin-induced itch by sumatriptan: possible involvement of endogenous opioids. Arch Dermatol Res 310, 165–172 (2018). https://doi.org/10.1007/s00403-018-1809-9

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