Itch induced by peripheral mu opioid receptors is dependent on TRPV1-expressing neurons and alleviated by channel activation

Abstract Opioids remain the gold standard for the treatment of moderate to severe pain. However, their analgesic properties come with important side effects, including pruritus, which occurs frequently after systemic or neuraxial administration. Although part of the opioid-induced itch is mediated c...

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Autores principales:	Helvira Melo, Lilian Basso, Mircea Iftinca, Wallace K. MacNaughton, Morley D. Hollenberg, Derek M. McKay, Christophe Altier
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	TRPV1-expressing Neurons Transient Receptor Potential Vanilloid (TRPV1) TRPV1 Channel Opioid-induced Itch Itch Response Medicine R Science Q
Acceso en línea:	https://doaj.org/article/42ced415c4b94ea690383c643cde70f5
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spelling	oai:doaj.org-article:42ced415c4b94ea690383c643cde70f52021-12-02T15:07:50ZItch induced by peripheral mu opioid receptors is dependent on TRPV1-expressing neurons and alleviated by channel activation10.1038/s41598-018-33620-72045-2322https://doaj.org/article/42ced415c4b94ea690383c643cde70f52018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33620-7https://doaj.org/toc/2045-2322Abstract Opioids remain the gold standard for the treatment of moderate to severe pain. However, their analgesic properties come with important side effects, including pruritus, which occurs frequently after systemic or neuraxial administration. Although part of the opioid-induced itch is mediated centrally, recent evidence shows that the opioid receptor system in the skin also modulates itch. The goal of our study was to identify the peripherally located transducer mechanisms involved in opioid-induced pruritus. Scratching behaviors in response to an intradermal injection of the mu-opioid receptor (MOR) agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) was quantified in mast cell-, PAR2- and TRPV1-deficient mice or following ablation of TRPV1+ sensory neurons. We found that mast cells−/−, PAR-2−/−, or TRPV1−/− mice still exhibit DAMGO-induced itch responses. However, we show that ablation of TRPV1+ neurons or acute TRPV1 activation by capsaicin abolishes DAMGO-induced itch. Overall, our work shows that peripheral DAMGO-induced itch is dependent on the presence of TRPV1-expressing pruriceptors, but not the TRPV1 channel itself. Activation of these fibers by capsaicin prevents the opioid-induced itch.Helvira MeloLilian BassoMircea IftincaWallace K. MacNaughtonMorley D. HollenbergDerek M. McKayChristophe AltierNature PortfolioarticleTRPV1-expressing NeuronsTransient Receptor Potential Vanilloid (TRPV1)TRPV1 ChannelOpioid-induced ItchItch ResponseMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	TRPV1-expressing Neurons Transient Receptor Potential Vanilloid (TRPV1) TRPV1 Channel Opioid-induced Itch Itch Response Medicine R Science Q
spellingShingle	TRPV1-expressing Neurons Transient Receptor Potential Vanilloid (TRPV1) TRPV1 Channel Opioid-induced Itch Itch Response Medicine R Science Q Helvira Melo Lilian Basso Mircea Iftinca Wallace K. MacNaughton Morley D. Hollenberg Derek M. McKay Christophe Altier Itch induced by peripheral mu opioid receptors is dependent on TRPV1-expressing neurons and alleviated by channel activation
description	Abstract Opioids remain the gold standard for the treatment of moderate to severe pain. However, their analgesic properties come with important side effects, including pruritus, which occurs frequently after systemic or neuraxial administration. Although part of the opioid-induced itch is mediated centrally, recent evidence shows that the opioid receptor system in the skin also modulates itch. The goal of our study was to identify the peripherally located transducer mechanisms involved in opioid-induced pruritus. Scratching behaviors in response to an intradermal injection of the mu-opioid receptor (MOR) agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) was quantified in mast cell-, PAR2- and TRPV1-deficient mice or following ablation of TRPV1+ sensory neurons. We found that mast cells−/−, PAR-2−/−, or TRPV1−/− mice still exhibit DAMGO-induced itch responses. However, we show that ablation of TRPV1+ neurons or acute TRPV1 activation by capsaicin abolishes DAMGO-induced itch. Overall, our work shows that peripheral DAMGO-induced itch is dependent on the presence of TRPV1-expressing pruriceptors, but not the TRPV1 channel itself. Activation of these fibers by capsaicin prevents the opioid-induced itch.
format	article
author	Helvira Melo Lilian Basso Mircea Iftinca Wallace K. MacNaughton Morley D. Hollenberg Derek M. McKay Christophe Altier
author_facet	Helvira Melo Lilian Basso Mircea Iftinca Wallace K. MacNaughton Morley D. Hollenberg Derek M. McKay Christophe Altier
author_sort	Helvira Melo
title	Itch induced by peripheral mu opioid receptors is dependent on TRPV1-expressing neurons and alleviated by channel activation
title_short	Itch induced by peripheral mu opioid receptors is dependent on TRPV1-expressing neurons and alleviated by channel activation
title_full	Itch induced by peripheral mu opioid receptors is dependent on TRPV1-expressing neurons and alleviated by channel activation
title_fullStr	Itch induced by peripheral mu opioid receptors is dependent on TRPV1-expressing neurons and alleviated by channel activation
title_full_unstemmed	Itch induced by peripheral mu opioid receptors is dependent on TRPV1-expressing neurons and alleviated by channel activation
title_sort	itch induced by peripheral mu opioid receptors is dependent on trpv1-expressing neurons and alleviated by channel activation
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/42ced415c4b94ea690383c643cde70f5
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Itch induced by peripheral mu opioid receptors is dependent on TRPV1-expressing neurons and alleviated by channel activation

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