Upregulation of TRPM3 in nociceptors innervating inflamed tissue
Genetic ablation or pharmacological inhibition of the heat-activated cation channel TRPM3 alleviates inflammatory heat hyperalgesia, but the underlying mechanisms are unknown. We induced unilateral inflammation of the hind paw in mice, and directly compared expression and function of TRPM3 and two o...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/61103 |
| _version_ | 1811235943830519808 |
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| author | Marie Mulier Nele Van Ranst Nikky Corthout Sebastian Munck Pieter Vanden Berghe Joris Vriens Thomas Voets Lauri Moilanen |
| author_facet | Marie Mulier Nele Van Ranst Nikky Corthout Sebastian Munck Pieter Vanden Berghe Joris Vriens Thomas Voets Lauri Moilanen |
| author_sort | Marie Mulier |
| collection | DOAJ |
| description | Genetic ablation or pharmacological inhibition of the heat-activated cation channel TRPM3 alleviates inflammatory heat hyperalgesia, but the underlying mechanisms are unknown. We induced unilateral inflammation of the hind paw in mice, and directly compared expression and function of TRPM3 and two other heat-activated TRP channels (TRPV1 and TRPA1) in sensory neurons innervating the ipsilateral and contralateral paw. We detected increased Trpm3 mRNA levels in dorsal root ganglion neurons innervating the inflamed paw, and augmented TRP channel-mediated calcium responses, both in the cell bodies and the intact peripheral endings of nociceptors. In particular, inflammation provoked a pronounced increase in nociceptors with functional co-expression of TRPM3, TRPV1 and TRPA1. Finally, pharmacological inhibition of TRPM3 dampened TRPV1- and TRPA1-mediated responses in nociceptors innervating the inflamed paw, but not in those innervating healthy tissue. These insights into the mechanisms underlying inflammatory heat hypersensitivity provide a rationale for developing TRPM3 antagonists to treat pathological pain. |
| first_indexed | 2024-04-12T12:00:51Z |
| format | Article |
| id | doaj.art-f8c6e3617b43421093f9ed8288d5171b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:00:51Z |
| publishDate | 2020-09-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj.art-f8c6e3617b43421093f9ed8288d5171b2022-12-22T03:33:51ZengeLife Sciences Publications LtdeLife2050-084X2020-09-01910.7554/eLife.61103Upregulation of TRPM3 in nociceptors innervating inflamed tissueMarie Mulier0https://orcid.org/0000-0001-8429-7136Nele Van Ranst1https://orcid.org/0000-0003-2242-4050Nikky Corthout2Sebastian Munck3https://orcid.org/0000-0002-5182-5358Pieter Vanden Berghe4https://orcid.org/0000-0002-0009-2094Joris Vriens5https://orcid.org/0000-0002-2502-0409Thomas Voets6https://orcid.org/0000-0001-5526-5821Lauri Moilanen7Laboratory of Ion Channel Research (LICR), VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium; Department of Cellular and Molecular Medicine, KU Leuven, Leuven, BelgiumLaboratory of Ion Channel Research (LICR), VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium; Department of Cellular and Molecular Medicine, KU Leuven, Leuven, BelgiumVIB Bio Imaging Core and VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium; Department of Neuroscience, KU Leuven, Leuven, BelgiumVIB Bio Imaging Core and VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium; Department of Neuroscience, KU Leuven, Leuven, BelgiumLaboratory for Enteric NeuroScience (LENS), TARGID, Department of Chronic Diseases Metabolism and Ageing, KU Leuven, Leuven, BelgiumLaboratory of Endometrium, Endometriosis and Reproductive Medicine, G-PURE, Department of Development and Regeneration, KU Leuven, Leuven, BelgiumLaboratory of Ion Channel Research (LICR), VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium; Department of Cellular and Molecular Medicine, KU Leuven, Leuven, BelgiumLaboratory of Ion Channel Research (LICR), VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium; Department of Cellular and Molecular Medicine, KU Leuven, Leuven, BelgiumGenetic ablation or pharmacological inhibition of the heat-activated cation channel TRPM3 alleviates inflammatory heat hyperalgesia, but the underlying mechanisms are unknown. We induced unilateral inflammation of the hind paw in mice, and directly compared expression and function of TRPM3 and two other heat-activated TRP channels (TRPV1 and TRPA1) in sensory neurons innervating the ipsilateral and contralateral paw. We detected increased Trpm3 mRNA levels in dorsal root ganglion neurons innervating the inflamed paw, and augmented TRP channel-mediated calcium responses, both in the cell bodies and the intact peripheral endings of nociceptors. In particular, inflammation provoked a pronounced increase in nociceptors with functional co-expression of TRPM3, TRPV1 and TRPA1. Finally, pharmacological inhibition of TRPM3 dampened TRPV1- and TRPA1-mediated responses in nociceptors innervating the inflamed paw, but not in those innervating healthy tissue. These insights into the mechanisms underlying inflammatory heat hypersensitivity provide a rationale for developing TRPM3 antagonists to treat pathological pain.https://elifesciences.org/articles/61103TRP channelsinflammatory painsensory neurons |
| spellingShingle | Marie Mulier Nele Van Ranst Nikky Corthout Sebastian Munck Pieter Vanden Berghe Joris Vriens Thomas Voets Lauri Moilanen Upregulation of TRPM3 in nociceptors innervating inflamed tissue eLife TRP channels inflammatory pain sensory neurons |
| title | Upregulation of TRPM3 in nociceptors innervating inflamed tissue |
| title_full | Upregulation of TRPM3 in nociceptors innervating inflamed tissue |
| title_fullStr | Upregulation of TRPM3 in nociceptors innervating inflamed tissue |
| title_full_unstemmed | Upregulation of TRPM3 in nociceptors innervating inflamed tissue |
| title_short | Upregulation of TRPM3 in nociceptors innervating inflamed tissue |
| title_sort | upregulation of trpm3 in nociceptors innervating inflamed tissue |
| topic | TRP channels inflammatory pain sensory neurons |
| url | https://elifesciences.org/articles/61103 |
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