{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:04:27Z","timestamp":1791266667553,"version":"4.1.0"},"reference-count":34,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012220","name":"Hercules Foundation","doi-asserted-by":"publisher","award":["AKUL\/09\/50"],"award-info":[{"award-number":["AKUL\/09\/50"]}],"id":[{"id":"10.13039\/100012220","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C1-TRPLe"],"award-info":[{"award-number":["C1-TRPLe"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G0B7620N"],"award-info":[{"award-number":["G0B7620N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005026","name":"Belgian Foundation Against Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005026","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Queen Elisabeth Medical Foundation for Neurosciences"},{"DOI":"10.13039\/501100004727","name":"Vlaams Instituut voor Biotechnologie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004727","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G0B5316N"],"award-info":[{"award-number":["G0B5316N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    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\n                    <jats:italic>Trpm3<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.7554\/elife.61103","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T08:00:35Z","timestamp":1599120035000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.61103","source":"Crossref","is-referenced-by-count":47,"title":["Upregulation of TRPM3 in nociceptors innervating inflamed tissue"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8429-7136","authenticated-orcid":true,"given":"Marie","family":"Mulier","sequence":"first","affiliation":[{"name":"Laboratory of Ion Channel Research (LICR), VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium"},{"name":"Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2242-4050","authenticated-orcid":true,"given":"Nele","family":"Van Ranst","sequence":"additional","affiliation":[{"name":"Laboratory of Ion Channel Research (LICR), VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium"},{"name":"Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikky","family":"Corthout","sequence":"additional","affiliation":[{"name":"VIB Bio Imaging Core and VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium"},{"name":"Department of Neuroscience, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5182-5358","authenticated-orcid":true,"given":"Sebastian","family":"Munck","sequence":"additional","affiliation":[{"name":"VIB Bio Imaging Core and VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium"},{"name":"Department of Neuroscience, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0009-2094","authenticated-orcid":true,"given":"Pieter","family":"Vanden Berghe","sequence":"additional","affiliation":[{"name":"Laboratory for Enteric NeuroScience (LENS), TARGID, Department of Chronic Diseases Metabolism and Ageing, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2502-0409","authenticated-orcid":true,"given":"Joris","family":"Vriens","sequence":"additional","affiliation":[{"name":"Laboratory of Endometrium, Endometriosis and Reproductive Medicine, G-PURE, Department of Development and Regeneration, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-5821","authenticated-orcid":true,"given":"Thomas","family":"Voets","sequence":"additional","affiliation":[{"name":"Laboratory of Ion Channel Research (LICR), VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium"},{"name":"Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauri","family":"Moilanen","sequence":"additional","affiliation":[{"name":"Laboratory of Ion Channel Research (LICR), VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium"},{"name":"Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2020,9,3]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"7840","DOI":"10.1523\/JNEUROSCI.0882-19.2019","article-title":"Promiscuous G-Protein-Coupled receptor inhibition of transient receptor potential melastatin 3 ion channels by g\u03b2\u03b3 subunits","volume":"39","author":"Alkhatib","year":"2019","journal-title":"The Journal of Neuroscience"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.cell.2009.09.028","article-title":"Cellular and molecular mechanisms of pain","volume":"139","author":"Basbaum","year":"2009","journal-title":"Cell"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.pain.2005.02.010","article-title":"Peripheral inflammation selectively increases TRPV1 function in IB4-positive sensory neurons from adult mouse","volume":"115","author":"Breese","year":"2005","journal-title":"Pain"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1126\/science.288.5464.306","article-title":"Impaired nociception and pain sensation in mice lacking the capsaicin receptor","volume":"288","author":"Caterina","year":"2000","journal-title":"Science"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.2","article-title":"Neuropathic pain","volume":"3","author":"Colloca","year":"2017","journal-title":"Nature Reviews Disease Primers"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/35012076","article-title":"Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia","volume":"405","author":"Davis","year":"2000","journal-title":"Nature"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1124\/mol.106.026740","article-title":"Mu-opioid receptor activation modulates transient receptor potential vanilloid 1 (TRPV1) currents in sensory neurons in a model of inflammatory pain","volume":"71","author":"Endres-Becker","year":"2007","journal-title":"Molecular Pharmacology"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1124\/jpet.104.079855","article-title":"AMG 9810 [(E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)acrylamide], a novel vanilloid receptor 1 (TRPV1) antagonist with antihyperalgesic properties","volume":"313","author":"Gavva","year":"2005","journal-title":"The Journal of Pharmacology and Experimental Therapeutics"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1124\/jpet.105.083915","article-title":"A-425619 [1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a novel transient receptor potential type V1 receptor antagonist, relieves pathophysiological pain associated with inflammation and tissue injury in rats","volume":"314","author":"Honore","year":"2005","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1016\/S1474-4422(14)70102-4","article-title":"Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms","volume":"13","author":"Jensen","year":"2014","journal-title":"The Lancet Neurology"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/s0896-6273(02)00908-x","article-title":"p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia","volume":"36","author":"Ji","year":"2002","journal-title":"Neuron"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1159\/000478986","article-title":"Antinociceptive effects of isosakuranetin in a rat model of peripheral neuropathy","volume":"100","author":"Jia","year":"2017","journal-title":"Pharmacology"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1097\/j.pain.0000000000000846","article-title":"Primidone inhibits TRPM3 and attenuates thermal nociception in vivo","volume":"158","author":"Kr\u00fcgel","year":"2017","journal-title":"Pain"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/emboj.2010.325","article-title":"TRPV1-lineage neurons are required for thermal sensation","volume":"30","author":"Mishra","year":"2011","journal-title":"The EMBO Journal"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.mcn.2009.10.006","article-title":"Ablation of TrpV1 neurons reveals their selective role in thermal pain sensation","volume":"43","author":"Mishra","year":"2010","journal-title":"Molecular and Cellular Neuroscience"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1016\/S0306-4522(98)00706-4","article-title":"Peripheral inflammation increases the capsaicin sensitivity of dorsal root ganglion neurons in a nerve growth factor-dependent manner","volume":"91","author":"Nicholas","year":"1999","journal-title":"Neuroscience"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1172\/JCI25437","article-title":"TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury","volume":"115","author":"Obata","year":"2005","journal-title":"Journal of Clinical Investigation"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/0304-3940(86)90180-1","article-title":"Sensory receptors in mammalian skin in an in vitro preparation","volume":"66","author":"Reeh","year":"1986","journal-title":"Neuroscience Letters"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.1177\/1744806920925425","article-title":"Satellite glial cells in sensory ganglia express functional transient receptor potential ankyrin 1 that is sensitized in neuropathic and inflammatory pain","volume":"16","author":"Shin","year":"2020","journal-title":"Molecular Pain"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1146\/annurev-pharmtox-010617-052534","article-title":"The opioid epidemic: crisis and solutions","volume":"58","author":"Skolnick","year":"2018","journal-title":"Annual Review of Pharmacology and Toxicology"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1124\/mol.113.086843","article-title":"Flavanones that selectively inhibit TRPM3 attenuate thermal nociception in vivo","volume":"84","author":"Straub","year":"2013","journal-title":"Molecular Pharmacology"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1038\/nn.3881","article-title":"Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing","volume":"18","author":"Usoskin","year":"2015","journal-title":"Nature Neuroscience"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1038\/nature26137","article-title":"A TRP channel trio mediates acute noxious heat sensing","volume":"555","author":"Vandewauw","year":"2018","journal-title":"Nature"},{"key":"bib24","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordhb\/9780190860509.001.0001","volume-title":"The Oxford Handbook of the Neurobiology of Pain","author":"Viana","year":"2019"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/j.tips.2019.07.004","article-title":"Targeting TRP channels - Valuable alternatives to combat pain, lower urinary tract disorders, and type 2 diabetes?","volume":"40","author":"Voets","year":"2019","journal-title":"Trends in Pharmacological Sciences"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.neuron.2012.02.008","article-title":"Deconstructing the neuropathic pain phenotype to reveal neural mechanisms","volume":"73","author":"von Hehn","year":"2012","journal-title":"Neuron"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/j.neuron.2011.02.051","article-title":"TRPM3 is a nociceptor channel involved in the detection of noxious heat","volume":"70","author":"Vriens","year":"2011","journal-title":"Neuron"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1038\/nrn3784","article-title":"Peripheral thermosensation in mammals","volume":"15","author":"Vriens","year":"2014","journal-title":"Nature Reviews Neuroscience"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/978-1-4939-1459-3_16","article-title":"Quantitative ultrasensitive bright-field RNA in situ hybridization with RNAscope","volume":"1211","author":"Wang","year":"2014","journal-title":"Methods in Molecular Biology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1097\/j.pain.0000000000001866","article-title":"Pharmacological target-focused transcriptomic analysis of native vs cultured human and mouse dorsal root ganglia","volume":"161","author":"Wangzhou","year":"2020","journal-title":"Pain"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"3131","DOI":"10.1523\/JNEUROSCI.4469-11.2012","article-title":"A Cre-dependent GCaMP3 reporter mouse for neuronal imaging in vivo","volume":"32","author":"Zariwala","year":"2012","journal-title":"Journal of Neuroscience"},{"key":"bib32","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3399","article-title":"Identification of a splice variant of mouse TRPA1 that regulates TRPA1 activity","volume":"4","author":"Zhou","year":"2013","journal-title":"Nature Communications"},{"key":"bib33","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.28728","article-title":"Efficient and accurate extraction of in vivo calcium signals from microendoscopic video data","volume":"7","author":"Zhou","year":"2018","journal-title":"eLife"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1038\/nprot.2008.223","article-title":"Phenotyping sensory nerve endings in vitro in the mouse","volume":"4","author":"Zimmermann","year":"2009","journal-title":"Nature Protocols"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/61103\/elife-61103-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/61103\/elife-61103-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/61103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:16:55Z","timestamp":1697059015000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/61103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,3]]},"references-count":34,"alternative-id":["10.7554\/eLife.61103"],"URL":"https:\/\/doi.org\/10.7554\/elife.61103","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.7554\/eLife.61103.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.61103.sa2","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,3]]},"article-number":"e61103"}}