{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T02:04:18Z","timestamp":1774922658678,"version":"3.50.1"},"reference-count":93,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T00:00:00Z","timestamp":1609113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio Ciencia innovacion y Universidades. Plan Nacional I+D+i,  Spain","award":["RT 2018-093677-B-100"],"award-info":[{"award-number":["RT 2018-093677-B-100"]}]},{"name":"Universidad Granada, Spain","award":["PPJIB2019.11"],"award-info":[{"award-number":["PPJIB2019.11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Transient receptor potential ankyrin member 1 (TRPA1) belongs to the family of thermo TRP cation channels that detect harmful temperatures, acids and numerous chemical pollutants. TRPA1 is expressed in nervous tissue, where it participates in the genesis of nociceptive signals in response to noxious stimuli and mediates mechanical hyperalgesia and allodynia associated with different neuropathies. The glutamate N-methyl-d-aspartate receptor (NMDAR), which plays a relevant role in allodynia to mechanical stimuli, is connected via histidine triad nucleotide-binding protein 1 (HINT1) and type 1 sigma receptor (\u03c31R) to mu-opioid receptors (MORs), which mediate the most potent pain relief. Notably, neuropathic pain causes a reduction in MOR antinociceptive efficacy, which can be reversed by blocking spinal NMDARs and TRPA1 channels. Thus, we studied whether TRPA1 channels form complexes with MORs and NMDARs that may be implicated in the aforementioned nociceptive signals. Our data suggest that TRPA1 channels functionally associate with MORs, delta opioid receptors and NMDARs in the dorsal root ganglia, the spinal cord and brain areas. These associations were altered in response to pharmacological interventions and the induction of inflammatory and also neuropathic pain. The MOR-TRPA1 and NMDAR-TRPA1 associations do not require HINT1 or \u03c31R but appear to be mediated by calcium-activated calmodulin. Thus, TRPA1 channels may associate with NMDARs to promote ascending acute and chronic pain signals and to control MOR antinociception.<\/jats:p>","DOI":"10.3390\/ijms22010229","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T20:03:03Z","timestamp":1609185783000},"page":"229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Calmodulin Supports TRPA1 Channel Association with Opioid Receptors and Glutamate NMDA Receptors in the Nervous Tissue"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0671-1156","authenticated-orcid":false,"given":"Elsa","family":"Cort\u00e9s-Montero","sequence":"first","affiliation":[{"name":"Department of Translational Neurosciences, Neuropharmacology, Cajal Institute, CSIC, Avenida Doctor Arce, 37. 28802 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Rodr\u00edguez-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Department of Translational Neurosciences, Neuropharmacology, Cajal Institute, CSIC, Avenida Doctor Arce, 37. 28802 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6968-0946","authenticated-orcid":false,"given":"M. Carmen","family":"Ruiz-Cantero","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neurosciences Institute (Biomedical Research Center), University of Granada and Biosanitary Research Institute, ibs. Granada, 18016 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrique J.","family":"Cobos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neurosciences Institute (Biomedical Research Center), University of Granada and Biosanitary Research Institute, ibs. Granada, 18016 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7211-4504","authenticated-orcid":false,"given":"Pilar","family":"S\u00e1nchez-Bl\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department of Translational Neurosciences, Neuropharmacology, Cajal Institute, CSIC, Avenida Doctor Arce, 37. 28802 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0053-258X","authenticated-orcid":false,"given":"Javier","family":"Garz\u00f3n-Ni\u00f1o","sequence":"additional","affiliation":[{"name":"Department of Translational Neurosciences, Neuropharmacology, Cajal Institute, CSIC, Avenida Doctor Arce, 37. 28802 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S0092-8674(02)00670-0","article-title":"The TRP channels, a remarkably functional family","volume":"108","author":"Montell","year":"2002","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nature02196","article-title":"TRP channels as cellular sensors","volume":"426","author":"Clapham","year":"2003","journal-title":"Nature"},{"key":"ref_3","first-page":"v","article-title":"Mammalian transient receptor potential (TRP) cation channels","volume":"Volume 223","author":"Nilius","year":"2014","journal-title":"Handbook of Experimental Pharmacology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S0092-8674(03)00158-2","article-title":"ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures","volume":"112","author":"Story","year":"2003","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nature14367","article-title":"Structure of the TRPA1 ion channel suggests regulatory mechanisms","volume":"520","author":"Paulsen","year":"2015","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.ceca.2007.04.004","article-title":"ThermoTRP channels as modular proteins with allosteric gating","volume":"42","author":"Latorre","year":"2007","journal-title":"Cell Calcium"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1085\/jgp.200810136","article-title":"TRPA1 and cold transduction: An unresolved issue?","volume":"133","author":"Caspani","year":"2009","journal-title":"J. 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