{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:19:59Z","timestamp":1792592399281,"version":"4.5.0"},"reference-count":74,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:sec><jats:title>Backgrouds:<\/jats:title><jats:p>ATP and P2X receptors play important roles in the modulation of trigeminal neuropathic pain, while the role of G protein-coupled P2Y<jats:sub>2<\/jats:sub>receptors and the underlying mechanisms are less clear. The threshold and frequency of action potentials, fast inactivating transient K+ channels (I<jats:sub>A<\/jats:sub>) are important regulators of membrane excitability in sensory neurons because of its vital role in the control of the spike onset. In this study, pain behavior tests, QT-RT-PCR, immunohistochemical staining, and patch-clamp recording, were used to investigate the role of P2Y<jats:sub>2<\/jats:sub>receptors in pain behaviour.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>In control rats: 1) UTP, an agonist of P2Y<jats:sub>2<\/jats:sub>\/P2Y<jats:sub>4<\/jats:sub>receptors, caused a significant decrease in the mean threshold intensities for evoking action potentials and a striking increase in the mean number of spikes evoked by TG neurons. 2) UTP significantly inhibited I<jats:sub>A<\/jats:sub>and the expression of Kv1.4, Kv3.4 and Kv4.2 subunits in TG neurons, which could be reversed by the P2 receptor antagonist suramin and the ERK antagonist U0126. In ION-CCI (chronic constriction injury of infraorbital nerve) rats: 1) mRNA levels of Kv1.4, Kv3.4 and Kv4.2 subunits were significantly decreased, while the protein level of phosphorylated ERK was significantly increased. 2) When blocking P2Y<jats:sub>2<\/jats:sub>receptors by suramin or injection of P2Y2R antisense oligodeoxynucleotides both led to a time- and dose-dependent reverse of allodynia in ION-CCI rats. 3) Injection of P2Y<jats:sub>2<\/jats:sub>receptor antisense oligodeoxynucleotides induced a pronounced decrease in phosphorylated ERK expression and a significant increase in Kv1.4, Kv3.4 and Kv4.2 subunit expression in trigeminal ganglia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>Our data suggest that inhibition of P2Y<jats:sub>2<\/jats:sub>receptors leads to down-regulation of ERK-mediated phosphorylation and increase of the expression of I<jats:sub>A<\/jats:sub>\u2013related Kv channels in trigeminal ganglion neurons, which might contribute to the clinical treatment of trigeminal neuropathic pain.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1744-8069-10-21","type":"journal-article","created":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T14:01:52Z","timestamp":1395151312000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":47,"title":["Inhibition of G Protein-Coupled P2Y<sub>2<\/sub>Receptor Induced Analgesia in a Rat Model of Trigeminal Neuropathic Pain"],"prefix":"10.1177","volume":"10","author":[{"given":"Na","family":"Li","sequence":"first","affiliation":[{"name":"Department of Physiology, The Key Laboratory of Molecular Neurobiology, Ministry of Education, Second Military Medical University, Shanghai 200433, P.R. 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