biostudies-literatureHsieh MCMackay Memorial HospitalMinistry of Science and Technology, Taiwan1295-1315https://www.ebi.ac.uk/biostudies/studies/S-EPMC8423947biostudies-literatureUnknown18(2)Many epigenetic regulators are involved in pain-associated spinal plasticity. Coactivator-associated arginine methyltransferase 1 (CARM1), an epigenetic regulator of histone arginine methylation, is a highly interesting target in neuroplasticity. However, its potential contribution to spinal plasticity-associated neuropathic pain development remains poorly explored. Here, we report that nerve injury decreased the expression of spinal CARM1 and induced allodynia. Moreover, decreasing spinal CARM1 expression by Fbxo3-mediated CARM1 ubiquitination promoted H3R17me2 decrement at the K⁺ channel promoter, thereby causing K⁺ channel epigenetic silencing and the development of neuropathic pain. Remarkably, in naïve rats, decreasing spinal CARM1 using CARM1 siRNA or a CARM1 inNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeuticsBlocking the Spinal Fbxo3/CARM1/K⁺ Channel Epigenetic Silencing Pathway as a Strategy for Neuropathic Pain Relief.PMC8423947MOST 108-2320-B-715-002-MY3 and 108-2314-B-715-004-MY3MMH-MM-10705 and MMH-MM-10803MOST 108-2320-B-038-028MOST 108-2320-B-715-004-MY3MMH-MM-108-87Chen GDLai CYCheng JKLin TBHsieh MCHo YCPeng HYLee ASTseng KWWang HHYang PSNg SCfalseBlocking the Spinal Fbxo3/CARM1/K⁺ Channel Epigenetic Silencing Pathway as a Strategy for Neuropathic Pain Relief.Many epigenetic regulators are involved in pain-associated spinal plasticity. Coactivator-associated arginine methyltransferase 1 (CARM1), an epigenetic regulator of histone arginine methylation, is a highly interesting target in neuroplasticity. However, its potential contribution to spinal plasticity-associated neuropathic pain development remains poorly explored. Here, we report that nerve injury decreased the expression of spinal CARM1 and induced allodynia. Moreover, decreasing spinal CARM1 expression by Fbxo3-mediated CARM1 ubiquitination promoted H3R17me2 decrement at the K⁺ channel promoter, thereby causing K⁺ channel epigenetic silencing and the development of neuropathic pain. Remarkably, in naïve rats, decreasing spinal CARM1 using CARM1 siRNA or a CARM1 in2021-01-01T00:00:00Z2021 Apr2025-04-22T09:15:35.617Z2025-04-05T22:59:28.742ZS-EPMC84239473341568610.1007/s13311-020-00977-5