Blocking the Spinal Fbxo3/CARM1/K⁺ Channel Epigenetic Silencing Pathway as a Strategy for Neuropathic Pain Relief.

ABSTRACT: 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 in

SUBMITTER: Hsieh MC 

PROVIDER: S-EPMC8423947 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature