| First Author | Li Z | Year | 2017 |
| Journal | Sci Signal | Volume | 10 |
| Issue | 487 | PubMed ID | 28698219 |
| Mgi Jnum | J:274502 | Mgi Id | MGI:6295265 |
| Doi | 10.1126/scisignal.aam5345 | Citation | Li Z, et al. (2017) The transcription factor C/EBPbeta in the dorsal root ganglion contributes to peripheral nerve trauma-induced nociceptive hypersensitivity. Sci Signal 10(487) |
| abstractText | Changes in gene transcription in the dorsal root ganglion (DRG) after nerve trauma contribute to the genesis of neuropathic pain. We report that peripheral nerve trauma caused by chronic constriction injury (CCI) increased the abundance of the transcription factor C/EBPbeta (CCAAT/enhancer binding protein beta) in the DRG. Blocking this increase mitigated the development and maintenance of CCI-induced mechanical, thermal, and cold pain hypersensitivities without affecting basal responses to acute pain and locomotor activity. Conversely, mimicking this increase produced hypersensitivity to mechanical, thermal, or cold pain. In the ipsilateral DRG, C/EBPbeta promoted a decrease in the abundance of the voltage-gated potassium channel subunit Kv1.2 and mu opioid receptor (MOR) at the mRNA and protein levels, which would be predicted to increase excitability in the ipsilateral DRG neurons and reduce the efficacy of morphine analgesia. These effects required C/EPBbeta-mediated transcriptional activation of Ehmt2 (euchromatic histone-lysine N-methyltransferase 2), which encodes G9a, an epigenetic silencer of the genes encoding Kv1.2 and MOR. Blocking the increase in C/EBPbeta in the DRG improved morphine analgesia after CCI. These results suggest that C/EBPbeta is an endogenous initiator of neuropathic pain and could be a potential target for the prevention and treatment of this disorder. |
