BIX01294, a G9a inhibitor, alleviates nerve injury-induced pain hypersensitivities during both development and maintenance periods.

Genetic knockdown or knockout of the histone methytransferase G9a in the injured dorsal root ganglion (DRG) has been shown to alleviate neuropathic pain development. However, the application of genetic strategy in clinic is highly limited. The present study sought to examine the effect of intrathecal BIX01294, a specific G9a inhibitor, on the development and maintenance of pain hypersensitivities caused by unilateral L5 spinal nerve injury (SNL) or chronic constriction injury (CCI) to the sciatic nerve in rats. We found that intrathecal administration of BIX01294 reduced SNL- or CCI-induced mechanical allodynia, thermal hyperalgesia and cold allodynia not only in the development period but also in the maintenance period. These effects were dose-dependent. Intrathecal administration of BIX01294 also blocked the SNL-induced increase in the level of H3K9me2, a marker of G9a activity, and reversed SNL-induced downregulation of mRNA, mRNA, mRNA, mRNA, and mRNA, the downstream targets of G9a, in the ipsilateral L5 DRG. These findings further implicate that G9a as a potential target in the management of neuropathic pain.