Histone deacetylase inhibitors relieve morphine resistance in neuropathic pain after peripheral nerve injury

Neuropathic pain is often insensitive to morphine. Our previous study has demonstrated that neuronrestrictive silencer factor represses mu opioid receptor (MOP) gene expression in the dorsal root ganglion (DRG) via histone hypoacetylation-mediated mechanisms after peripheral nerve injury, thereby causing loss of peripheral morphine analgesia. Here, we showed that histone deacetylase (HDAC) inhibitors, such as trichostatin A and valproic acid, restored peripheral and systemic morphine analgesia in neuropathic pain. Also, these agents blocked nerve injury-induced MOP down-regulation in the DRG. These results suggest that HDAC inhibitors could serve as adjuvant analgesics to morphine for the management of neuropathic pain. (c) 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.