trichostatin-a and Peripheral-Nerve-Injuries

Neuropathic pain is often insensitive to morphine. Our previous study has demonstrated that neuron-restrictive 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.

Topics: Acetylation; Analgesia; Analgesics; Animals; Down-Regulation; Drug Resistance; Ganglia, Spinal; Gene Expression; Histone Deacetylase Inhibitors; Histone Deacetylases; Histones; Hydroxamic Acids; Male; Mice, Inbred C57BL; Morphine; Neuralgia; Peripheral Nerve Injuries; Receptors, Opioid, mu; Valproic Acid