title: Histone deacetylase inhibitors relieve morphine resistance in neuropathic pain after peripheral nerve injury.
abstract: 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.
authors: Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors: Hitoshi
authors: H
authors: Uchida
authors: Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors: Yosuke
authors: Y
authors: Matsushita
authors: Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors: Kohei
authors: K
authors: Araki
authors: Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors: Takehiro
authors: T
authors: Mukae
authors: Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. Electronic address: ueda@nagasaki-u.ac.jp.
authors: Hiroshi
authors: H
authors: Ueda
mesh_terms: D000107:Acetylation; D000698:Analgesia; D000700:Analgesics; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects*; D004351:Drug Resistance / Q000187:drug effects*; D005727:Ganglia, Spinal / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000378:metabolism / Q000502:physiology; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids; D008297:Male; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology* / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology*; D059348:Peripheral Nerve Injuries / Q000150:complications*; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000700:Analgesics; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D017450:Receptors, Opioid, mu; C012589:trichostatin A; D014635:Valproic Acid; D009020:Morphine; D006655:Histone Deacetylases
keywords: Histone deacetylase inhibitor; Morphine; Neuropathic pain