Uchida Hitoshi, Matsushita Yosuke, Araki Kohei, Mukae Takehiro, Ueda Hiroshi
Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
J Pharmacol Sci. 2015 Aug;128(4):208-11. doi: 10.1016/j.jphs.2015.07.040. Epub 2015 Aug 6.
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.
神经性疼痛通常对吗啡不敏感。我们之前的研究表明，神经元限制性沉默因子通过外周神经损伤后组蛋白低乙酰化介导的机制抑制背根神经节（DRG）中的μ阿片受体（MOP）基因表达，从而导致外周吗啡镇痛作用丧失。在此，我们表明组蛋白脱乙酰酶（HDAC）抑制剂，如曲古抑菌素A和丙戊酸，可恢复神经性疼痛中外周和全身的吗啡镇痛作用。此外，这些药物可阻断神经损伤诱导的DRG中MOP的下调。这些结果表明，HDAC抑制剂可作为吗啡的辅助镇痛药用于治疗神经性疼痛。
