title: Epigenetic regulation of BDNF expression in the primary sensory neurons after peripheral nerve injury: implications in the development of neuropathic pain.
abstract: Brain-derived neurotrophic factor (BDNF) is known to be up-regulated in the dorsal root ganglion (DRG) after peripheral nerve injury, and to contribute to neuropathic pain. Here, we found that thermal hyperalgesia and mechanical allodynia at day 7 post-injury were inhibited only when anti-BDNF antibody was intrathecally administrated at day 2 post-injury. Consistent with behavioral results, Western blot analysis showed that the expression levels of BDNF protein in the spinal dorsal horn were markedly induced during early stage post-injury. Moreover, the maximal increase in BDNF mRNA expression in the DRG was observed at day 1 post-injury, and significantly elevated levels were sustained for at least 14 days. Four of five BDNF mRNA transcripts were up-regulated after nerve injury, and the most inducible transcript was exon I. Using a chromatin immunoprecipitation (ChIP) assay, we found that nerve injury promotes histone H3 and H4 acetylation, transcriptionally active modifications, at BDNF promoter I at day 1 post-injury, and the levels of histone acetylation remain elevated for at least 7 days. Taken together, our findings suggest that an initial increase in BDNF exon I expression controlled by epigenetic mechanisms might have a crucial role in the development of neuropathic pain.
authors: Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: H
authors: H
authors: Uchida
authors: Y
authors: Y
authors: Matsushita
authors: H
authors: H
authors: Ueda
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic / Q000502:physiology*; D005091:Exons / Q000235:genetics; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000209:etiology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D059348:Peripheral Nerve Injuries / Q000150:complications* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger