Up-regulation of brain-derived neurotrophic factor in the dorsal root ganglion of the rat bone cancer pain model
Autor: | Satoshi Mizobuchi, Ryuji Kaku, Norihiko Obata, Yoshikazu Matsuoka, Tadasu Sato, Arata Taniguchi, Hiroshi Morimatsu, Naoto Tomotsuka, Hiroki Omiya, Yoshitaro Itano, Noriko Muto, Hiroyuki Ichikawa, Hirotaka Kanzaki |
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Rok vydání: | 2014 |
Předmět: |
medicine.medical_specialty
Pathology nerve growth factor Dorsal root ganglion Downregulation and upregulation Neurotrophic factors Internal medicine medicine Journal of Pain Research Original Research Brain-derived neurotrophic factor biology Bone cancer business.industry Chronic pain medicine.disease BDNF Anesthesiology and Pain Medicine Endocrinology Nerve growth factor medicine.anatomical_structure nervous system biology.protein bone cancer pain chronic pain business Neurotrophin |
Zdroj: | Journal of Pain Research |
ISSN: | 1178-7090 |
DOI: | 10.2147/jpr.s63527 |
Popis: | Naoto Tomotsuka,1 Ryuji Kaku,1 Norihiko Obata,1 Yoshikazu Matsuoka,1 Hirotaka Kanzaki,2 Arata Taniguchi,1 Noriko Muto,1 Hiroki Omiya,1 Yoshitaro Itano,1 Tadasu Sato,3 Hiroyuki Ichikawa,3 Satoshi Mizobuchi,1 Hiroshi Morimatsu1 1Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; 2Department of Pharmacy, Okayama University Hospital, Okayama, Japan; 3Department of Oral and Craniofacial Anatomy, Tohoku University Graduate School of Dentistry, Sendai, Japan Abstract: Metastatic bone cancer causes severe pain, but current treatments often provide insufficient pain relief. One of the reasons is that mechanisms underlying bone cancer pain are not solved completely. Our previous studies have shown that brain-derived neurotrophic factor (BDNF), known as a member of the neurotrophic family, is an important molecule in the pathological pain state in some pain models. We hypothesized that expression changes of BDNF may be one of the factors related to bone cancer pain; in this study, we investigated changes of BDNF expression in dorsal root ganglia in a rat bone cancer pain model. As we expected, BDNF mRNA (messenger ribonucleic acid) and protein were significantly increased in L3 dorsal root ganglia after intra-tibial inoculation of MRMT-1 rat breast cancer cells. Among the eleven splice-variants of BDNF mRNA, exon 1–9 variant increased predominantly. Interestingly, the up-regulation of BDNF is localized in small neurons (mostly nociceptive neurons) but not in medium or large neurons (non-nociceptive neurons). Further, expression of nerve growth factor (NGF), which is known as a specific promoter of BDNF exon 1–9 variant, was significantly increased in tibial bone marrow. Our findings suggest that BDNF is a key molecule in bone cancer pain, and NGF-BDNF cascade possibly develops bone cancer pain. Keywords: BDNF, bone cancer pain, chronic pain, nerve growth factor |
Databáze: | OpenAIRE |
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