title: Up-regulation of brain-derived neurotrophic factor in the dorsal root ganglion of the rat bone cancer pain model.
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.
authors: Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Naoto
authors: N
authors: Tomotsuka
authors: Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Ryuji
authors: R
authors: Kaku
authors: Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Norihiko
authors: N
authors: Obata
authors: Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Yoshikazu
authors: Y
authors: Matsuoka
authors: Department of Pharmacy, Okayama University Hospital, Okayama, Japan.
authors: Hirotaka
authors: H
authors: Kanzaki
authors: Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Arata
authors: A
authors: Taniguchi
authors: Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Noriko
authors: N
authors: Muto
authors: Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Hiroki
authors: H
authors: Omiya
authors: Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Yoshitaro
authors: Y
authors: Itano
authors: Department of Oral and Craniofacial Anatomy, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors: Tadasu
authors: T
authors: Sato
authors: Department of Oral and Craniofacial Anatomy, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors: Hiroyuki
authors: H
authors: Ichikawa
authors: Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Satoshi
authors: S
authors: Mizobuchi
authors: Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Hiroshi
authors: H
authors: Morimatsu
keywords: BDNF; bone cancer pain; chronic pain; nerve growth factor