Back to Journals » Journal of Pain Research » Volume 7

Up-regulation of brain-derived neurotrophic factor in the dorsal root ganglion of the rat bone cancer pain model

Authors Tomotsuka N, Kaku R, Obata N, Matsuoka Y, Kanzaki H, Taniguchi A, Muto N, Omiya H, Itano Y, Sato T, Ichikawa H, Mizobuchi S, Morimatsu H

Received 4 March 2014

Accepted for publication 9 April 2014

Published 11 July 2014 Volume 2014:7 Pages 415—423


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]