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

Naoto Tomotsuka, Ryuji Kaku, Norihiko Obata, Yoshikazu Matsuoka, Hirotaka Kanzaki, Arata Taniguchi, Noriko Muto, Hiroki Omiya, Yoshitaro Itano, Tadasu Sato, Hiroyuki Ichikawa, Satoshi Mizobuchi, Hiroshi Morimatsu

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)415-423
Number of pages9
JournalJournal of Pain Research
Volume7
DOIs
Publication statusPublished - Jul 11 2014

Fingerprint

Bone Neoplasms
Brain-Derived Neurotrophic Factor
Spinal Ganglia
Up-Regulation
Pain
Nociceptors
Nerve Growth Factor
Exons
RNA
Cancer Pain
Neurons
Bone Marrow
Breast Neoplasms

Keywords

  • BDNF
  • Bone cancer pain
  • Chronic pain
  • Nerve growth factor

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Up-regulation of brain-derived neurotrophic factor in the dorsal root ganglion of the rat bone cancer pain model. / Tomotsuka, Naoto; Kaku, Ryuji; Obata, Norihiko; Matsuoka, Yoshikazu; Kanzaki, Hirotaka; Taniguchi, Arata; Muto, Noriko; Omiya, Hiroki; Itano, Yoshitaro; Sato, Tadasu; Ichikawa, Hiroyuki; Mizobuchi, Satoshi; Morimatsu, Hiroshi.

In: Journal of Pain Research, Vol. 7, 11.07.2014, p. 415-423.

Research output: Contribution to journalArticle

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 2014, 'Up-regulation of brain-derived neurotrophic factor in the dorsal root ganglion of the rat bone cancer pain model', Journal of Pain Research, vol. 7, pp. 415-423. https://doi.org/10.2147/JPR.S63527
Tomotsuka, Naoto ; Kaku, Ryuji ; Obata, Norihiko ; Matsuoka, Yoshikazu ; Kanzaki, Hirotaka ; Taniguchi, Arata ; Muto, Noriko ; Omiya, Hiroki ; Itano, Yoshitaro ; Sato, Tadasu ; Ichikawa, Hiroyuki ; Mizobuchi, Satoshi ; Morimatsu, Hiroshi. / Up-regulation of brain-derived neurotrophic factor in the dorsal root ganglion of the rat bone cancer pain model. In: Journal of Pain Research. 2014 ; Vol. 7. pp. 415-423.
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