Role of nerve growth factor-tyrosine kinase receptor A signaling in paclitaxel-induced peripheral neuropathy in rats
详细信息 查看全文
- 作者：Yusuke Nakahashi ; Yoshinori Kamiya ; Kengo Funakoshi ; Tomoyuki Miyazaki ; Kazuhiro Uchimoto ; Kentaro Tojo ; Kenichi Ogawa ; Tetsuo Fukuoka ; Takahisa Goto
- 关键词：BDNF ; brain-derived neurotrophic factor ; DH ; spinal dorsal horn ; DRG ; dorsal root ganglia ; I.P. ; intraperitoneal ; I.T. ; intrathecal ; NEDD4-2 ; neural precursor cell-expressed developmentally downregulated 4-2 ; NGF ; nerve growth factor ; p75NTR ; p75 neurotrophin receptor ; qPCR ; quantitative real-time polymerase chain reaction ; SKIN ; hindpaw skin ; SN ; sciatic nerve ; SNL ; spinal nerve ligation ; TrkA ; tyrosine kinase receptor A ; TrkB ; tyrosine kinase receptor B
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：14 February, 2014
- 年：2014
- 卷：444
- 期：3
- 页码：415-419
- 全文大小：714 K
文摘
The mechanisms underlying paclitaxel-induced peripheral neuropathy remain unknown. Nerve growth factor (NGF) is a representative neurotrophic factor that maintains neuronal function, promotes survival, and mediates neuropathic pain. We investigated expression levels of NGF and its receptors in the dorsal root ganglia (DRG) and spinal dorsal horn (DH) following paclitaxel treatment. Intraperitoneal (I.P.) administration of paclitaxel induced significant mechanical hypersensitivity and cold allodynia in rats, significantly increased the expression of NGF and its receptor tyrosine kinase receptor A (trkA) in the DRG, and increased NGF expression in the DH. In contrast, paclitaxel treatment did not alter the mRNA levels of NGF or its receptors in the DRG, DH, sciatic nerve, or hindpaw skin. Moreover, expression of NEDD4-2, a negative regulator of trkA, was significantly increased in the DRG of paclitaxel-treated rats. Intrathecal (I.T.) administration of the tyrosine kinase receptor inhibitor k252a significantly alleviated mechanical hypersensitivity in paclitaxel-treated rats. Our results suggest that NGF-trkA signaling is involved in mechanical allodynia in paclitaxel-induced neuropathy.