Role of nerve growth factor-tyrosine kinase receptor A signaling in paclitaxel-induced peripheral neuropathy in rats.
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.
Department of Anesthesiology and Critical Care Medicine, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: yusuke.nakahashi@gmail.com.
Yusuke
Y
Nakahashi
Department of Anesthesiology and Critical Care Medicine, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan; Department of Anesthesiology, Niigata University Hospital, Niigata 951-8320, Japan; Department of Neuroanatomy, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: yoshinori.kamiya@gmail.com.
Yoshinori
Y
Kamiya
Department of Neuroanatomy, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: funako@med.yokohama-cu.ac.jp.
Kengo
K
Funakoshi
Department of Anesthesiology and Critical Care Medicine, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan; Department of Physiology, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: johney4@hotmail.com.
Tomoyuki
T
Miyazaki
Department of Anesthesiology and Critical Care Medicine, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: kaz-uch@umin.ac.jp.
Kazuhiro
K
Uchimoto
Department of Anesthesiology and Critical Care Medicine, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: ktojo-cib@umin.net.
Kentaro
K
Tojo
Department of Anesthesiology and Critical Care Medicine, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan; Department of Palliative Care Medicine, Yokohama City University Hospital, Yokohama 236-0004, Japan. Electronic address: k-ogawa@pd5.so-net.ne.jp.
Kenichi
K
Ogawa
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya 663-8501, Japan. Electronic address: tfukuoka@hyo-med.ac.jp.
Tetsuo
T
Fukuoka
Department of Anesthesiology and Critical Care Medicine, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: takigoto@yokohama-cu.ac.jp.
Takahisa
T
Goto
D000818:Animals; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D017931:DNA Primers; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D017239:Paclitaxel
Dorsal root ganglia; Nerve growth factor; Paclitaxel; Peripheral neuropathy; Spinal dorsal horn; Tyrosine kinase receptor A