Axonal accumulation of hyperpolarization-activated cyclic nucleotide-gated cation channels contributes to mechanical allodynia after peripheral nerve injury in rat.
Peripheral nerve injury causes neuropathic pain including mechanical allodynia and thermal hyperalgesia due to central and peripheral sensitization. Spontaneous ectopic discharges derived from dorsal root ganglion (DRG) neurons and from the sites of injury are a key factor in the initiation of this sensitization. Numerous studies have focused primarily on DRG neurons; however, the injured axons themselves likely play an equally important role. Previous studies of neuropathic pain rats with spinal nerve ligation (SNL) showed that the hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel in DRG neuronal bodies is important for the development of neuropathic pain. Here, we investigate the role of the axonal HCN channel in neuropathic pain rats. Using the chronic constriction injury (CCI) model, we found abundant axonal accumulation of HCN channel protein at the injured sites accompanied by a slight decrease in DRG neuronal bodies. The function of these accumulated channels was verified by local application of ZD7288, a specific HCN blocker, which significantly suppressed the ectopic discharges from injured nerve fibers with no effect on impulse conduction. Moreover, mechanical allodynia, but not thermal hyperalgesia, was relieved significantly by ZD7288. These results suggest that axonal HCN channel accumulation plays an important role in ectopic discharges from injured spinal nerves and contributes to the development of mechanical allodynia in neuropathic pain rats.
Jiang
Yu-Qiu
YQ
Neuroscience Research Institute, Peking University, Beijing 100083, China Department of Neurobiology, Peking University, Beijing 100083, China Key Laboratory for Neuroscience, Peking University, Beijing 100083, China Department of Pathology, Peking University, Beijing 100083, China.
Xing
Guo-Gang
GG
Wang
Sheng-Lan
SL
Tu
Hui-Yin
HY
Chi
Ye-Nan
YN
Li
Jie
J
Liu
Feng-Yu
FY
Han
Ji-Sheng
JS
Wan
You
Y
D000818:Animals; D001369:Axons / Q000378:metabolism*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000503:physiopathology*; D006930:Hyperalgesia / Q000503:physiopathology*; D015640:Ion Channel Gating; D008297:Male; D008564:Membrane Potentials; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000503:physiopathology*; D020671:Posterior Horn Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014110:Touch
D054815:Cyclic Nucleotide-Gated Cation Channels