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Last data updates: 06 January 2011 Jiang, Y.Q., Xing, G.G., Wang, S.L., Tu, H.Y., Chi, Y.N., Li, J., Liu, F.Y., Han, J.S. and Wan, Y. (2008), Axonal accumulation of hyperpolarization-activated cyclic nucleotide-gated cation channels contributes to mechanical allodynia after peripheral nerve injury in rat. Pain, 137 (3), 495-506. Document type: Article Language: English Cited references: 55 Time cited: 17 Times self cited: 2 Abstract: 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. (C) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. Author Keywords: hyperpolarization-activated cyclic nucleotide-gated cation channel; I-h; chronic constriction injury (CCI); neuropathic pain; ectopic discharge Keywords Plus: Dorsal-Root Ganglion; Chronic Constriction Injury; Primary Afferent Neurons; Neuropathic Pain; Sciatic-Nerve; Sodium-Channels; Tactile Allodynia; Sensory Neurons; Pacemaker Channels; Ectopic Discharges Reprint Address: Wan, Y (reprint author), Peking Univ, Neurosci Res Inst, 38 Xue Yuan Rd, Beijing 100083, Peoples R China Addresses: 1. Peking Univ, Neurosci Res Inst, Beijing 100083, Peoples R China 2. Peking Univ, Dept Neurobiol, Beijing 100083, Peoples R China 3. 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