Download Time cited

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. Peking Univ, Key Lab Neurosci, Beijing 100083, Peoples R China
4. Peking Univ, Dept Pathol, Beijing 100083, Peoples R China
E-mail Addresses: [email protected]
1.
Jaggi, A.S. and Singh, N. (2010), Differential effect of spironolactone in chronic constriction
injury and vincristine-induced neuropathic pain in rats. European Journal of Pharmacology,
648 (1-3), 102-109.
2.
Gascon, E. and Moqrich, A. (2010), Heterogeneity in Primary Nociceptive Neurons: From
3.
Molecules to Pathology. Archives of Pharmacal Research, 33 (10), 1489-1507.
Takasu, K., Ono, H. and Tanabe, M. (2010), Spinal hyperpolarization-activated cyclic
nucleotide-gated cation channels at primary afferent terminals contribute to chronic pain. Pain,
4.
151 (1), 87-96.
Zhou, Y.H., Sun, L.H., Liu, Z.H., Bu, G.X., Pang, X.P., Sun, S.C., Qiao, G.F., Li, B.Y. and
Schild, J.H. (2010), Functional impact of the hyperpolarization-activated current on the
excitability of myelinated A-type vagal afferent neurons in the rat. Clinical and Experimental
5.
Pharmacology and Physiology, 37 (8), 852-861.
Ballo, A.W., Keene, J.C., Troy, P.J., Goeritz, M.L., Nadim, F. and Bucher, D. (2010),
6.
Dopamine Modulates I-h in a Motor Axon. Journal of Neuroscience, 30 (25), 8425-8434.
Wilson, G.W. and Garthwaite, J. (2010), Hyperpolarization-activated ion channels as targets
7.
for nitric oxide signalling in deep cerebellar nuclei. European Journal of Neuroscience, 31
(11), 1935-1945.
Colombo, E., Francisconi, S., Faravelli, L., Izzo, E. and Pevarello, P. (2010), Ion channel
8.
9.
blockers for the treatment of neuropathic pain. Future Medicinal Chemistry, 2 (5), 803-842.
Zhao, H., Gao, X.Y., Wang, D.X. and Zhang, Y.B. (2009), Effect of adenovirus-mediated gene
transfer of Olig1 on oligodendrocyte differentiation and remyelination in a rat model of focal
cerebral ischemia. Neural Regeneration Research, 4 (11), 862-867.
Krishnan, A.V., Lin, C.S.Y., Park, S.B. and Kiernan, M.C. (2009), Axonal ion channels from
bench to bedside: A translational neuroscience perspective. Progress in Neurobiology, 89 (3),
288-313.
10. Huang, L., Huang, Y.N. and Guo, H.L. (2009), Dominant expression of angiogenin in NeuN
positive cells in the focal ischemic rat brain. Journal of the Neurological Sciences, 285 (1-2),
220-223.
11. Cho, H.J., Staikopoulos, V., Furness, J.B. and Jennings, E.A. (2009), Inflammation-Induced
Increase in Hyperpolarization-Activated, Cyclic Nucleotide-Gated Channel Protein in
Trigeminal Ganglion Neurons and the Effect of Buprenorphine. Neuroscience, 162 (2),
453-461.
12. Han, J.S. (2009), Acupuncture Research Is Part of My Life. Pain Medicine, 10 (4), 611-618.
13. Wickenden, A.D., Maher, M.P. and Chaplan, S.R. (2009), HCN Pacemaker Channels and Pain:
A Drug Discovery Perspective. Current Pharmaceutical Design, 15 (18), 2149-2168.
14. Harriott, A.M. and Gold, M.S. (2009), Contribution of primary afferent channels to
neuropathic pain. Current Pain and Headache Reports, 13 (3), 197-207.
15. Dunlop, J., Vasilyev, D., Lu, P., Cummons, T. and Bowlby, M.R. (2009),
Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channels and Pain. Current
Pharmaceutical Design, 15 (15), 1767-1772.
16. Ballo, A.W. and Bucher, D. (2009), Complex Intrinsic Membrane Properties and Dopamine
Shape Spiking Activity in a Motor Axon. Journal of Neuroscience, 29 (16), 5062-5074.
17. Jiang, Y.Q., Sun, Q., Tu, H.Y. and Wan, Y. (2008), Characteristics of HCN channels and their
participation in neuropathic pain. Neurochemical Research, 33 (10), 1979-1989.