Contribution of hyperpolarization-activated channels to heat hypersensitivity and ongoing activity in the neuritis model.

Abstract

Neuritis can cause pain hypersensitivities in the absence of axonal degeneration. Such hypersensitivities are reputed to be maintained by ongoing activity into the spinal cord, which, in the neuritis model, is mainly generated from intact C-fiber neurons. The hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels has been implicated in nerve injury-induced pain hypersensitivities. The present study has examined the role of these channels in the development of heat and mechanical hypersensitivities in the neuritis model. The systemic administration of the HCN-specific blocker ZD7288 produced a reversal of heat but not mechanical hypersensitivity within one hour post-administration. Recordings from C-fiber neurons were performed to determine whether ZD7288 acts by inhibiting ongoing activity. ZD7288 (0.5mM) caused a 44.1% decrease in the ongoing activity rate following its application to the neuritis site. Immunohistochemical examination of the HCN2 channel subtype within the L5 dorsal root ganglia revealed an increase in expression in neuronal cell bodies of all sizes post-neuritis. In conclusion, HCN channels contribute to the development of neuritis-induced heat hypersensitivity and ongoing activity. Drugs that target HCN channels may be beneficial in the treatment of neuropathic pain in patients with nerve inflammation.

• Authors: N Richards, A Dilley
• Journal: Neuroscience (Neuroscience) Vol. 284 Pg. 87-98 (Jan 22 2015) ISSN: 1873-7544 [Electronic] United States
• PMID: 25290015 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Cardiotonic Agents
• Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
• Pyrimidines
• ICI D2788

Topics

• Action Potentials (drug effects)
• Analysis of Variance
• Animals
• Cardiotonic Agents (toxicity)
• Chi-Square Distribution
• Functional Laterality
• Ganglia, Spinal (cytology)
• Gene Expression Regulation (drug effects)
• Hot Temperature (adverse effects)
• Hyperalgesia (etiology, metabolism)
• Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels (metabolism)
• Male
• Nerve Fibers (pathology)
• Neural Conduction (drug effects)
• Neuritis (complications)
• Pain Threshold (drug effects, physiology)
• Pyrimidines (toxicity)
• Rats
• Rats, Sprague-Dawley
• Sensory Receptor Cells (drug effects, physiology)