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Inhibition of HCN channel activity in the thalamus attenuates chronic pain in rats.

Abstract
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability in both peripheral and central nerve systems. Emerging evidence indicates that HCN channels are involved in the development and maintenance of chronic pain. However, the impact of HCN channel activity in the thalamus on chronic pain has not been examined. In this report, we evaluated the effect on nociceptive behaviors after infusion of a HCN channel blocker ZD7288 into the ventral posterolateral (VPL) nucleus of the thalamus in rats with neuropathic pain or monoarthritis. We show that ZD7288 dose-dependently attenuated mechanical allodynia and thermal hyperalgesia in rats with chronic pain. In the thalamus, immunoreactivity of both HCN1 and HCN2 subunits was increased in both rat models. These results suggest that the increased HCN channel activity in the thalamus of the ascending nociceptive pathway contributes to both chronic neuropathic and inflammatory pain conditions.
AuthorsWeihua Ding, Zerong You, Shiqian Shen, Lucy Chen, Shengmei Zhu, Jianren Mao
JournalNeuroscience letters (Neurosci Lett) Vol. 631 Pg. 97-103 (Sep 19 2016) ISSN: 1872-7972 [Electronic] Ireland
PMID27542339 (Publication Type: Journal Article)
CopyrightCopyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Hcn1 protein, rat
  • Hcn2 protein, rat
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Potassium Channels
  • Pyrimidines
  • ICI D2788
  • Freund's Adjuvant
Topics
  • Animals
  • Arthritis, Experimental (physiopathology)
  • Chronic Pain (physiopathology)
  • Freund's Adjuvant
  • Hyperalgesia (physiopathology)
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels (antagonists & inhibitors, metabolism, physiology)
  • Male
  • Neuralgia (physiopathology)
  • Nociception (physiology)
  • Potassium Channels (metabolism, physiology)
  • Pyrimidines (administration & dosage)
  • Rats
  • Rats, Sprague-Dawley
  • Thalamus (metabolism, physiopathology)

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