Functional upregulation of nav1.8 sodium channels on the membrane of dorsal root Ganglia neurons contributes to the development of cancer-induced bone pain.

Abstract

We have previously reported that enhanced excitability of dorsal root ganglia (DRG) neurons contributes to the development of bone cancer pain, which severely decreases the quality of life of cancer patients. Nav1.8, a tetrodotoxin-resistant (TTX-R) sodium channel, contributes most of the sodium current underlying the action potential upstroke and accounts for most of the current in later spikes in a train. We speculate that the Nav1.8 sodium channel is a potential candidate responsible for the enhanced excitability of DRG neurons in rats with bone cancer pain. Here, using electrophysiology, Western blot and behavior assays, we documented that the current density of TTX-R sodium channels, especially the Nav1.8 channel, increased significantly in DRG neurons of rats with cancer-induced bone pain. This increase may be due to an increased expression of Nav1.8 on the membrane of DRG neurons. Accordantly, blockade of Nav1.8 sodium channels by its selective blocker A-803467 significantly alleviated the cancer-induced mechanical allodynia and thermal hyperalgesia in rats. Taken together, these results suggest that functional upregulation of Nav1.8 channels on the membrane of DRG neurons contributes to the development of cancer-induced bone pain.

• Authors: Xiao-Dan Liu, Jing-Jing Yang, Dong Fang, Jie Cai, You Wan, Guo-Gang Xing
• Journal: PloS one (PLoS One) Vol. 9 Issue 12 Pg. e114623 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25503076 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• A 803467
• Aniline Compounds
• Furans
• NAV1.8 Voltage-Gated Sodium Channel
• Scn10a protein, rat
• Sodium Channel Blockers

Topics

• Aniline Compounds (pharmacology, therapeutic use)
• Animals
• Bone Neoplasms (complications)
• Cell Line, Tumor
• Cell Membrane (drug effects, metabolism)
• Electrophysiological Phenomena (drug effects)
• Female
• Furans (pharmacology, therapeutic use)
• Ganglia, Spinal (drug effects, pathology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Hyperalgesia (drug therapy, etiology)
• NAV1.8 Voltage-Gated Sodium Channel (metabolism)
• Neurons (drug effects, pathology)
• Pain (drug therapy, etiology, metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Sodium Channel Blockers (pharmacology, therapeutic use)
• Up-Regulation (drug effects)