Nav1.7 accumulates and co-localizes with phosphorylated ERK1/2 within transected axons in early experimental neuromas.

Abstract

Peripheral nerve injury can result in formation of a neuroma, which is often associated with heightened sensitivity to normally innocuous stimuli as well as spontaneous dysesthesia and pain. The onset and persistence of neuropathic pain have been linked to spontaneous ectopic electrogenesis in axons within neuromas, suggesting an involvement of voltage-gated sodium channels. Sodium channel isoforms Na(V)1.3, Na(V)1.7 and Na(V)1.8 have been shown to accumulate in chronic painful human neuromas, while, to date, only Na(V)1.3 has been reported to accumulate within experimental neuromas. Although recent evidence strongly support a major contribution for Na(V)1.7 in nociception, the expression of Na(V)1.7 in injured axons within acute neuromas has not been studied. The current study examined whether Na(V)1.7 accumulates in experimental rat neuromas. We further investigated whether activated (phosphorylated) mitogen-activated protein (MAP) kinase ERK1/2, which is known to modulate Na(V)1.7 properties, is co-localized with Na(V)1.7 within axons in neuromas. We demonstrate increased levels of Na(V)1.7 in experimental rat sciatic nerve neuromas, 2weeks after nerve ligation and transaction. We further show elevated levels of phosphorylated ERK1/2 within individual neuroma axons that exhibit Na(V)1.7 accumulation. These results extend previous descriptions of sodium channel and MAP kinase accumulation within experimental and human neuromas, and suggest that targeted blockade of Na(V)1.7 or ERK1/2 may provide a strategy for amelioration of chronic pain that often follows nerve injury and formation of neuromas.

• Authors: Anna-Karin Persson, Andreas Gasser, Joel A Black, Stephen G Waxman
• Journal: Experimental neurology (Exp Neurol) Vol. 230 Issue 2 Pg. 273-9 (Aug 2011) ISSN: 1090-2430 [Electronic] United States
• PMID: 21601570 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• NAV1.7 Voltage-Gated Sodium Channel
• Scn9a protein, rat
• Sodium Channels
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Animals
• Axons (metabolism)
• Blotting, Western
• Immunohistochemistry
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• NAV1.7 Voltage-Gated Sodium Channel
• Neuroma (metabolism)
• Peripheral Nervous System Neoplasms (metabolism)
• Phosphorylation (physiology)
• Rats
• Rats, Sprague-Dawley
• Sciatic Nerve (metabolism)
• Sciatic Neuropathy (metabolism)
• Sodium Channels (metabolism)