Altered sodium channel expression in second-order spinal sensory neurons contributes to pain after peripheral nerve injury.

Abstract

Peripheral nerve injury is known to upregulate the rapidly repriming Na(v)1.3 sodium channel within first-order spinal sensory neurons. In this study, we hypothesized that (1) after peripheral nerve injury, second-order dorsal horn neurons abnormally express Na(v)1.3, which (2) contributes to the responsiveness of these dorsal horn neurons and to pain-related behaviors. To test these hypotheses, adult rats underwent chronic constriction injury (CCI) of the sciatic nerve. Ten days after CCI, allodynia and hyperalgesia were evident. In situ hybridization, quantitative reverse transcription-PCR, and immunocytochemical analysis revealed upregulation of Na(v)1.3 in dorsal horn nociceptive neurons but not in astrocytes or microglia, and unit recordings demonstrated hyperresponsiveness of dorsal horn sensory neurons. Intrathecal antisense oligodeoxynucleotides targeting Na(v)1.3 decreased the expression of Na(v)1.3 mRNA and protein, reduced the hyperresponsiveness of dorsal horn neurons, and attenuated pain-related behaviors after CCI, all of which returned after cessation of antisense delivery. These results demonstrate for the first time that sodium channel expression is altered within higher-order spinal sensory neurons after peripheral nerve injury and suggest a link between misexpression of the Na(v)1.3 sodium channel and central mechanisms that contribute to neuropathic pain after peripheral nerve injury.

• Authors: Bryan C Hains, Carl Y Saab, Joshua P Klein, Matthew J Craner, Stephen G Waxman
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 24 Issue 20 Pg. 4832-9 (May 19 2004) ISSN: 1529-2401 [Electronic] United States
• PMID: 15152043 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• NAV1.3 Voltage-Gated Sodium Channel
• Nerve Tissue Proteins
• Oligonucleotides, Antisense
• RNA, Messenger
• Scn3a protein, rat
• Sodium Channels

Topics

• Animals
• Behavior, Animal (drug effects, physiology)
• Disease Models, Animal
• Hyperalgesia (etiology, metabolism)
• Immunohistochemistry
• In Situ Hybridization
• Ligation
• Male
• NAV1.3 Voltage-Gated Sodium Channel
• Nerve Tissue Proteins (antagonists & inhibitors, genetics, metabolism)
• Neurons, Afferent (drug effects, metabolism)
• Oligonucleotides, Antisense (pharmacology)
• Pain (etiology, physiopathology)
• Pain Measurement (drug effects)
• Posterior Horn Cells (drug effects, metabolism)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Sciatic Neuropathy (complications, metabolism, physiopathology)
• Sodium Channels (genetics, metabolism)
• Spinal Cord (drug effects, metabolism)
• Up-Regulation