Novel Target for Ameliorating Pain and Other Problems after SCI: Spontaneous Activity in Nociceptors
Abstract
The purpose of the project is test the hypothesis that interventions that reduce the function of a Na+ ion channel, Nav1.8, that is selectively expressed in primary afferent neurons (especially nociceptors) ameliorate chronic pain and reflex hypersensitivity caused by traumatic spinal cord injury (SCI). The first phase of the project has largely been accomplished, despite several problems that had to be solved. Major results were a confirmation that Nav1.8 protein expression is selectively knocked down by intrathecal injection of antisense oligodeoxynucleotides targeting Nav1.8 mRNA, and demonstrations that this knockdown results not only in a reversal of mechanical and heat hypersensitivity of hindlimb withdrawal reflexes after SCI, but also in significant amelioration of ongoing, spontaneous pain. The existence of spontaneous pain in rodents after traumatic SCI and its dependence on Nav1.8 function were shown for the first time, using an operant conditioned place preference paradigm and an analgesic, retigabine, known to potently suppress electrical activity in primary nociceptors. These results suggest a promising new approach to treat SCI pain.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA599497
Entities
People
- Edgar Walters
Organizations
- University of Texas Health Science Center at Houston