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 sodium ion channel, Nav1.8, that is selectively expressed in primary afferent neurons (especially nociceptors) ameliorate reflex hypersensitivity and pathological pain-related motivational/cognitive alterations caused by traumatic spinal cord injury (SCI). The first phase of the project has largely been accomplished, with a major paper published describing how effective antisense knockdown of Nav1.8 eliminates SCI-induced spontaneous activity in nociceptors, reverses mechanical and heat hypersensitivity of hindlimb withdrawal reflexes, and ameliorates ongoing, spontaneous pain. It was also found that SCI upregulated Nav1.8 protein without upregulating Nav1.8 mRNA, either in the DRG or spinal cord. Additional results showed that a selective Nav1.8 antagonist, A-803467, reverses heat hypersensitivity and may attenuate mechanical hypersensitivity. Unexpected results indicate that below-level cutaneous hypersensitivity after SCI is not translated into motivational/cognitive components of evoked pain. On the other hand, it was demonstrated for the first time in any animal model that SCI enhances anxiety behavior. Preliminary results support the exciting possibility that Nav1.8-dependent hyperactivity in primary nociceptors not only promotes hyperreflexia, spontaneous pain, and evoked pain, but also anxiety after SCI.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2014
- Accession Number
- ADA624311
Entities
People
- Edgar Walters
Organizations
- University of Texas Health Science Center at Houston