Salmon Thrombin as a Treatment to Attenuate Acute Pain and Promote Tissue Healing by Modulating Local Inflammation
Abstract
The objectives of this project are to quantitatively define the biochemical and cellular mechanisms by which salmon thrombin may be responsible for alleviating pain. Work during the project period utilized biochemical, in vitro, and in vivo approaches to understand and define how human and salmon thrombin differ enzymatically and in modulating cellular inflammatory responses. We established relevant culture systems for making these assessments in astrocytes and mixed cultures and determined that salmon thrombin can reduce astrocytic activation, cytokine production, and not modify cellular mechanics. Substrates were identified for defining cleavage rates of PARs and comparisons between human and salmon thrombin revealed that salmon thrombin cleaves PAR1 at a significantly slower rate than human thrombin does. Our data suggest this may be due the lower affinity for hirudin. PAR1 is decreased in pain states, differentially based on the type of neural trauma and in association with the absence of pain. Early cleavage of PAR1 by thrombin may provide its anti-nociceptive properties. We were very productive, having met all of the milestones that were laid out in the approved statement of work. We have reported findings in presentations and manuscripts and are also poised to continue these investigations having proven our initial hypothesis that salmon thrombin has different properties from other species and that those properties confer tremendous potential for pain relief and tissue healing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2012
- Accession Number
- ADA579110
Entities
People
- Beth A. Winkelstein
Organizations
- University of Pennsylvania