Spinal cord injury is often followed by increased pain perception. There is both immediate gross inflammation and chronic micro-inflammation.
Treatment with an NF-kB ‘decoy’ effectively blocks (inhibits) NF-kB activation, and was shown to improve outcome after spinal cord injury. Inflammation and pain were reduced, and an increase in GABA neurotransmitter was evidenced.
Nuclear factor-kappaB decoy amelioration of spinal cord injury-induced inflammation and behavior outcomes.
Summary of the abstract
Spinal cord injury (SCI) results in a pathophysiology that includes altered nociception (pain perception) and hyperalgesia (lower pain threshold and increased pain sensation). SCI triggers an early and prolonged inflammatory response, with increased interleukin-1beta levels.
Transient changes are observed in NF-kappaB.
There were significant early increases in COX-2 and inducible nitric oxide synthase after SCI.
We used synthetic double-stranded “decoy” deoxyoligonucleotides containing selective NF-kB protein dimer binding consensus sequences. Decoys targeting the p65/p50 binding site on the COX-2 promoter decreased SCI-induced cell losses, NF-kappaB p65/p50 DNA-binding activity, and COX-2 and iNOS protein levels. NF-kappaB p65/p50 targeted decoys improved early locomotor recovery after moderate but not severe SCI, yet ameliorated SCI-induced hypersensitization after both moderate and severe SCI.
To determine whether changes in GABA activity played a role in decreased hypersensitivity after SCI and p65/p50 targeted decoy, we counted gamma-aminobutyric acid (GABA)-containing neurons in laminae 1-3. There were significantly more GABAergic neurons in the p65/p50 targeted decoy-treated group at the level of injury.