Back pain, disc damage & NF-kappaB

Degenerating discs cause back pain as a result of inflammation resulting from NF-kappaB activation

Stopping inflammation is the key to eliminating discogenic back pain

In this study the effects of peroxynitrite are reviewed. We’re told that it’s an important tissue damaging compound that is generated at sites of inflammation and disc degeneration.

We’re not told to what extent the peroxynitrite results from inflammation vs. to what extent it causes the inflammation. It could both cause and result from inflammation, as is often the case with mediators of inflammation. The ‘species’ causes damage/inflammation AND stimulates further inflammation. A vicious cycle. Sometimes, for no obvious reason, inflammation cannot ‘turn off.” The result is chronic inflammation and pain that continues to worsen over time.

We are told they observed “sustained NF-kB translocation” which means NF-kB was chronically turned on. That is exactly what we would expect in chronic inflammation. The Master Switch remains stuck in the “on” position.

We are also told that high levels were observed for various mediators of inflammation – IL-1, IL-6 and IL-8. This is also what would be expected to observe when NF-kB is chronically turned on.

The researchers conclude by observing that NF-kB is the “potential” underlying pathway and suggest that back pain might be effectively treated with anti-oxidants.

It seems clear, however, that NF-kB is more than just the “potential” underlying pathway – it is clearly the reason for the inflammation. Rather than attempting to neutralize peroxynitrite with anti-oxidants, a better solution, it seems, would be to go “upstream” to the source. Inhibition of the source, NF-kB, would be a more effective anti-inflammation strategy than trying to limit one of the many pro-inflammatory species observed in this study of discogenic back pain.

The publication:

May, 2009

Peroxynitrite induces gene expression in intervertebral disc cells

Summary of the abstract

Peroxynitrite is an important tissue-damaging species generated at sites of inflammation and degeneration. The aim of this study was to examine the effects resulting from peroxynitrite.

Degenerated human intervertebral disc (IVD) tissue was analyzed for nitrosylation. Nitrosylation, accumulation of intracellular reactive oxygen species, NF-kappaB nuclear translocation, and cell viability were analyzed. Gene expression of TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10 was quantified.

Degenerated IVD tissue showed strong nitrosylation, especially in the NP. NF-kappaB/p65 sustained nuclear translocation of NF-kappaB/p65 and stimulation of IL-1beta, IL-6, and IL-8 expression was noted.

This study provides evidence that peroxynitrite may play a role in disc degeneration and discogenic back pain development by the increased synthesis of proinflammatory cytokines that results from the activation of NF-kB. Neutralizing peroxynitrite and its derivatives (e.g., via the use of antioxidants) may be a novel treatment option for discogenic back pain.


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