Why do those with fibromyalgia often experience nerve pain?
Science: Pro-inflammatory cytokines trigger NF-kappaB activation leading to enhanced pain transmission.
Conclusion: Pro-inflammatory cytokine excess may be responsible for the neuropathic pain of fibromyalgia.
Nerve pain represents a substantial component of total fibromyalgia pain.
It’s likely that pain in fibromyalgia syndrome is of several different types. Fibromyalgia patients not infrequently report burning, tingling or sometimes stabbing pain characteristic of neuropathic pain. This pain is unique from the diffuse pain (“aching”) that is also reported by most with fibromyalgia.
Neuropathic pain is commonly thought to result from nerve damage, but the actual cause of neuropathic pain remains unknown. Of interest, neuropathic pain was formerly referred to as ‘non-inflammatory’ pain, but recent evidence has shown that inflammation plays a critical role in the onset and progression of all pain, including neuropathic pain.
Neuropathic pain may result from NF-kappaB activation by cytokines, especially IL-8.
How might neuropathic pain arise in fibromyalgia syndrome? Perhaps in part as the result of excess cytokine production.
The study briefly summarized below discusses pro-inflammatory cytokines. It was observed that pro-inflammatory cytokines in and around the spinal cord can turn on NF-kB. NF-kB is something like an inflammation ‘master switch’. As a result of NF-kB activation, cells ‘turn on’ inflammation and begin generating mediators of inflammation, including more cytokines. The net result, the authors conclude, is neuropathic pain. So at least some neuropathic pain might be attributed to cytokine activation of NF-kB in and around the spinal cord.
That might explain neuropathic pain in fibromyalgia, because cytokines, especially IL-8, are consistently elevated in those with fibromyalgia. At least six studies document elevated IL-8 in those with fibromyalgia (one study found normal levels.) Further, at least three studies have shown a direct correlation between the level of IL-8 and pain severity.
While IL-8 is not specifically mentioned in the abstract, IL-8 is a pro-inflammatory cytokine that is known to activate NF-kB. And it is NF-kB activation that the authors suggest is responsible for generating neuropathic pain.
1. Pro-inflammatory cytokine levels (especially IL-8) are elevated in fibromyalgia.
2. Pro-inflammatory cytokines (including IL-8) turn on NF-kappaB.
3. NF-kappaB activation in and around the spinal cord appears to play a significant role in generating neuropathic pain.
Therefore it’s likely that pro-inflammatory cytokine excess is largely responsible for the neuropathic pain of fibromyalgia.
What’s the solution?
Inhibition of NF-kB should lead to an immediate reduction in neuropathic pain. And, because it was excess activation of NF-kappaB that led to pro-inflammatory cytokine excess in the first place (can you see the vicious cycle?) – inhibiting NF-kB should provide a long-term benefit by lowering pro-inflammatory cytokine levels.
We get twice the pain killing power by going after NF-kB. That’s good. We need all the pain killing power we can get.
Involvement of spinal cord nuclear factor kappaB activation in rat models of pro-inflammatory cytokine-mediated pain facilitation.
Summary of the abstract
Pro-inflammatory cytokines, such as IL-1 and TNF are released by activated cells in the spinal cord and play a major role in pain.
Those cytokines exert their actions, at least partially, through the activation of the transcription factor, nuclear factor kappaB (NF-kappaB). In turn, NF-kappaB regulates the transcription of many inflammatory mediators, including more cytokines.
This study investigated whether NF-kappaB is involved in neuropathic pain induced by sciatic nerve inflammation.
The results of the study demonstrated that spinal cord NF-kappaB activation plays a role in exaggerated pain states.