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Unraveling the chronic pain state


Phoenix Rising Founder
: Trends Neurosci. 2009 Sep 23. [Epub ahead of print]
Critical role of nociceptor plasticity in chronic pain. Reichling DB, Levine JD.


They seem to be making quite a bit of progress in understanding chronic pain (and one hopes that this will give them an insight into chronic fatigue as well!).

This is so interesting. The Dubbo group has shown that people who come down with ME/CFS after an infection tend to have abnormally high cytokine levels during the infection.

Here we have a paper stating an 'inflammatory insult' or 'environmental stressor' can trigger 'long-lasting hypersensitivity' of the nerve receptors for pain; they essentially flip on the pain switch in the nerves sending pain signals to the brain.

(This suggests the problem is not in the brain as many have suggested that the nerves sending signals to the brain. Yes, the brains pain producing pathways are overly activated - but they're activated by the problems in the nerves in the body. Interestingly Dr. light somewhat similar thesis for ME/CFS; the receptors for muscle damage are way over sensitized in ME/CFS - they are continuously sending pain and fatigue signals to the brain. )

The transition from acute to chronic pain states might be the most important challenge in research to improve clinical treatment of debilitating pain. We describe a recently identified mechanism of neuronal plasticity in primary afferent nociceptive nerve fibers (nociceptors) by which an acute inflammatory insult or environmental stressor can trigger long-lasting hypersensitivity of nociceptors to inflammatory cytokines.

This phenomenon, "hyperalgesic priming," depends on the epsilon isoform of protein kinase C (PKCvarepsilon) and a switch in intracellular signaling pathways that mediate cytokine-induced nociceptor hyperexcitability. We discuss the impact of this discovery on our understanding of, and ultimately our ability to treat, a variety of enigmatic and debilitating pain conditions, including those associated with repetitive injury, and generalized pain conditions, such as fibromyalgia.

They even think they know how this happens; protein kinase C. - which controls the signaling pathways - appears to flip the system into a hypersensitive state. Essentially it sounds like a system which should be turned on during an injury -stays on.

This is the biochemistry of chronic pain! When they get down to things like signaling molecules specific pathways you get the feeling that they may be getting close. Very hopeful stuff!