When pain goes bad: Might glia be the culprit causing fibromyalgia pain?
Linda R. Watkins, PhD
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In chronic pain conditions, such as fibromyalgia, the assumption that is classically made is that neurons cause the problem. That is, the uncontrolled pain must be due to malfunctioning neurons in the pain pathway. I will offer a radically different view. That is, that non-neuronal cell types called glia may be the root of the problem. Spinal cord glia (astrocytes and microglia) are immune-like cells which release an array of neuroexcitatory substances when these cells are triggered to activate. Key among these spinally-released substances are the proinflammatory cytokines: Interleukin-1 (IL1), interleukin-6 (IL6) and tumor necrosis factor (TNF). Evidence accruing across multiple laboratories over the past decade provide compelling support that activated glia, and their proinflammatory cytokine products, are key players in the creation and maintenance of diverse pathological pain states. This profile suggests novel approaches to pain control where spinal cord glia and their proinflammatory cytokines are the therapeutic target, rather than neurons. In animal models, this strategy is clearly successful. A novel non-viral gene therapy approach (which constrains glial activation by driving the spinal production of the anti-inflammatory cytokine interleukin-10 [IL-10]), abolishes neuropathic pain for well over 3 months. Indeed, once pain eventually returns, complete pain relief is again readily re-instated by simple follow-up IL-10 therapy. While such an approach will hopefully reach clinical trials, it is clear that pharmaceutical companies are resistant to fibromyalgia as a target population, as there are no animal models to document whether spinal glial activation does or does not occur in this syndrome. A new human postmortem project will be described which aims to provide this missing key; that is, to define whether glial activation does indeed occur in spinal cords of fibromyalgia patients compared to pain-free controls. By registering donors for this ambitious program prior to death, thorough documentation of medical, drug, and pain histories will be available in addition to anatomical, mRNA and protein analyses of spinal tissues. It will be through such a program that the role of glia in fibromyalgia pain will begin to be clarified.
National Fibromyalgia Research Association
New and Future Directions in FM Pain Management
Symposium—Portland, OR—August 2004
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