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Another potential target is the KCC2 transporter on spinal-cord neurons. One of the characteristics of chronic pain is an increased concentration of chloride ions in neurons, which causes them to fire in a hyperexcited manner. Because a normal-functioning KCC2 removes chloride from the cells, something happens in chronic pain that causes the KCC2 to down-regulate and allow for a rise in chloride concentration. We've shown that both the activation of P2X4 and the rise in intracellular chloride concentrations are necessary for maintaining chronic pain.
In addition to finding new approaches to treating chronic pain, we need better ways of diagnosing it. Individuals with intractable pain often stop talking about their problem because few people believe them. It's no surprise, then, that many patients with this condition become depressed and may even begin to prefer the thought of death to living with their intense pain. An objective diagnostic test would allow people with neuropathic pain to say “my microglia cells are activated” or “the chloride concentration in my spinal neurons is too high,” much as we cite cholesterol or glucose readings now. Being able to point to a physiological difference would allow patients suffering from chronic pain to gain legitimacy and, as a consequence, merit higher priority among medical practitioners, researchers, and the public.
The work in our lab might help with that problem. By quantifying the physiological changes involved in chronic pain, we may be able to create assays to measure microglia activation or a change in chloride-ion concentration.
Our goal is that this research will ultimately lead to viable therapeutic options as well.
A physician-scientist, Michael Salter received his M.D. from the University of Western Ontario and his Ph.D. from McGill University.
Interview by Amy Stone