Neurochemical Imaging and Chronic Pain

The field of neurochemical imaging in pain is largely in its infancy. Very few studies have used this method to get at neurotransmitter levels or molecular information in the brain. MRI magnets can be used to detect changes in the way that protons behave in different molecules. So protons and the neurotransmitter glutamate behave differently from the protons that are in GABA, another neurotransmitter. What the MRI magnet is able to do is to perturb the activity of those protons, the magnetic properties of those protons, and as they relax back to their normal state, they give a signature output which looks like a spectra. This technique is called magnetic resonance spectroscopy.

We did a study about eight years ago showing that fibromyalgia patients had increases in glutamate specifically within the brain area that's involved in pain processing, the posterior insula. We found was that the patients with more glutamate in that area had increased sensitivity to painful stimuli. We then asked could this glutamate be a marker for some chronic pain disorders, and could it be a marker for treatment efficacy? So we decided to look at pregabalin, which is efficacious in fibromyalgia. We know that it inhibits clinical pain in fibromyalgia patients, so we examined if we give patients with fibromyalgia pregabalin, does it change their glutamate levels in the posterior insula. And we actually found that to be the case. We found that pregabalin actually reduced the concentration of glutamate in the posterior insula in fibromyalgia patients compared to others taking a placebo pill. Also the patients that had higher levels of the glutamate before treatment were more likely to respond to the drug pregabalin compared to placebo.

That has led me and others think that we might be able to use this neuroimaging approach to examine the glutamatergic mechanism, and identify patients who might be good candidates for a compound that affects it. Additionally, it could be a useful tool in the process of new drug discovery. For example, if we are developing a compound and that might be acting on the glutamatergic system of the brain, we could easily run a few patients through an imaging study to determine if your compound might be active or not. It gives us a good tool to say, "No, I don't think I should go down this path," or "Yes, maybe I should continue on pursuing this compound." You can't access that type of information noninvasively in humans.