A series of three research papers by a team in France attempted to determine how abnormalities in brain blood flow in fibromyalgia (FM) patients is related to various pain processing centers, the patient’s pain level, and their response to ketamine. Ketamine is an anesthetic pain reliever that also blocks the NMDA receptors that magnify pain. Some FM patients will respond dramatically to ketamine, while it does not even dull the pain for others. These studies, headed up by Eric Guedj, M.D., sought to find out what ketamine does in the brain to produce pain relief and if there are blood flow differences in patients who do not respond to the drug.All three studies used single-photon emission computed tomography (SPECT) technology to image the brains of 17 FM women and 10 healthy control women.¹ These same subjects were used throughout the three studies, and one should keep in mind that the FM patients were selected because their pain was severe. Although previous reports have shown decreased blood flow to a few areas in the brain, Guedj’s team chose to use a newly developed intravenously injected tracer that more accurately illuminates blood flow in areas deep within the brain.

FM versus Healthy Controls

Comparison of the FM group with the healthy subjects showed that there were many significant differences in blood flow patterns based on their brain SPECT scans. FM patients had hyperperfusion (enhanced blood flow) to several areas in the outer layers of the sensory cortex. The sensory cortex is responsible for determining where the pain is located and estimating how much it hurts. The increased blood flow to the sensory cortex in FM patients means that this area is very active in processing the bombardment of incoming noxious/pain signals. The pain of FM is clearly visible on the SPECT scans.

Ordinarily, lots of activity in the outer sensory cortex should lead to activation of the other pain processing centers that are located deeper within the brain. However, the opposite was found for patients with FM. Compared to the healthy subjects, the FM group had reductions in blood flow (meaning less activity) in the medial frontal lobe, the anterior and posterior cingulate, the cerebellum, the amygdala, portions of the hippocampus, the thalamus, the caudate nucleus, and regions located all the way down in the brain stem. So while the sensory cortex is being overloaded with pain signals, the other pain processing centers in the brain are under-performing and it is no wonder why FM patients experience serious pain.

Identifying Ketamine Responders

The second study looked at the brain SPECT scans before and after the subjects were given an intravenous infusion of ketamine.² Eleven of the 17 FM patients responded with a 50% or more drop in pain scores, but six did not respond. Looking at the SPECT scans prior to ketamine, the research team found a difference between the patients who responded to the drug and those who didn’t. People who did not respond had a greater decrease in blood flow in the center portion of their frontal lobe than those who found relief with ketamine. The center area of the frontal lobe is important for regulating the brain’s response to pain.

Ketamine’s Effect on Brain Blood Flow

What does ketamine do to the brain’s blood flow to cause a significant reduction in pain? This was the question asked and answered by the third study.³ The SPECT scans showed that ketamine did not alter the hyperactivity in the outer sensory cortex, but it did increase the blood flow to the deeper pain processing structures in the brain. In fact, the greater the increased blood flow produced by ketamine, the greater the patient’s pain relief. For patients who do not respond to ketamine, it just means that their pain may be more strongly driven by malfunctions of other areas in the brain that ketamine does not influence (such as the center portion of the frontal lobe).

Does this mean you should try ketamine? Not necessarily. Ketamine can be formulated into a nasal spray, but its use is limited by its side effects and doctors do not generally prescribe it. Instead, you may try a related drug, dextromethorphan. It is available in cough syrups, but to effectively dose up to amounts that have been shown to be beneficial in FM patients, you may want to ask your doctor for a prescription to get the drug compounded. No one sells oral tablets or capsules of dextromethorphan, so it must be prepared at a compounding pharmacy. One study showed that the average effective dose for FM patients was 150 mg/day (i.e., 50 mg three times a day). However, you should probably start with 25 mg capsules and dose up slowly to minimize side effects.

1. Guedj E, et al. Eur J Nuc Med Mol Imaging 34:130-4, 2007.
2. Guedj E, et al. Eur J Nuc Med Mol Imaging 34:1274-9, 2007.
3. Guedj E, et al. Eur J Nuc Med Mol Imaging 34:2115-9, 2007.

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