Six-month postwithdrawal fMRI scans reveal pain matrix alterations corresponding to clinical improvements in patients who have chronic migraine with medication overuse.
STOWE, VT—Medication overuse in patients with chronic migraine appears to cause changes to the central pain matrix that contribute to the chronification of headaches, Gennaro Bussone, MD, reported at the Headache Cooperative of New England’s 20th Annual Headache Symposium. Through fMRI scans, Dr. Bussone and colleagues examined functional changes in supraspinal structures of the pain matrix in analgesic- and/or triptan-dependent migraineurs before and six months after medication withdrawal and found that postwithdrawal pain pathways resemble those of healthy control subjects.
“This is the first research with fMRI in this kind of headache,” Dr. Bussone told Neurology Reviews. “Our results confirm our hypothesis about the involvement of pain pathways and pain matrix in the pathophysiology of headaches.”
Dr. Bussone, Head of the Clinical Neurosciences Department at C. Besta National Neurological Institute in Milan, and colleagues recruited 13 women (mean age, 34) who, on average, had had migraines for 16 years, had 19 migraines a month, and had been overusing analgesics for 2.7 years. Eleven healthy women (mean age, 37) were the control group. Patients were given full neurologic and physical examinations, and they filled out the Migraine Disability Assessment (MIDAS) questionnaire; headache diary cards were provided to record headache days and analgesics intake per month.
All subjects and controls underwent a psychophysical testing session in which they rated mechanical pressure stimulation applied to a finger for three seconds, on one of three pain levels: noticeable, moderate, or strong.
Participants then underwent an fMRI scan, in which they were exposed to painful stimuli of varying levels for six seconds, pseudo-randomly presented in 18-second blocks to avoid adaptation and interspaced with 18-second blocks of baseline pressure.
The fMRIs revealed that the right supramarginal gyrus and the right inferior and superior parietal cortex were significantly less metabolically active in patients compared with controls. The researchers found no areas that had significantly higher activation or abnormal activation areas in the brainstem or hypothalamus in either group. These findings are consistent with previous research that reported central sensitization alterations in patients with chronic migraine.
After the initial fMRI was performed, the patients were admitted to an inpatient withdrawal program for six days. Patients were given a combination of IV steroids in low doses and benzodiazepines, a protocol typically used at Dr. Bussone’s clinic. After the patients completed withdrawal, they were given a migraine prophylaxis based on their history. Patients were seen every three months, and at six months nine of the patients underwent a second fMRI study.
“During the six months after medication withdrawal and the [first] scan, the mean number of headache days was significantly reduced,” Dr. Bussone reported. “The analgesic consumption was also significantly reduced. Moreover, the MIDAS score was significantly reduced from about 83 in the period preceding medication withdrawal to 32 after six months. This indicates a clinically significant decrease in disability levels.”
The researchers also found improvement in the pain matrix activity based on fMRIs taken six months after medication withdrawal. Compared with the first scan, the second fMRI showed a return to normal metabolic activity in the postwithdrawal state. These results corresponded with the clinical improvements as well.
“The hypometabolic areas are congruent with the brain regions belonging to the pain network,” Dr. Bussone explained. “We suggest that this hypoactivation we have detected in the lateral pain system, elicited by stimuli applied in regions far from where the headache is experienced, supports the hypothesis of a modification of the pain network and that these changes are consequences of the headache and and may contribute to its chronification.
“We can also speculate that this hypoactivity in medication over-users favors ongoing overuse and may be induced by the repeated drug intake,” he commented.