February/March 2026 Clinical Research Update: The Latest Findings in Migraine – Part 1

Recent research shows successes and challenges for the migraine field.

Editor’s note: This two-part article is the latest installment of our periodic coverage of select new clinical studies in the migraine and headache field. What follows below is Part 1. (See Part 2 here).

Changes in neurometabolites linked to migraine in kids
A small longitudinal study in children and adolescents recently examined potential alterations in brain chemistry over time in this population, and whether those changes might be associated with the progression of migraine.

The focus was on glutamate, the brain’s primary excitatory neurotransmitter, and gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. Previous evidence has suggested that changes in the balance of excitation and inhibition in the brain could underlie migraine, with changes in glutamate and GABA levels being prime candidates to serve this role.

The study, published in Scientific Reports, included 22 participants with migraine, and 15 controls, all between the ages of 7 and 17. The researchers measured glutamate and GABA levels using magnetic resonance spectroscopy, a type of magnetic resonance imaging technique that allows for measurement of brain metabolites. The study included participants from previous pediatric migraine imaging studies who underwent a second magnetic resonance imaging scan at a second visit. All participants completed headache questionnaires at the first and second visits.

The researchers were particularly interested in measuring neurotransmitter levels in the sensorimotor cortex, which is involved in pain and sensory processing; the occipital cortex, which is involved in visual processing and aura; and the thalamus, known as the “relay station” of the brain for its role in routing sensory information from the peripheral nervous system to the cortex of the brain.

The study’s main finding was a decrease in thalamic GABA levels over time in participants who previously did not have migraine but would go on to develop it (new onset migraine) between the two study visits, a decrease that was also associated with worsening migraine disability. Some differences in other metabolites, including creatine and choline, were also observed, with those with new onset migraine, and those with an initial migraine diagnosis, showing lower levels, compared to controls. Glutamate levels did not change over time in any of the brain regions examined in the study, in any of the groups.

The authors note important limitations of the study, including the small sample size of the migraine and control groups, and caution that it is preliminary work. Still, “[t]o our knowledge,” they wrote, “there are no other studies that have investigated neurochemical changes during adolescence and the relationship to migraine burden. Therefore, though our results are preliminary in nature, they provide unique knowledge about migraine progression and can guide future studies of this nature.”

Encouraging results from an anti-PACAP trial
Though detailed data have not been made available yet, the biopharmaceutical company Lundbeck recently issued a press release reporting top-line results of a clinical trial of bocunebart, a monoclonal antibody directed against pituitary adenylate cyclase-activating polypeptide (PACAP), for migraine prevention. Hoping to build upon the success of anti-calcitonin gene-related peptide (CGRP) therapy, the migraine field has been looking for its next treatment success, and the new results help build the case that PACAP, a neuropeptide linked to migraine pathophysiology, could be a successful target for migraine therapy.

The company reported that intravenous bocunebart produced a statistically significant, greater change from baseline in the number of monthly migraine days, the study’s primary endpoint, compared to placebo, over weeks 1 to 12 of the study. This Phase IIb trial, called PROCEED, included people who had experienced one to four previous preventive treatment failures over the past decade.

The press release stated that “[t]hese data build on findings from the previously successful HOPE phase IIa trial evaluating single IV administration of bocunebart.”

Previous clinical and animal data suggest that the PACAP and CGRP systems are largely independent of one another. This means that anti-PACAP therapy could perhaps help those who have not responded sufficiently to anti-CGRP antibodies.

New data to support rimegepant use in an underrepresented population
Many clinical trials of migraine drugs have reported the effectiveness of anti-CGRP therapies. However, those investigations have primarily included White people, with other groups, including Black or African American individuals, drastically underrepresented. This is a highly problematic issue for a host of reasons, including that Black or African American people experience migraine at rates similar to those seen in White populations yet are less likely to seek help from healthcare providers, receive a migraine diagnosis, and receive prescription migraine treatment.

A new study published in Headache now provides much-needed data in this regard, reporting that rimegepant, a CGRP receptor antagonist, is safe and effective for Black or African American individuals with migraine.

The researchers pooled data from three randomized trials of rimegepant that were based in the United States; the trials were focused on acute treatment of a single migraine attack. The pooled population for this post hoc subgroup analysis included more than 3,500 people, with nearly 20% of participants from the Black or African American population. The results indicated that rimegepant was effective in Black or African American study participants on the trials’ co-primary endpoints of freedom from pain, and freedom from most bothersome symptom (MBS), two hours after drug administration.

Specifically, 24.4% of Black or African American participants reported pain freedom at two hours, compared to 18.2% of the placebo group, equating to a risk difference of 6.2%. A risk difference versus placebo of 7.6% was observed for MBS freedom. These risk differences were similar to those seen in White participants. Further, for five out of 11 secondary endpoints, rimegepant showed statistically significant improvement versus placebo in Black or African American participants, compared to 10 of 11 in White participants; differences on these endpoints tended to be smaller for Black or African American participants. Finally, the overall adverse event profile was similar between Black or African American participants and White participants.

In their discussion, the authors wrote that while the effect sizes for Black or African American participants tended to be lower compared to White participants, this could partly be due to small sample sizes, even with the pooling of the three studies that made up the analysis.

The impact of pain on memory
In an interesting study published in Brain Communications, researchers investigated the effects of pain on memory, including in a group of 55 people with chronic migraine, 59 with chronic back pain, and 59 age-matched healthy controls. Since people who have pain often report cognitive difficulties, the researchers expected to see detrimental effects of pain on cognition. To their surprise, that was not the case, at least in terms of effects on memory.

The investigators electrically stimulated the forehead or lower back to induce experimental pain. As they were receiving the stimulation, study participants completed a visual categorization task in which they had to categorize images of objects as either living or non-living objects. After that, to see how pain may have affected memory, subjects completed a recognition task where they saw all the images from the categorization task, but also new images as well, and were then asked whether the images they were seeing were old (previously seen), or new (unseen).

The researchers found that there were no differences among the three groups in correctly categorizing the images as living or non-living. The site of painful stimulation in the patient groups (forehead or lower back) also made no difference. And the type of pain the patients had (migraine or low back pain) had no effect, either.

Similarly, there were no differences among the healthy control, migraine, and low back pain groups on the subsequent recognition task – all groups showed impaired recognition. Further, here, too, there were no differences based on the site of electrical stimulation, nor did the type of pain the patients had play a role. The investigators also saw that, in the pain patients, various clinical parameters like clinical pain intensity or pain frequency, beliefs about pain, and psychological variables, had only a marginal effect on performance of the recognition task.

Interestingly, the results indicated that the head pain condition did not cause greater disruption of recognition memory relative to the back pain condition, including for the migraine group. In fact, it was the opposite for those with migraine, as they performed better on the recognition task when they had received electrical stimulation at the head compared to stimulation at the back. This was contrary to expectations, the researchers said, since previous research had suggested that stimulation of the trigeminal system, thought to be more biologically relevant to pain, would have a greater effect on cognition than stimulation at other body sites.

Importantly, there were some differences for other cognitive factors, with migraine patients showing reduced verbal flexibility, and the back pain patients showing poorer divided attention, compared to the control group.

“These findings suggest that chronic pain may not uniformly affect all cognitive domains but instead preferentially impacts executive and attentional control systems. Thus, the lack of group differences in pain-induced recognition memory should not be interpreted as an absence of cognitive consequences of chronic pain; rather, it points to differential vulnerability of cognitive domains, with executive and attentional processes more affected than episodic memory encoding in acute laboratory conditions.”

The researchers also noted that there is much variability among individuals in how pain affects memory, so they recommend additional studies beyond group-level analyses to get a better handle on this issue.

See Part 2 here.

Neil Andrews is a science journalist and executive editor of the Migraine Science Collaborative.

Image credit: 123RF Stock Photo/ID: 141848843