Genetics are thought to play a major role in predisposing people to migraines. And in those who are predisposed, migraine attacks can occur spontaneously or be set off by a host of environmental factors, including stress, noise, bright lights, changes in sleep patterns and certain foods, as well as fluctuating estrogen levels, which may be why the disorder is about three times more common in women than in men.

But how these factors interact and the specific ways in which they exert an influence on neural processes are not well understood, said Dr. Dodick, who is involved in experimental work on occipital nerve stimulation and has served as a science adviser to Neuralieve.

Neurologists also do not know where in the brain a migraine begins and how additional areas are involved as the attack progresses, the details of which may be different for different patients.

Cortical-spreading depression may occur in some people, Dr. Dodick said. But other neural mechanisms are almost certainly at play, as well, and may turn out to be even more fundamental. Dysfunctional pain control centers in the brain stem may prove to be a root cause of the disorder, at least for some.

Nonetheless, he said, once the basic science of migraine is better understood, it will be possible to develop pharmaceuticals that aim to prevent attacks without untoward side effects. “That’s where I believe the future is.”

J. Steven Poceta, a neurologist at the Scripps Clinic in La Jolla, Calif., who is not involved in the current trials, also focused on the importance of new drug discoveries. Dr. Poceta emphasized that migraines are a progressive disorder, with headaches often becoming more frequent and less amenable to treatment. The goal, he said, is to develop drugs that can stop the progression before it gets to the point where nothing works.

“The brain is an organ that learns,” he said. “That’s its basic job. So the more it does something, the more it tends to do that same thing.”