Rats with migraines provide Jefferson scientists insights to improved drug strategy

When Michael Oshinsky, Ph.D., gives his rats a headache, he has good reason.

The animals are helping Dr. Oshinsky, assistant professor of neurology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, study how migraine treatments work. In recent experiments, the animals provided evidence showing that DHE, a standard drug currently used to treat acute migraine pain can also work against the onset of a phenomenon called “central sensitization,” or “allodynia,” which involves, as most migraine sufferers know, a heightened sensitivity to touch. He presents his findings April 12, 2005 at the annual meeting of the American Academy of Neurology in Miami Beach.

For many migraine sufferers, it hurts to touch their face, brush their hair, even take a shower during a migraine attack. Triptans, another class of drugs commonly used to treat migraines, can also treat acute headache pain, but has a narrow window in which it works against allodynia. Dr. Oshinsky looked at DHE’s effectiveness on halting or lessening this secondary effect.

According to Dr. Oshinsky, putting various chemicals – “inflammatory mediators” such as bradykinins and prostaglandins – on the dura, the outside covering of the brain, causes local inflammation and activates the sensory fibers that cause pain on the dura. Neurons in a brain region called the trigeminal nucleus caudalis are then activated, setting off the sensitization process. Stimulating this pathway in the brain is a model for studying the effects of migraine drugs.

Dr. Oshinsky treated animals with DHE before, during and after giving the animals a headache. By recording the change in the activity of the neurons in the brain, he can monitor the effects of medication on the induced headache. He found that pretreating with DHE, and treating with DHE at the beginning of the induced headache prevents the headache from progressing to the debilitating sensitization state.

“Physicians have used intravenous DHE as a standard treatment for patients admitted to the hospital for their migraines,” Dr. Oshinsky notes. “The data in this new study suggest that more patients can benefit from this treatment. Since most migraine sufferers typically delay treatment until the pounding in their head has spread to their forehead or around their eyes, at this stage they don’t respond well to most treatments. These data suggest that treatment with DHE can reverse this sensitization.”

Dr. Oshinsky would like to better understand which neurotransmitters are involved in sensitization, which he hopes will lead to the development of improved migraine drugs.