FINAL REPORT: Endogenous Opioid Mechanisms in Chronic Migraine

Summary

Chronic migraine patients were scanned during their spontaneous (not drug induced) attacks using positron emission tomography with a selective mu-opioid receptor radiotracer. Patients were gender and age-matched with healthy controls, and females were scanned during the same menstrual phase. There was an increase in mu-opioid neurotransmission in the thalamus of chronic migraine patients during the headache phase, which was significantly correlated with the combined severity of the headache attack’s area and intensity. This study shows, for the first time in vivo (in humans), a dysfunction in the endogenous (internal) mu-opioid system of chronic migraine patients. This system is arguably the most central mechanism associated with pain perception and modulation, and the main molecular target for opiate therapy.

Hypothesis vs. Findings

Our results confirmed that in response to clinical and experimental pain, there was high endogenous (internally occurring) opiod activation in the chronic migraineurs’ brains during headache attacks, which was correlated with the severity of the attack.

Unanswered Questions

The most important unanswered question is whether the thalamic mu-opioid mechanism can be directly modulated for experimental and clinical measures in chronic migraine. Unfortunately, exogenous opioids (administered externally) are unable to selectively target those dysfunctional brain regions without inducing multiple adverse effects, including worsening of the headache attacks. However, our recent studies have shown that modulation of such mu-opioid mechanisms can be accurately achieved using non-invasive brain stimulation. Our laboratory is currently developing novel neuromodulatory technologies and protocols for migraine, and is investigating their immediate and long-term effects in the brains of patients.

What This Research Means to You

These preliminary findings could explain the limitations of abortive opioid therapy for chronic migraine patients. While understanding central mechanisms in chronic migraine using molecular neuroimaging is important, equally important is developing novel concepts for future clinical application. This could be a change of paradigm in migraine research, as we directly investigate and modulate in vivo one of the most important endogenous (internally occurring) analgesic mechanisms in the brain.