Migraine and the Mu-opioidergic system-Can we directly modulate it? Evidence from neuroimaging studies

Migraine is a chronic trigeminal pain condition that affects the daily lives of a large part of our population. Its debilitating headache attacks, with increased sensitivity to multiple forms of stimuli, force many patients to rely on over the counter analgesics and resort to abuse of prescription medications, particularly opioid agonists. In the latter case, the indiscriminate medication-driven activation of the opioid system can lead to undesired side effects, such as the augmentation of hyperalgesia and allodynia, as well as the chronification of the attacks. However, we still lack information regarding the impact of migraine attacks and their relief on the function of μ-opioid receptor (μOR) mediated neurotransmission, the primary target of opioid medications. This line of inquiry is of particular importance as this neurotransmitter system is arguably the brain's most important endogenous mechanism involved in pain regulation, and understanding this endogenous mechanism is crucial in determining the effectiveness of opioid medications. Recently, new advances in molecular neuroimaging and neuromodulation have provided important information that can elucidate, in vivo, the role of the endogenous opioid system in migraine suffering and relief.