Pathophysiology of medication overuse headache--an update

Area of Science:

• Neuroscience
• Pharmacology
• Headache Medicine

Background:

• The exact cause of medication overuse headache (MOH) remains unclear.
• Clinical and preclinical research indicates heightened neuronal excitability in the cerebral cortex and trigeminal system following medication overuse.
• This hyperexcitability is hypothesized to underlie MOH pathogenesis.

Purpose of the Study:

• To elucidate the neurobiological mechanisms contributing to medication overuse headache.
• To explore the role of central modulatory systems, such as serotonin (5-HT) and endocannabinoids, in MOH.
• To investigate the link between cortical and trigeminal system changes and pain perception in MOH.

Main Methods:

• Review of clinical and preclinical studies on medication overuse headache.
• Analysis of neurophysiological changes, including cortical excitability and trigeminal system activation.
• Examination of the involvement of neurotransmitter systems, particularly serotonin (5-HT) and endocannabinoids.

Main Results:

• Medication overuse leads to increased cortical and trigeminal neuronal excitability.
• Cortical hyperexcitability may promote cortical spreading depression, analogous to migraine aura.
• Derangements in serotonin (5-HT) and other modulatory systems, including reduced inhibitory controls, contribute to central sensitization and trigeminal nociceptor sensitization.

Conclusions:

• Disruption of central modulatory systems, particularly serotonin (5-HT) pathways, is implicated in MOH pathogenesis.
• Increased excitability of the trigeminal system and altered central pain modulation enhance pain perception.
• Chronic medication use may foster or reinforce medication overuse headache through these neurobiological alterations.