Pathophysiology and management of transformed migraine and medication overuse headache.

There is considerable overlap in the mechanisms mediating migraine headache pain and sustained opioid-induced paradoxical pain. Both involve upregulation of calcitonin gene-related peptide and increased excitability of dorsal horn neurons. Descending facilitation from the rostral ventromedial medulla may contribute to this increased excitability. Using special magnetic resonance imaging techniques, high iron levels were found in the periaqueductal gray of patients with chronic daily headache with medication overuse. The periaqueductal gray is the center of a powerful descending antinociceptive neuronal network and projects to the rostral ventromedial medulla and subsequently to the dorsal horn. The periaqueductal gray is also involved in the behavioral response to opiate withdrawal. Dysfunction in the periaqueductal gray may explain why frequent analgesic use can result in medication overuse headache in migraineurs. Management of transformed migraine with medication overuse involves patient education, biobehavioral therapy, withdrawal of overused acute medications, bridge therapy for withdrawal headache, initiation of preventive medication, and close follow-up.