Riboflavin, which improves energy metabolism similarly to coenzyme Q10 (CoQ10), is effective in migraine prophylaxis. We compared CoQ10 (3 × 100 mg/day) and placebo in 42 migraine patients in a double-blind, randomized, placebo-controlled trial. CoQ10 was superior to placebo for attack-frequency, headache-days and days-with-nausea in the third treatment month and well tolerated; 50%-responder-rate for attack frequency was 14.4% for placebo and 47.6% for CoQ10 (number-needed-to-treat: 3). CoQ10 is efficacious and well tolerated.

The way in which medication overuse transforms episodic migraine into chronic daily headache is unknown. To search for candidate brain areas involved in this process, we measured glucose metabolism with 18-FDG PET in 16 chronic migraineurs with analgesic overuse before and 3 weeks after medication withdrawal and compared the data with those of a control population (n = 68). Before withdrawal, the bilateral thalamus, orbitofrontal cortex (OFC), anterior cingulate gyrus, insula/ventral striatum and right inferior parietal lobule were hypometabolic, while the cerebellar vermis was hypermetabolic. All dysmetabolic areas recovered to almost normal glucose uptake after withdrawal of analgesics, except the OFC where a further metabolic decrease was found. A subanalysis showed that most of the orbitofrontal hypometabolism was due to eight patients overusing combination analgesics and/or an ergotamine-caffeine preparation. Medication overuse headache is thus associated with reversible metabolic changes in pain processing structures like other chronic pain disorders, but also with persistent orbitofrontal hypofunction. The latter is known to occur in drug dependence and could predispose subgroups of migraineurs to recurrent analgesic overuse.

The phenomena of habituation and sensitization are considered most useful for studying the neuronal substrates of information processing in the CNS. Both were studied in primary headaches, that are functional disorders of the brain characterized by an abnormal responsivity to any kind of incoming innocuous or painful stimuli and it’s cycling pattern over time (interictal, pre-ictal, ictal). The present review summarizes available data on stimulus responsivity in primary headaches obtained with clinical neurophysiology. In migraine, the majority of electrophysiological studies between attacks have shown that, for a number of different sensory modalities, the brain is characterised by a lack of habituation of evoked responses to repeated stimuli. This abnormal processing of the incoming information reaches its maximum a few days before the beginning of an attack, and normalizes during the attack, at a time when sensitization may also manifest itself. An abnormal rhythmic activity between thalamus and cortex, namely thalamocortical dysrhythmia, may be the pathophysiological mechanism subtending abnormal information processing in migraine. In tension-type headache (TTH), only few signs of deficient habituation were observed only in subgroups of patients. By contrast, using grand-average responses indirect evidence for sensitization has been found in chronic TTH with increased nociceptive specific reflexes and evoked potentials. Generalized increased sensitivity to pain (lower thresholds and increased pain rating) and a dysfunction in supraspinal descending pain control systems may contribute to the development and/or maintenance of central sensitization in chronic TTH. Cluster headache patients are chrarcterized during the bout and on the headache side by a pronounced lack of habituation of the brainstem blink reflex and a general sensitization of pain processing. A better insight into the nature of these ictal/interictal electrophysiological dysfunctions in primary headaches paves the way for novel therapeutic targets and may allow a better understanding of the mode of action of available therapies.