CELLULAR ADAPTATION IN MIGRAINEURS WITH CHRONIC DAILY HEADACHE

Ergotamine and analgesic misuse are now recognized as causes of chroni c daily headache and the condition responds well to drug withdrawal wi th reduced headache frequency. In this study, we have investigated whe ther medication misuse is associated with an alteration in membrane tr ansduction which is sensitive to drug withdrawal. This was carried out by assay of the thrombin-stimulated generation of inositol phosphates in platelets from 12 migraine patients with chronic daily headache an d analgesic misuse, 7 migraine patients with chronic daily headache an d ergotamine misuse and 7 control subjects. After drug withdrawal, a s ignificant decrease in headache frequency was seen at one month in bot h patient groups. Withdrawal of analgesics produced a significant decr ease in thrombin-stimulated inositol phosphate production at one month ; this was further decreased a month later with a reduction in B(max) of 60% and no significant change in K(D). A similar pattern was obtain ed in ergot misuse patients, with the K(D) value decreasing by 56% one month after drug withdrawal. These results provide evidence of an ada ptation in transduction with misuse of analgesics and ergotamine which correlates with headache frequency.