Orbitofrontal cortex hypometabolism, medication overuse headache, substance abuse and migraine: key pathophysiological issues

Sir, Professor Schoenen and colleagues show reversible metabolic changes in pain processing structures along with persistent orbitofrontal cortex (OFC) hypofunction in patients with medication overuse headache (MOH); these investigators extrapolate these positron emission tomography (PET) findings to both analgesic drug-dependence as well as to the pathogenesis of MOH itself (Fumal et al ., 2005). At the outset, the basic research premise of a causal relation between medication overuse and aggravation or transformation of primary headache disorders is uncertain and likely linked to headache frequency (Tepper and Dodick, 2002; Lipton and Bigal, 2003). The present paper (Fumal et al ., 2005) does not emphasize that: (i) Few migraine patients regularly using analgesics develop chronic daily headache (CDH) or MOH or chronic migraine. This issue needs to be distinguished from the incidence of acute medication overuse in a substantial fraction of patients with chronic headaches seen in prospective studies in specialized headache centres or the general population (Zwart et al ., 2003; Katsarava et al ., 2004). The key pathophysiological concern in MOH is not the incidence of acute medication overuse but its role in transformation of episodic migrainous headache to a more frequent/daily occurrence. Epidemiological evidence is quite unlikely to settle the cause–effect relationship between acute medication overuse and MOH or chronic migraine. (ii) While analgesic abuse is a self-determined unsupervised activity, analgesic withdrawal is a medically controlled activity—supervised analgesic withdrawal involves the placebo effect of the therapist's reassurance. Every therapeutic intervention—including supervised analgesic withdrawal—involves a placebo effect (Bignall, 1994). (iii) Analgesic withdrawal in clinical practice is commonly accompanied by other interventions undertaken simultaneously (Lipton and Bigal, 2003). (iv) No particular temporal pattern has emerged between regular analgesic use and development of daily headache in migraine …