Orbitofrontal cortex involvement in chronic analgesic-overuse headache evolving from episodic migraine

Abstract

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.

Psychiatric screening for migraine patients

“…The partial benefit from detoxification and the severity bias led us to consider this subgroup of chronic-relapsing migraneurs as a separate phenotype, whose features might belong to the substance use disorders spectrum. Recent findings from neuroimaging and neuropsychological studies give strength to this hypothesis [6][7][8]30]. However, this study has a number of limitations.…”

“…The underlying neurobiology of MO is not well understood. Although it might come from coping with pain and disability associated with migraine, a persistent dysfunction of the orbitofrontal cortex (OFC) and the relative decision-making deficit have been recently reported [6][7][8]. These deficits might explain the above-mentioned maladaptive behaviors and place MO in the substance use disorders spectrum [6].…”

Diagnosis, pathophysiology and management of chronic migraine: a proposal of the Belgian Headache Society

“…central pain modulation [133,134] no % of posterior circulation infarcts [104] Medication overuse headache ! metabolism and tissue density orbitofrontal cortex [48,50] ! metabolism/activation of lateral pain system [50,135] %% cortical sensitivity depending on drug overused [49] precuneus connectivity: !…”

“…metabolism and tissue density orbitofrontal cortex [48,50] ! metabolism/activation of lateral pain system [50,135] %% cortical sensitivity depending on drug overused [49] precuneus connectivity: ! with DMN, % with hippocampus [51] % tissue density in PAG [48] Acta Neurol Belg…”

Understanding the relationship between pain and emotion in idiopathic headaches

“…Furthermore, a PET study [17] has shown orbitofrontal cortex hypometabolism both in patients with chronic analgesic-overuse headache evolving from episodic migraine, and in patients with drug dependence. Similarly, an fMRI study carried out by our group [18] showed that female patients with chronic migraine with medication overuse (CMwMO) had hypoactivity, compared to controls, in some areas of the lateral pain pathway, primary somatosensory cortex (S1) and posterior parietal cortex (PPC), following noxious mechanical stimuli.…”