Abnormal cortical responses to somatosensory stimulation in medication-overuse headache

Abstract

BackgroundMedication-overuse headache (MOH) is a frequent, disabling disorder. Despite a controversial pathophysiology convincing evidence attributes a pivotal role to central sensitization. Most patients with MOH initially have episodic migraine without aura (MOA) characterized interictally by an absent amplitude decrease in cortical evoked potentials to repetitive stimuli (habituation deficit), despite a normal initial amplitude (lack of sensitization). Whether central sensitization alters this electrophysiological profile is unknown. We therefore sought differences in somatosensory evoked potential (SEP) sensitization and habituation in patients with MOH and episodic MOA.MethodsWe recorded median-nerve SEPs (3 blocks of 100 sweeps) in 29 patients with MOH, 64 with MOA and 42 controls. Episodic migraineurs were studied during and between attacks. We measured N20-P25 amplitudes from 3 blocks of 100 sweeps, and assessed sensitization from block 1 amplitude, and habituation from amplitude changes between the 3 sequential blocks.ResultsIn episodic migraineurs, interictal SEP amplitudes were normal in block 1, but thereafter failed to habituate. Ictal SEP amplitudes increased in block 1, then habituated normally. Patients with MOH had larger-amplitude block 1 SEPs than controls, and also lacked SEP habituation. SEP amplitudes were smaller in triptan overusers than in patients overusing nonsteroidal anti-inflammatory drugs (NSAIDs) or both medications combined, lowest in patients with the longest migraine history, and highest in those with the longest-lasting headache chronification.Conclusions In patients with MOH, especially those overusing NSAIDs, the somatosensory cortex becomes increasingly sensitized. Sensory sensitization might add to the behavioral sensitization that favors compulsive drug intake, and may reflect drug-induced changes in central serotoninergic transmission.

Altered processing of sensory stimuli in patients with migraine

“…Deficient habitu ation was also subsequently described for several other modality specific evoked potentials: pattern reversal visual evoked potentials (VEPs), [33][34][35][36][37][38][39][40][41][42] visual evoked magneto encephalographic (MEG) responses, 43 auditory evoked potentials (AEPs), 51,52 and somatosensory evoked poten tials (SSEPs). [53][54][55] Several other studies, however, were not able to reproduce these results and found no habitu ation deficit in individuals with migraine, possibly because of differences in the methods used or selection of patients. [56][57][58][59][60][61][62] The reasons for the discrepant results of habituation studies are not fully understood.…”

“…In triptan over users, the initial SSEP amplitude is normal, whereas it is increased in overusers of NSAIDs and in those overusing drugs from both classes. 54,85 In both groups of overusers, however, SSEP habituation was abnormal.…”

“…Interestingly, the habituation deficit reappears when patients evolve from chronic to episodic migraine. 83 Since the response pattern in chronic migraine is indistinguishable from that observed during migraine attacks, 43,[51][52][53][54][55][56][57][58][59][60][61][62][70][71][72] our research group has suggested that patients with chronic migraine are locked in an ictal like state. 84 The most prevalent factor associated with the tran sition from episodic to chronic migraine is acute medication overuse.…”

“…In medication overuse headache (MOH), the cortical response pattern suggests that the brain is locked in a preictal state, characterized by an increased amplitude of responses to intermittent stimuli (sensitization) and a consistent deficit of habituation to continuous or repetitive stimuli. 54 This pattern might vary with the class of drug overused. In triptan over users, the initial SSEP amplitude is normal, whereas it is increased in overusers of NSAIDs and in those overusing drugs from both classes.…”

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

“…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…”