Article

Increased activity of serotonin uptake in platelets in medication overuse headache following regular intake of analgesics and triptans

Department of Neurology, University of Duisburg-Essen, Hufelandstr. 55, Essen 45122, Germany.
The Journal of Headache and Pain (Impact Factor: 2.8). 05/2008; 9(2):109-12. DOI: 10.1007/s10194-008-0019-9
Source: PubMed

ABSTRACT

We investigated the effect of chronic administration of different pain medications on the activity of the serotonin transporter (SERT) in patients with medication overuse headache (MOH). We measured the kinetic of platelet 5-HT uptake (maximal velocity, Vmax and the Michaelis-Menten constant, Km in patients with overuse of triptans (tMOH, n = 15) or analgesics (aMOH, n = 14) before and after drug withdrawal, as well as in headache-free healthy subjects (n = 15) and patients with episodic migraine (EM, n = 16). Vmax was increased similarly in both, tMOH and aMOH compared to healthy subjects and patients with EM and normalized after withdrawal in parallel to the improvement of headache frequency. Average Km was similar in all groups at baseline and not affected by the withdrawal. The data demonstrate a transient increase of SERT activity in patients with analgesic and triptan induced MOH but do not allow to differentiate whether the increase of serotonin uptake is caused by regular intake of analgesics or triptans or is a consequence of frequent headache attacks.

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    • "By contrast, in rats chronically treated with analgesics, 5-HT2A receptors are down-regulated [34] and the 5-HT transporter is up-regulated in the cortex [34] and in platelets [35]. Upregulated platelet 5-HT transporters [35] and decreased whole blood 5-HT levels [36] tend to normalize after drug withdrawal. Collectively, these experimental data suggest that anti-migraine drug overuse can disrupt central 5-HT transmission. "
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    ABSTRACT: Medication-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. We 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. In 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. 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.
    Full-text · Article · Dec 2010 · BMC Neurology
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    • "Mal de cap: Abús farmacològic 70 postula la possibilitat que es produeixi una adaptació cel·lular a nivell cerebral o canvis en la substancia gris periaqueductal (Cupini i Calabresi, 2005). En relació a la serotonina, el grup de Ayzenberg et al., (2008) han estudiat l'activitat dels transportadors de serotonina en pacients amb mal de cap i abús a triptans, abús a analgèsics, en pacients amb migranya episòdica i en un grup de controls sans sense mal de cap. Han analitzat la cinètica de la resposta serotoninèrgica, abans i després de la retirada de medicació, i han observat un augment de la velocitat màxima dels transportadors en els dos grups de pacients, que feien abús, en comparació al grup de migranya episòdica i controls que es normalitzava després de la retirada de medicació. "
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