Central sensitisation and activation of serotonin uptake in patients with medication overuse headache

Background: Central sensitization of pain processing may play pivotal role in the pathophysiology of medication overuse headache (MOH). One possible mechanism include alteration of the anti-nociceptive serotonergic neurons.

Objective: To investigate central pain processing and serotonin changes in MOH.

Methods: Healthy controls (n=18) and patients with episodic migraine (n=16), analgesic-induced headache (n=15) and triptan-induced headache (n=15) were studied both, before and after withdrawal. Patients with co-existing depression (BDI>21) were excluded. The nociceptive blink reflex (nBR) and pain related potentials (PRP) were recorded following stimulation of the forehead and hand. Kinetics of serotonin uptake in platelets was measured.

Results: In patients with MOH we found a facilitation of trigeminal nociceptive potentials (but not of blink reflex responses) and increase of serotonin uptake which normalized after withdrawal. There were no differences between patients overusing analgesics and those overusing triptans. Patients with episodic migraine did not differ from controls.

Conclusion: Augmentation of PRP but not of nBR indicates the leading role of supra-spinal nociceptive structures in processes of headache chronification. Increase of serotonin uptake in both analgesic and triptan induced MOH seems to be a consequence of a high headache frequency rather than a major underlying pathophysiological mechanism.