Platelet Serotonin in Patients with Analgesic-Induced Headache

Abstract

The purpose of this study was to investigate the role of serotonin (5HT) in patients with analgesic-induced headache (AIH). We estimated platelet 5HT concentration in patients with AIH, migraine patients and non-headache controls, by using high performance liquid chromatography with electrochemical detection. Our results revealed a significant decrease (p < 0.001) in platelet 5HT content in patients with AIH as compared to migraine patients and non-headache controls (221.8 +/- 30.7, 445.3 +/- 37.4 and 467.2 +/- 38.5 ng/10(9) platelets, respectively). In contrast, a difference of lesser statistical significance (p = 0.022) was observed in platelet 5HT content after incubation with excess 5HT (1940.0 +/- 195.1, 2610.0 +/- 173.1 and 2560 +/- 165.2 ng/10(9) platelets for patients with AIH, migraine patients and non-headache controls, respectively). These data suggest that analgesic-induced suppression of 5HT uptake may interfere with the function of the pain modulatory system in the brainstem. Although the process by which analgesics interfere with this system is as yet unknown, it is possible that it may not be entirely due to defective 5HT uptake mechanisms.

Pathophysiology of Medication-overuse Headache: Implications from Animal Studies

“…Tryptophan depletion increases nausea, headache, and photophobia in migraineurs [20]. Decreases in 5-HT levels also were reported in patients with MOH [21]. Animal experiments show that dysfunction of this transmitter system leads to several changes in the cerebral cortex and trigeminal system, which can increase the susceptibility of headache attacks.…”

Original article. Potential risk of dihydroergotamine causing medicationoveruse headache: preclinical evidence

“…A derangement of the central serotonin-dependent endogenous pain control system induced by chronic medication has been proposed [16]. Observation of a decrease in serotonin in patients with MOH supports this hypothesis [23].…”

Chronic daily headache: biochemical and neurotransmitter abnormalities

“…This activity may particularly be enhanced during druginduced headache, a mechanism similar to that occurring during opioid withdrawal. A decrease in platelet serotonin in migraine patients overusing analgesics has been demonstrated; this allows us to hypothesize that analgesic overuse depletes serotonin from storage sites, leading to an increase in the frequency of attacks [40,44].…”

“…A more recent study carried out by Srikiatkhachorn and Anthony [43] demonstrated a reduced content and uptake of 5-HT, as well as the upregulation of 5HT 2 receptors in platelets of patients with analgesic-induced headache. According to the authors, these findings suggested that analgesic-induced suppression of 5-HT uptake interferes with the function of the pain modulatory system in the brainstem [44].…”