Serotonin receptor adaptation in patients with analgesic-induced headache

Analgesic abuse has recently been recognized as a cause of deterioration in primary headache patients. Although the pathogenesis of this headache transformation is still obscure, alteration of serotonin receptor function is one possible mechanism. To assess the plasticity of 5HT₂ serotonin receptors in this condition, we investigated receptor binding by the platelet membrane in patients with analgesic-induced headache (AIH), migraine and non-headache controls. The technique involved radioligand binding with (phenyl-4-³H)spiperone and ketanserin. A greater density of receptor numbers (B_max) was found in patients with AIH and in non-headache controls (96.47±10.2 and 92.01±13.15 fmol/mg protein), as compared to migraine patients (49.52±5.14 fmol/mg protein). The value of dissociation equilibrium constant (K_D) remained unchanged (3.07±0.49, 2.24±0.24 and 2.9±0.42 nM for patients with AIH, migraine and non-headache controls, respectively). Based on these findings, we suggest that up-regulation of 5HT₂ serotonin receptors may be a possible mechanism of headache transformation in patients with AIH.