Plasticity of 5-HT(2A) serotonin receptor in patients with analgesic- induced transformed migraine

Abstract

Chronic drug exposure can induce a significant change in neurotransmitter receptor systems and is possibly involved in the pathogenesis of drug-induced neurological disorders. Abuse of analgesics is known to induce deterioration in headache status in patients with primary headaches, especially migraine. To assess the possibility of 5HT(2A) serotonin receptor plasticity in this condition, we investigated receptor binding on the platelet membrane in patients with analgesic-induced transformed migraine, patients with migraine, and nonheadache controls. Various concentrations of [3H]-spiperone (0.4 to 12 nmol) was used as a radioligand, and ketanserin was used to determine nonspecific binding. A lower maximal number of receptors (B(max)) was observed in patients with migraine as compared to patients with transformed migraine, and controls (467 ± 58, 708 ± 36, and 786 ± 64 fmol/mg protein, respectively, P<0.01); whereas the value of the dissociation equilibrium constant (K(d)) remained unchanged (1.72 ± 0.16, 1.41 ± 0.13 and 1.25 ± 0.21 nmol for patients with migraine, patients with transformed migraine, and non- headache controls, respectively). A significant decrease in B(max) value was observed in patients with transformed migraine after 4 weeks of analgesic withdrawal (770 ± 25 and 345 ± 31 fmol/mg protein P<0.001), whilst no significant change in K(d) value was observed (1.95 ± 0.12 and 2.47 ± 0.30 nmol, respectively). These findings indicate that 5-HT(2A) serotonin receptor system is altered in patients with transformed migraine with analgesic overuse. Such receptor plasticity may be an important step in the pathogenic mechanism of transformed migraine.