Plasticity of 5-HT2A serotonin receptor in patients with analgesic-inducedtransformed migraine

Chronic drug exposure can induce a significant change in neurotransmitter r eceptor systems and is possibly involved in the pathogenesis of drug-induce d neurological disorders; Abuse of analgesics is known to induce deteriorat ion in headache status in patients with primary headaches, especially migra ine. To assess the possibility of 5-HT2A serotonin receptor plasticity in t his condition, we investigated receptor binding on the platelet membrane in patients with analgesic-induced transformed migraine, patients with migrai ne, and nonheadache controls. Various concentrations of [H-3]-spiperone (0. 4 to 12 nmol) was used as a radioligand, and ketanserin was used to determi ne nonspecific binding. A lower maximal number of receptors (B-max) was obs erved in patients with migraine as compared to patients with transformed mi graine, and controls (467 +/- 58, 708 +/- 36, and 786 +/- 64 fmol/mg protei n, 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 migrain e, and nonheadache 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,vas observed (1.95 +/- 0.12 and 2 .47 +/- 0.30 nmol, respectively). These findings indicate that 5-HT2A serot onin 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.