Plasticity of 5-HT serotonin receptor in patients with analgesic-induced transformed migraine.
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 5-HT2A 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 (Bmax) 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 (Kd) 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 nonheadache controls, respectively). A significant decrease in Bmax 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 Kd value was observed (1.95 +/- 0.12 and 2.47 +/- 0.30 nmol, respectively). These findings indicate that 5-HT2A 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.
Srikiatkhachorn
A
A
Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Puangniyom
S
S
Govitrapong
P
P
D000328:Adult; D000700:Analgesics / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000139:chemically induced* / Q000503:physiopathology; D009473:Neuronal Plasticity; D011985:Receptors, Serotonin / Q000502:physiology*
D000700:Analgesics; D011985:Receptors, Serotonin