A Neuronal Hyper-responsiveness in PRVEPs of Migraine Patients

BACKGROUND: Although a number of visual evoked potentials (VEPs) studies have been performed to elucidate the pathophysiology of migraines, their results have been controversial. We studied the pattern-reversal visual evoked potentials (PRVEPs) during long periods of stimulation to show whether or not PRVEPs in migraines are abnormal. METHODS: Patients were divided into two groups; Group 1 (migraine with aura; MWA, n=29) and Group 2 (migraine without aura ; MOA, n=32) according to the International Headache Society criteria. PRVEPs were performed in both groups and in healthy volunteers (n=62). PRVEPs were averaged in 100 responses for a total duration of 10 minutes after an initial 3 minutes during stimulation and were analysed in terms of latencies and peak to peak amplitudes of N1-P1 and P1-N2 peaks. RESULTS: Amplitudes of PRVEPs in migraines showed significant increases compared to normal subjects (p<0.001), and amplitudes of PRVEPs in MWA showed significant increases compared to those in MOA (p<0.05). CONCLUSIONS: These results are explained by cortical hypoexcitability and hyper-responsiveness in migraine and by additional cortical hyper-responsiveness (another hyper-responsiveness) in MWA compared to MOA. We suggest that serotonergic and noradrenergic hyperactivity could be responsible for cortical hypoexcitability and hyper-responsiveness in a migraine brain. Another hyper-responsiveness in MWA could also be thought of as some evidence for cortical neuronal abnormality in MWA in addition to serotonergic and noradrenergic hyperactivity in a migraine brain. (J Korean Neurol Assoc 19(3):239~244, 2001)

Effects of Fluoxetine on Sodium Currents in Rat Sensory Neurons

BACKGROUND: Fluoxetine, a widely used antidepressant drug, has been described as a selective serotonin reuptake inhibitor. In addition to its antidepressant action it has been demonstrated to be effective in alleviating pain associated with various diseases. Dorsal root ganglion (DRG) neurons are primary sensory neurons and transmit peripheral information to central nervous system. Two types of sodium channels are expressed in DRG neurons based on their sensitivity to tetrodotoxin. They are involved in the generation and conduction of nociception. The effects of fluoxetine on sodium currents in DRG neurons were examined to elucidate the analgesic mechanism of the drug. METHODS: DRG neurons wereacutely dissociated from rats (2~6 days postnatal) by enzymatic digestion. The whole-cell configuration of patch clamp technique was used to record tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium currents. RESULTS: Fluoxetine inhibited TTX-S and TTX-R sodium currents with Kd values of 60 microM and 59 microM, respectively, at the holding potential of -80 mV. For both types of sodium channels the steady-state inactivation curves were shifted in the hyperpolarizing direction and the conductance-voltage relationship curves were shifted in the depolarizing direction by fluoxetine. These effects combined together would greatly reduce the neuronal excitability. CONCLUSIONS: The blockade of sodium currents in sensory neurons is considered as a possible mechanism for the analgesic action of fluoxetine.