Zolmitriptan Reduces the Size of the Neurogenic Flare Reaction and the Primary Hyperalgesia after Electrical Stimulation

The triptan's mode of action (migraine medication) is not fully understood. Experimental data suggest a peripheral and a central pathomechanism. The aim of this study was the evaluation of zolmitriptan's (Z) impact on the peripheral neuropeptide release (neurogenic flare) and the primary and secondary hyperalgesia after electrical stimulation. Moreover, systematic differences between migraine patients and controls were examined. The study was performed in a double-blind, placebo-controlled and cross-over design. Ten migraine patients (8 female, 2 male; age 26.4±1.4 years) and 10 healthy controls (5 female, 5 male; 24.8±0.8 years) were included. Each participant underwent 2 sessions: one 90 minutes after oral administration of Z and the other 90 minutes after placebo exposure. Four microdialysis fibers equipped with stainless steel for electrical stimulation were inserted into the right ventral thighs and perfused with NaCl. Electrical current was delivered via a constant-current generator (Digitimer) and stepwise increased to 20mA. Electrically-induced pain was rated on a visual analogue scale (VAS) every minute. The electrically-induced axon-reflex flare was measured by a laser Doppler imager. The analysis of the heat pain threshold (TSA 2001) and the mechanical hyperalgesia for pinprick stimuli (Pinprick, intensity 8–512 mN) and dynamic mechanical allodynia (Q-tip, cotton wisp, brush) were assessed directly before and after electrical exposure. For statistical analysis an ANCOVA was calculated. Neurogenic flare: Z downsized the area of the neurogenic flare significantly (p<0.002). No influence on the intensity of the flare (laser Doppler flux) could be observed (ns). The pain rating on the VAS was significantly reduced after Z administration (p<0.04). QST: After electrical stimulation a significant heat- and pinprick hyperalgesia was found in the area of primary hyperalgesia (p<0.05). The hyperalgesia to pinprick but not to heat was significantly decreased by Z (p<0.05). QST parameters in the area of secondary hyperalgesia were unaffected by Z (ns). Our results indicate that Z 1) reduces the excitability of primary afferents resulting in a downsizing of the neurogenic flare and 2) induces a reduction of primary hyperalgesia in our pain-model. The secondary hyperalgesia which is normally interpreted as a sensitization of central neuroceptive neurons was unaffected. These data suggest that Z inhibits the release of neuropeptides and the sensitization of primary afferents.