Paired nociceptive blink stimuli can facilitate trigeminofacial circuit at a long inter-stimulus interval

Backgrounds: Conditioned responses of paired nociceptive blink reflex (nBR) can reflect the excitability of trigeminofacial circuit. In the present study, we studied paired homotopic nBR with different inter-stimulus intervals (ISI). By monitoring different ISIs and consequential conditioned R2 of nBR, we aimed to investigate the impact of ISIs on the recovery cycle of nBR in normal individuals. Methods: Twelve healthy volunteers (mean age: 29.9 ± 7.0 years; M/F: 7/5) were enrolled in this study. After individuals' reflex threshold was determined, triple pulses were given in pairs with ISIs 125 to 10000 milliseconds randomly. We calculated the ratio of conditioned and unconditioned nBR area-under-curve (AUC) (defined as recovery index), and amplitude of each ISI. Results: The average latency of unconditioned nR2 is 42.6 ± 5.5 ms, with amplitude of 53.4 ± 43.9 μV and the AUC of 563.5 ± 480.6 ms∙μV. The conditioned nBR/unconditioned nBR response ratio was less than 100% while the ISI is shorter than 1667 ms, suggesting an inhibited conditioned response. The recovery index and the amplitude of conditioned nBR gradually increased with increasing ISI. The recovery index was greater than 100% at ISI of 10 s (p = 0.005), implying full recovery and facilitation of conditioned nBR. Conclusion: Our study established the time-dependent dynamic recovery curve of paired nBR. The facilitated nBR at ISI longer than 10 s might be associated with temporal summation to the facial motor neurons after repeated stimuli. Our study results provided potential applications for patients with pain disorders involving trigeminofacial region.