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Results A total of 30 neurons in the TCC responsive to nociceptive activation of the dura mater were studied. A sub-poplation, 9 out of the 30, showed an average inhibition of firing of 65±14% from baseline with CSD. This inhibitory response was reversed by intravenous administration of the 5-HT1B/1D receptor antagonist, GR127935 (3mg/kg), and a mu-opioid antagonist, naloxone (1.5 mg/kg), five minutes after injection (p < 0.05). Conclusion The present findings show that repetitive CSDs inhibit a subpopulation of dural nociceptive trigeminal neurons, an effect mediated by serotonin and opioids receptors. Understanding how the cerebral cortex modulates trigeminovascular nociception will improve our understanding of the pathophysiology of migraine.

KCl-induced repetitive cortical spreading depression inhibits trigeminal neuronal firing mediated by 5-HT1B/1D and opioid receptor