Neurophysiological markers of central sensitisation in the trigeminal pathway and their modulation by the cyclo-oxygenase inhibitor ketorolac
Central sensitisation is a key mechanism of migraine; understanding its modulation by anti-migraine drugs is essential for rationalising treatment. We used an animal model of central trigeminal sensitisation to investigate neuronal responses to dural electrical stimulation as a putative electrophysiological marker of sensitisation and its modulation by ketorolac. In anaesthetised rats, responses of single convergent wide-dynamic range neurons of the spinal trigeminal nucleus to dural electrical simulation were recorded in parallel to their ongoing activity and responses to facial mechanical stimulation before and after a short-term dural application of an IS. Both ongoing activity and responses to dural electrical stimuli were enhanced by the inflammatory challenge, whereas neuronal thresholds to mechanical skin stimulation were reduced ( p < .05, N = 12). Intravenous ketorolac (2 mg/kg, N = 6) reduced ongoing activity and responses to dural electrical stimulation, and increased mechanical thresholds versus vehicle controls ( p < .05, N = 6). We conclude that neuronal responses to dural electrical stimulation can serve as a suitable marker which together with admitted electrophysiological signs can objectively detect central trigeminal sensitisation and its modulation by anti-migraine treatments in this preclinical model of migraine.