Objective: Calcitonin gene-related peptide (CGRP) has been identified as a key mediator in meningeal nociception and the generation of headaches. Systemic but not local administration of the CGRP receptor antagonist olcegepant (BIBN4096BS) onto the rat dura mater decreased the activity of neurons in the spinal trigeminal nucleus (STN) with meningeal afferent input, while nitric oxide donors increased neuronal activity and sensitised trigeminal ganglion neurons for stimulated CGRP release. Since CGRP receptors have been localised on trigeminal ganglion neurons, we asked if inhibition of these receptors influences the activity of STN neurons. Methods: The skull of isofluorane anaesthetised rats was trepanised to expose the parietal dura mater and the medulla was made accessible. A 26 gauge needle connected to a catheter filled with fractions of 15 ml vehicle or olcegepant (10-3 M) was introduced through the infraorbital channel into the trigeminal ganglion. Carbon fibre glass electrodes were passed through the caudal STN to record activity from neurons with mechanical receptive fields in the exposed dura mater. In a separate group of experiments the nitric oxide donor glycerol trinitrate (GTN, 250 mg/kg) was slowly infused prior to the recordings. Results: Units showed spontaneous activity ranging from 10 to 500 min-1 and mechanically evoked activity of 8-40 s-1. In 8 animals not treated with GTN, neither vehicle nor olcegepant injection into the TG caused significant changes in activity within periods of 20-30 min. However, in 8 experiments with GTN pre-infusion olcegepant injection was followed by an increase in activity of STN neurons. Systemic parameters were not changed by the injections. Conclusion: In the naïve trigeminal ganglion CGRP receptors are not activated by CGRP, or their activation has no impact on the sensory transmission in the STN. Pre-treatment with nitric oxide may induce nociceptive but also antinociceptive effects in the trigeminal ganglion, which are mediated by CGRP autoreceptors and uncovered through their inhibition by olcegepant.