Aim: Somatostatin is a peptide hormone with predominantly inhibitory functions in many organ systems. Somatostatin analogs show antinociceptive effects and have been reported to be analgesic in severe pain syndromes and primary headaches. The involvement of somatostatin receptor types (sst1-5) in these effects is not yet clear. SOM230 is a somatostatin analogue with high binding affinity and functional activity at sst1, 2, 3 and 5 receptors. We examined if and at which dose SOM230 modulates neuronal activity in the rat spinal trigeminal nucleus of neurons with afferent input from the cranial dura mater as a model of meningeal nociception related to the generation of headaches. Methods: Single unit activity was recorded from neurons in the spinal trigeminal nucleus caudalis in artificially ventilated rats anaesthetised by isofluorane. Neurons were characterized according to their afferent input from facial areas and the parietal dura mater encephali exposed in a cranial window. Mechanical stimuli of short duration were repetitively applied to the receptive field in the exposed dura. Ongoing and mechanically evoked activity was observed under control conditions and after subcutaneous (s.c.) or intravenous (i.v.) applications of SOM230 at increasing doses. Results: SOM230 at s.c. doses of 3-30 mg/kg did not cause changes in neuronal activity within 30 min. The i.v. injection of SOM230 at doses of 3-100 mg/kg reduced ongoing and mechanically evoked neuronal activity in individual experiments without clear dose-dependency. The lowest dose after which a significant reduction in ongoing activity occurred in comparison to vehicle was 3 mg/kg in 3, 10 mg/kg in 4 and 100 mg/kg in 1 out of 8 experiments. Conclusion: SOM230 has weak inhibitory effects on the neuronal activity of central trigeminal neurons with meningeal afferent input. The site of action is unclear but may include central targets. Somatostatin sst1, 2, 3 and 5 receptors seem to be involved in the control of central trigeminal activity and may have a role in primary headaches.