Immunohistochemical Localization of Paracetamol Sensitive Cyclooxygenase (Cox-3) in Rat Trigemino-Vascular System: A possible Role in the Mechanism of Migraine/Headache Pain

Introduction: Prostaglandins are synthesized by the activity of cyclooxygenase (Cox) isoforms. The newly discovered isoform (Cox-3) has been shown to be potently inhibited by centrally-acting analgesics, such as acetaminophen (paracetamol) which are widely used in treatment of headache. Vascular headaches such as migraine are hypothesized to be due to neural activation in the trigemino-vascular system. This results in vasodilatation of meningeal blood vessels leading to activation of trigeminal sensory afferents and pain. Headache is thus attributable to a neurovascular interaction. Aim of the Work: In this study the localisation of Cox-3 has been studied in structures known to be involved in pathogenesis of headache including rat dura mater and trigeminal pathway (trigemino-vascular system). Materials and Methods: Fifteen adult male Wistar rats weighing 300-400g were killed by decapitation under brief anaesthesia. The dura mater, the trigeminal ganglia and brain were removed and processed for immunohistochemistry using an antibody raised against Cox-3. Results: Dura mater showed Cox-3 immunoreactivity in meningeal blood vessels, perivascular nerve fibres and mast cells. In the trigeminal ganglia, Cox-3 immunoreactivity was localised in neurons of different sizes and in trigeminal nerve fibres. In the brain stem, Cox-3 was localised in neurons in the trigeminal nuclei. Conclusion: These data provide evidence that Cox-3 is expressed in both neuronal and vascular structures known to be involved in pathogenesis of vascular headache. These data support the hypothesis that Cox-3 may be a central target of paracetamol and related analgesics.