RESUMO
Cyclooxygenase-3 [Cox-3] is a recently identified cyclooxygenase which is inhibited by paracetamol related drugs rather than traditional non-steroidal anti-inflammatory. In this study the distribution of Cox-3 has been studied in the rat nervous system both in the central and peripheral nervous system. Ten adult male Wistar rats weighing 300-400 g were killed by decapitation under brief anesthesia. Nervous system; brains, spinal cords, spinal ganglia and spinal nerves were removed and processed for immunohistochemisty using an antibody raised against Cox-3. Cox-3 was widely distributed in the rat nervous system. The expression appeared mainly neuronal. In the central nervous system, Cox-3 was localized in neurons in the brain and spinal cord. In the brain Cox-3 was highly expressed in cerebral cortex, hippocampus and cerebellum. In the peripheral nervous system Cox-3 was localized in neurons in the spinal ganglia and in the spinal nerves. Cox-3 was widely distributed in the nervous system. Thus, this isoform could be contributing to the generation of the physiological levels of prostaglandins normally for needed for homeostatic regulation in the nervous system. Localisation of Cox-3 in areas associated with nociception and pain such as brain, spinal cord and spinal ganglia support the hypothesis that Cox-3 may be the central target of paracetamol and other related centrally acting analgesics/antipyretics
Assuntos
Animais de Laboratório , Sistema Nervoso , Ratos , Anti-Inflamatórios não EsteroidesRESUMO
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. 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]. 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. 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. 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