PURINERGIC TRANSMISSION IN MIGRAINE: ROLE OF P2Y RECEPTORS IN THE SPINAL-TRIGEMINAL SYSTEM IN VIVO AND IN VITRO
type: CreativeWork
description: Migraine is a highly disabling neurovascular disorder, affecting about 15% of adults in the Western World, with considerable socio-economic implications on both productivity and quality of life (Goadsby, 2007). Despite the progresses made in migraine research during the past few decades, there is little or no evidence that shows with certainty which and how pain fibers are activated during migraine attacks. Most investigators currently believe that a migraine attack starts in the brain, as suggested by premonitory symptoms. However, a debate about migraine origin is still ongoing: some scientists argue for a central origin of the headache pain (Goadsby et al., 2009), whereas others, including our research group, believe that the headache is triggered by activation of peripheral nociceptors. Indeed, the trigeminal nerve conveys sensory information from most extracranial and intracranial structures to the spinal trigeminal nucleus, and it has been therefore hypothesized that migraine could arise from a primary dysfunction leading to activation and sensitization of the trigemino-vascular system (Olesen et al., 2009). On this basis, the final aim of my study have been setting up both in vitro and in vivo models, as tools for evaluating the molecular and cellular role of the purinergic system in trigeminal pain transmission, in order to identify new potential targets for migraine pain therapy. In the first part of my PhD experimental work we have characterized the presence, functionality, and cellular localization of P2 receptors in primary mixed neuron-glia cultures prepared from mouse TG. Our results show that TG sensory neurons mainly express functional P2X3 receptors, while SGCs are highly responsive to P2Y-agonists (i.e., ADP, UTP, and UDP). Moreover, exposure to the pro-inflammatory agent BK significantly modified P2X3 receptor function in a biphasic way, with an upregulation or a reduction of alpha,beta-meATP-mediated calcium responses after an acute or chronic ex…
abstract: Migraine is a highly disabling neurovascular disorder, affecting about 15% of adults in the Western World, with considerable socio-economic implications on both productivity and quality of life (Goadsby, 2007). Despite the progresses made in migraine research during the past few decades, there is little or no evidence that shows with certainty which and how pain fibers are activated during migraine attacks. Most investigators currently believe that a migraine attack starts in the brain, as suggested by premonitory symptoms. However, a debate about migraine origin is still ongoing: some scientists argue for a central origin of the headache pain (Goadsby et al., 2009), whereas others, including our research group, believe that the headache is triggered by activation of peripheral nociceptors. Indeed, the trigeminal nerve conveys sensory information from most extracranial and intracranial structures to the spinal trigeminal nucleus, and it has been therefore hypothesized that migraine could arise from a primary dysfunction leading to activation and sensitization of the trigemino-vascular system (Olesen et al., 2009). On this basis, the final aim of my study have been setting up both in vitro and in vivo models, as tools for evaluating the molecular and cellular role of the purinergic system in trigeminal pain transmission, in order to identify new potential targets for migraine pain therapy. In the first part of my PhD experimental work we have characterized the presence, functionality, and cellular localization of P2 receptors in primary mixed neuron-glia cultures prepared from mouse TG. Our results show that TG sensory neurons mainly express functional P2X3 receptors, while SGCs are highly responsive to P2Y-agonists (i.e., ADP, UTP, and UDP). Moreover, exposure to the pro-inflammatory agent BK significantly modified P2X3 receptor function in a biphasic way, with an upregulation or a reduction of alpha,beta-meATP-mediated calcium responses after an acute or chronic ex…
author: G. Villa
language: eng
keywords: MIGRAINE, ATP, GLIAL CELLS, TRIGEMINAL GANGLIA, PAIN, P2Y RECEPTORS, Settore BIO/14 - Farmacologia
date published: 2010-12-15
date modified: 2026-07-27T20:19:17Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2434/150195

PropertyValue
property ID: DOI
value: 10.13130/villa-giovanni_phd2010-12-15