title: Glutamate-mediated astrocyte-to-neuron signalling in the rat dorsal horn.
abstract: By releasing neuroactive agents, including proinflammatory cytokines, prostaglandins and neurotrophins, microglia and astrocytes are proposed to be involved in nociceptive transmission, especially in conditions of persistent, pathological pain. The specific action on dorsal horn neurons of agents released from astrocytes, such as glutamate, has been, however, poorly investigated. By using patch-clamp and confocal microscope calcium imaging techniques in rat spinal cord slices, we monitored the activity of dorsal horn lamina II neurons following astrocyte activation. Results obtained revealed that stimuli that triggered Ca(2+) elevations in astrocytes, such as the purinergic receptor agonist BzATP and low extracellular Ca(2+), induce in lamina II neurons slow inward currents (SICs). Similarly to SICs triggered by astrocytic glutamate in neurons from other central nervous system regions, these currents (i) are insensitive to tetrodotoxin (TTX), (ii) are blocked by the NMDA receptor (NMDAR) antagonist d-AP5, (iii) lack an AMPA component, and (iv) have slow rise and decay times. Ca(2+) imaging also revealed that astrocytic glutamate evokes NMDAR-mediated episodes of synchronous activity in groups of substantia gelatinosa neurons. Importantly, in a model of peripheral inflammation, the development of thermal hyperalgesia and mechanical allodynia was accompanied by a significant increase of spontaneous SICs in dorsal horn neurons. The NMDAR-mediated astrocyte-to-neuron signalling thus represents a novel pathway that may contribute to the control of central sensitization in pathological pain.
authors.affiliation: Department of Biomedical Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41100 Modena, Italy. bardoni@unimo.it
authors.forename: Rita
authors.initials: R
authors.lastname: Bardoni
authors.forename: Alessia
authors.initials: A
authors.lastname: Ghirri
authors.forename: Micaela
authors.initials: M
authors.lastname: Zonta
authors.forename: Chiara
authors.initials: C
authors.lastname: Betelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitale
authors.forename: Valentina
authors.initials: V
authors.lastname: Ruggieri
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sandrini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Carmignoto
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D020671:Posterior Horn Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents; D018698:Glutamic Acid