title: Central sensitization of nociceptive neurons in rat medullary dorsal horn involves purinergic P2X7 receptors.
abstract: Central sensitization is a crucial process underlying the increased neuronal excitability of nociceptive pathways following peripheral tissue injury and inflammation. Our previous findings have suggested that extracellular adenosine 5'-triphosphate (ATP) molecules acting at purinergic receptors located on presynaptic terminals (e.g., P2X2/3, P2X3 subunits) and glial cells are involved in the glutamatergic-dependent central sensitization induced in medullary dorsal horn (MDH) nociceptive neurons by application to the tooth pulp of the inflammatory irritant mustard oil (MO). Since growing evidence indicates that activation of P2X7 receptors located on glia is involved in chronic inflammatory and neuropathic pain, the aim of the present study was to test in vivo for P2X7 receptor involvement in this acute inflammatory pain model. Experiments were carried out in anesthetized Sprague-Dawley male rats. Single unit recordings were made in MDH functionally identified nociceptive neurons for which mechanoreceptive field, mechanical activation threshold and responses to noxious stimuli were tested. We found that continuous intrathecal (i.t.) superfusion over MDH of the potent P2X7 receptor antagonists brilliant blue G and periodated oxidized ATP could each significantly attenuate the MO-induced MDH central sensitization. MDH central sensitization could also be produced by i.t. superfusion of ATP and even more effectively by the P2X7 receptor agonist benzoylbenzoyl ATP. Superfusion of the microglial blocker minocycline abolished the MO-induced MDH central sensitization, consistent with reports that dorsal horn P2X7 receptors are mostly expressed on microglia. In control experiments, superfusion over MDH of vehicle did not produce any significant changes. These novel findings suggest that activation of P2X7 receptors in vivo may be involved in the development of central sensitization in an acute inflammatory pain model.
authors.affiliation: Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, ON, Canada M5G 1G6.
authors.forename: K
authors.initials: K
authors.lastname: Itoh
authors.forename: C-Y
authors.initials: CY
authors.lastname: Chiang
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: J-C
authors.initials: JC
authors.lastname: Lee
authors.forename: J O
authors.initials: JO
authors.lastname: Dostrovsky
authors.forename: B J
authors.initials: BJ
authors.lastname: Sessle
mesh_terms: D000818:Animals; D059333:Central Nervous System Sensitization / Q000502:physiology*; D003782:Dental Pulp / Q000294:innervation; D004594:Electrophysiology; D008297:Male; D017628:Microglia / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D014275:Trigeminal Caudal Nucleus / Q000378:metabolism*
chemical_list: D058486:Receptors, Purinergic P2X7