title: Endogenous ATP involvement in mustard-oil-induced central sensitization in trigeminal subnucleus caudalis (medullary dorsal horn).
abstract: Central sensitization represents a sustained hypersensitive state of dorsal horn nociceptive neurons that can be evoked by peripheral inflammation or injury to nerves and tissues. It reflects neuroplastic changes such as increases in neuronal spontaneous activity, receptive field size, and responses to suprathreshold stimuli and a decrease in activation threshold. We recently demonstrated that purinergic receptor mechanisms in trigeminal subnucleus caudalis (Vc; medullary dorsal horn) are also involved in the initiation and maintenance of central sensitization in brain stem nociceptive neurons of trigeminal subnucleus oralis. The aim of the present study was to investigate whether endogenous ATP is involved in the development of central sensitization in Vc itself. The experiments were carried out on urethan/alpha-chloralose anesthetized and immobilized rats. Single neurons were recorded and identified as nociceptive-specific (NS) in the deep laminae of Vc. During continuous saline superfusion (0.6 ml/h it) over the caudal medulla, Vc neuronal central sensitization was readily induced by mustard oil application to the tooth pulp. However, this mustard-oil-induced central sensitization could be completely blocked by continuous intrathecal superfusion of the wide-spectrum P2X receptor antagonist pyridoxal-phosphate-6-azophenyl-2, 4-disulphonic acid tetra-sodium (33-100 microM) and by apyrase (an ectonucleotidase enzyme, 30 units/ml). Superfusion of the selective P2X1, P2X3 and P2X(2/3) receptor antagonist 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (6-638 microM) partially blocked the Vc central sensitization. The two P2X receptor antagonists did not significantly affect the baseline nociceptive properties of the Vc neurons. These findings implicate endogenous ATP as an important mediator contributing to the development of central sensitization in nociceptive neurons of the deep laminae of the dorsal horn.
authors.affiliation: Faculty of Dentistry, University of Toronto, 124 Edward St., Toronto, ON M5G 1G6, Canada.
authors.forename: C Y
authors.initials: CY
authors.lastname: Chiang
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: Y F
authors.initials: YF
authors.lastname: Xie
authors.forename: J W
authors.initials: JW
authors.lastname: Hu
authors.forename: J O
authors.initials: JO
authors.lastname: Dostrovsky
authors.forename: M W
authors.initials: MW
authors.lastname: Salter
authors.forename: B J
authors.initials: BJ
authors.lastname: Sessle
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D001931:Brain Mapping; D004347:Drug Interactions; D008297:Male; D009149:Mustard Plant; D009474:Neurons / Q000187:drug effects* / Q000528:radiation effects; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D010812:Physical Stimulation / Q000379:methods; D010936:Plant Extracts / Q000494:pharmacology*; D010938:Plant Oils; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012684:Sensory Thresholds / Q000187:drug effects / Q000528:radiation effects; D013268:Stimulation, Chemical; D014275:Trigeminal Caudal Nucleus / Q000166:cytology*
chemical_list: D010936:Plant Extracts; D010938:Plant Oils; D010975:Platelet Aggregation Inhibitors; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D001081:Apyrase; C027793:mustard oil