Involvement of ATP in noxious stimulus-evoked release of glutamate in rat medullary dorsal horn: a microdialysis study.
Our electrophysiological studies have shown that both purinergic and glutamatergic receptors are involved in central sensitization of nociceptive neurons in the medullary dorsal horn (MDH). Here we assessed the effects of intrathecal administration of apyrase (a nucleotide degrading enzyme of endogenous adenosine 5-triphosphate [ATP]), a combination of apyrase and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, an adenosine A1 receptor antagonist), or 2,3-O-2,4,6-trinitrophenyl-adenosine triphosphate (TNP-ATP, a P2X1, P2X3, P2X2/3 receptor antagonist) on the release of glutamate in the rat MDH evoked by application of mustard oil (MO) to the molar tooth pulp. In vivo microdialysis was used to dialyse the MDH every 5 min, and included 3 basal samples, 6 samples after drug treatment and 12 samples following application of MO. Tooth pulp application of MO induced a significant increase in glutamate release in the MDH. Superfusion of apyrase or TNP-ATP alone significantly reduced the MO-induced glutamate release in the MDH, as compared to vehicle. Furthermore, the suppressive effects of apyrase on glutamate release were reduced by combining it with DPCPX. This study demonstrates that application of an inflammatory irritant to the tooth pulp induces glutamate release in the rat MDH in vivo that may be reduced by processes involving endogenous ATP and adenosine.
Alan Edwards Centre for Research on Pain, Dept. of Anesthesia, McGill University, Montreal, QC H3G 1Y6, Canada.
Naresh
N
Kumar
Pavel S
PS
Cherkas
C Y
CY
Chiang
Jonathan O
JO
Dostrovsky
Barry J
BJ
Sessle
Terence J
TJ
Coderre
D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001081:Apyrase / Q000008:administration & dosage / Q000494:pharmacology; D059333:Central Nervous System Sensitization / Q000502:physiology*; D003782:Dental Pulp / Q000187:drug effects / Q000294:innervation; D018698:Glutamic Acid / Q000378:metabolism*; D007509:Irritants / Q000633:toxicity*; D008297:Male; D017551:Microdialysis; D008963:Molar; D009149:Mustard Plant / Q000633:toxicity*; D010938:Plant Oils / Q000633:toxicity*; D020671:Posterior Horn Cells / Q000378:metabolism*; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058469:Receptors, Purinergic P2X / Q000502:physiology; D014275:Trigeminal Caudal Nucleus / Q000503:physiopathology*; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology
D007509:Irritants; D010938:Plant Oils; D058920:Purinergic P2X Receptor Antagonists; D058469:Receptors, Purinergic P2X; D014970:Xanthines; D018698:Glutamic Acid; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D001081:Apyrase; D000241:Adenosine; C027793:mustard oil