Astroglial glutamate-glutamine shuttle is involved in central sensitization of nociceptive neurons in rat medullary dorsal horn.
Growing evidence suggests that astroglia are involved in pain states, but no studies have tested their possible involvement in modulating the activity of nociceptive neurons per se. This study has demonstrated that the central sensitization induced in functionally identified nociceptive neurons in trigeminal subnucleus caudalis (the medullary dorsal horn) by application of an inflammatory irritant to the rat's tooth pulp can be significantly attenuated by continuous intrathecal superfusion of methionine sulfoximine (MSO; 0.1 mM), an inhibitor of the astroglial enzyme glutamine synthetase that is involved in the glutamate-glutamine shuttle. Simultaneous superfusion of MSO and glutamine (0.25 mM) restored the irritant-induced central sensitization. In control experiments, superfusion of either MSO or glutamine alone, or vehicle, did not produce any significant changes in neuronal properties. These findings suggest that the astroglial glutamate-glutamine shuttle is essential for the initiation of inflammation-induced central sensitization but that inhibition of astroglial function may not affect normal nociceptive processing.
Chiang
Chen-Yu
CY
Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada M5G 1G6.
Wang
Jing
J
Xie
Yu-Feng
YF
Zhang
Sun
S
Hu
James W
JW
Dostrovsky
Jonathan O
JO
Sessle
Barry J
BJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000704:Analysis of Variance; D000818:Animals; D003782:Dental Pulp / Q000294:innervation; D004347:Drug Interactions; D005973:Glutamine / Q000378:metabolism* / Q000494:pharmacology; D017879:Isothiocyanates / Q000009:adverse effects; D008297:Male; D008717:Methionine Sulfoximine / Q000494:pharmacology; D009475:Neurons, Afferent / Q000145:classification / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014275:Trigeminal Caudal Nucleus / Q000166:cytology*
D017879:Isothiocyanates; D005973:Glutamine; D008717:Methionine Sulfoximine; C004471:allyl isothiocyanate
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