The Journal of Neuroscience, August 22, 2007, 27(34):9068-9076; doi:10.1523/JNEUROSCI.2260-07.2007
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Behavioral/Systems/Cognitive
Astroglial Glutamate–Glutamine Shuttle Is Involved in Central Sensitization of Nociceptive Neurons in Rat Medullary Dorsal Horn
Chen-Yu Chiang,1 *
Jing Wang,1 *
Yu-Feng Xie,1
Sun Zhang,1
James W. Hu,1
Jonathan O. Dostrovsky,2 and
Barry J. Sessle1,2
1Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada M5G 1G6, and 2Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8
Correspondence should be addressed to Dr. Barry J. Sessle, Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, Ontario, Canada M5G 1G6. Email: barry.sessle{at}utoronto.ca
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.
Key words: glutamine synthetase; methionine sulfoximine; trigeminal subnucleus caudalis; mustard oil; tooth pulp; inflammatory pain
Received May 17, 2007;
revised June 25, 2007;
accepted July 7, 2007.
Correspondence should be addressed to Dr. Barry J. Sessle, Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, Ontario, Canada M5G 1G6. Email: barry.sessle{at}utoronto.ca
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A. Okada-Ogawa, I. Suzuki, B. J. Sessle, C.-Y. Chiang, M. W. Salter, J. O. Dostrovsky, Y. Tsuboi, M. Kondo, J. Kitagawa, A. Kobayashi, et al.
Astroglia in Medullary Dorsal Horn (Trigeminal Spinal Subnucleus Caudalis) Are Involved in Trigeminal Neuropathic Pain Mechanisms
J. Neurosci.,
September 9, 2009;
29(36):
11161 - 11171.
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