PT  - JOURNAL ARTICLE
AU  - Chen-Yu Chiang
AU  - Jing Wang
AU  - Yu-Feng Xie
AU  - Sun Zhang
AU  - James W. Hu
AU  - Jonathan O. Dostrovsky
AU  - Barry J. Sessle
TI  - Astroglial Glutamate–Glutamine Shuttle Is Involved in Central Sensitization of Nociceptive Neurons in Rat Medullary Dorsal Horn
AID  - 10.1523/JNEUROSCI.2260-07.2007
DP  - 2007 Aug 22
TA  - The Journal of Neuroscience
PG  - 9068--9076
VI  - 27
IP  - 34
4099  - http://www.jneurosci.org/content/27/34/9068.short
4100  - http://www.jneurosci.org/content/27/34/9068.full
SO  - J. Neurosci.2007 Aug 22; 27
AB  - 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.