Journal
JOURNAL OF NEUROSCIENCE
Volume 27, Issue 34, Pages 9068-9076Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2260-07.2007
Keywords
glutamine synthetase; methionine sulfoximine; trigeminal subnucleus caudalis; mustard oil; tooth pulp; inflammatory pain
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Funding
- NIDCR NIH HHS [DE-04786, R01 DE004786] Funding Source: Medline
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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; 0.1mM), an inhibitor of the astroglial enzyme glutamine synthetase that is involved in the glutamate-glutamine shuttle. Simultaneous superfusion of MSO and glutamine (0.25mM) 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.
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