Glutamate receptor gene expression in spinal cord of arthritic rats.
Injury to peripheral tissue leads to hyperalgesia that appears to be partly mediated by functional changes at the level of the spinal cord. Glutamate receptors are thought to play a role in acute and short-term (minutes to hours) spinal cord nociceptive responses and may be involved in prolonged or chronic pain (hours to days). We used in situ hybridization to examine AMPA/kainate (GluR1, GluR2, and GluR3) and NMDA (NR1) receptor gene expression in spinal cord following induction of prolonged inflammation by a unilateral intraarticular injection of lipopolysaccharide (LPS; 10 micrograms) into the hindpaw. In control rats, GluR1 expression was prominent throughout the layers of the gray matter of the spinal cord. Microscopic examination revealed labeling of neuronal cell somata in all major nuclei. GluR2 was abundant in substantia gelatinosa and motor nuclei; emulsion-dipped sections exhibited intense labeling over densely packed neurons in the superficial laminae of dorsal horn and individual motoneurons of ventral horn. GluR3 and NR1 were expressed at low levels throughout spinal cord gray matter. One day after LPS injection, when joint swelling was maximal, GluR1 expression was bilaterally decreased by 25% in the substantia gelatinosa at the level of the lumbar cord. In contrast, no significant change was apparent in GluR2, GluR3, or NR1 expression in any nucleus of the cord. At 72 hr after injection, when joint diameter approached control values, all four transcripts were expressed at near control levels. These findings provide evidence for a specific decrease in GluR1 expression in the cord in response to joint inflammation.
Pellegrini-Giampietro
D E
DE
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461.
Fan
S
S
Ault
B
B
Miller
B E
BE
Zukin
R S
RS
D000818:Animals; D001168:Arthritis / Q000235:genetics* / Q000378:metabolism; D001345:Autoradiography; D005260:Female; D015870:Gene Expression; D017403:In Situ Hybridization; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017470:Receptors, Glutamate / Q000235:genetics* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology*
D012333:RNA, Messenger; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate