GLUTAMATE-RECEPTOR GENE-EXPRESSION IN SPINAL-CORD OF ARTHRITIC RATS

Injury to peripheral tissue leads to hyperalgesia that appears to be p artly 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 invol ved in prolonged or chronic pain (hours to days). We used in situ hybr idization to examine AMPA/kainate (GluR1, GluR2, and GluR3) and NMDA ( NR1) receptor gene expression in spinal cord following induction of pr olonged inflammation by a unilateral intraarticular injection of lipop olysaccharide (LPS; 10 mu g) into the hindpaw. In control rats, GluR1 expression was prominent throughout the layers of the gray matter of t he spinal cord. Microscopic examination revealed labeling of neuronal cell somata in all major nuclei. GluR2 was abundant in substantia gela tinosa and motor nuclei; emulsion-dipped sections exhibited intense la beling over densely packed neurons in the superficial laminae of dorsa l horn and individual motoneurons of ventral horn. GluR3 and NR1 were expressed at low levels throughout spinal cord gray matter. One day af ter LPS injection, when joint swelling was maximal, GluR1 expression w as bilaterally decreased by 25% in the substantia gelatinosa at the le vel of the lumbar cord. In contrast, no significant change was apparen t in GluR2, GluR3, or NR1 expression in any nucleus of the cord. At 72 hr after injection, when joint diameter approached control values, al l four transcripts were expressed at near control levels. These findin gs provide evidence for a specific decrease in GluR1 expression in the cord in response to joint inflammation.