EXPRESSION OF GAD MESSENGER-RNA IN SPINAL-CORD NEURONS OF NORMAL AND MONOARTHRITIC RATS

This study was carried out to investigate whether the increase of GABA levels in spinal cord dorsal horn in response to chronic inflammatory lesions results from an enhanced expression of the gene that governs the production of glutamate decarboxylase (GAD), the enzyme responsibl e for GABA synthesis. In situ hybridization was used to visualize neur ons expressing GAD mRNA within the spinal cord, in both intact rats an d in animals bearing chronic monoarthritis induced by intraarticular i njection of complete Freund's adjuvant. In control normal animals, neu ronal labeling by an antisense oligonucleotide probe occurred througho ut the spinal gray matter, except in the motoneuronal pool of Rexed's lamina IX. In treated animals 4 days after the induction of monoarthri tis, a significant increase in the number of labeled cells occurred in the superficial laminae (25.3%) and the neck (17.2%) of the ipsilater al dorsal horn at segments L(4)-L(5) which contain the projection doma in of the ankle joint. At 2 weeks, values were, respectively, 20.2% an d 13.9% over contralateral values, and an increase of 12.4% was found in the ventral horn. At 3 weeks, the ipsilateral increase of labeled c ells was restricted to the superficial dorsal horn (15.2%). These find ings emphasize the role played by the spinal GABAergic system in the m odulation of chronic nociceptive input. It is suggested that the respo nse of the spinal GABAergic system depends on the activation of GAD ge ne transcription in spinal neurons.